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Background Management of single small hepatocellular carcinoma (HCC) is straightforward with curative outcomes achieved by locoregional therapy or resection. Liver transplantation is often considered for multiple small or single large HCC. Management of two small HCC whether presenting synchronously or sequentially is less clear. Aim To define the outcomes of patients presenting with two small HCC. Methods Retrospective review of HCC databases from multiple institutions of patients with either two synchronous or sequential HCC ≤ 3 cm between January 2000 and March 2018. Primary outcomes were overall survival (OS) and transplant-free survival (TFS). Results 104 patients were identified (male n = 89). Median age was 63 years (interquartile range 58-67.75) and the most common aetiology of liver disease was hepatitis C (40.4%). 59 (56.7%) had synchronous HCC and 45 (43.3%) had sequential. 36 patients died (34.6%) and 25 were transplanted (24.0%). 1, 3 and 5-year OS was 93.0%, 66.1% and 62.3% and 5-year post-transplant survival was 95.8%. 1, 3 and 5-year TFS was 82.1%, 45.85% and 37.8%. When synchronous and sequential groups were compared, OS (1,3 and 5 year synchronous 91.3%, 63.8%, 61.1%, sequential 95.3%, 69.5%, 64.6%, P = 0.41) was similar but TFS was higher in the sequential group (1,3 and 5 year synchronous 68.5%, 37.3% and 29.7%, sequential 93.2%, 56.6%, 48.5%, P = 0.02) though this difference did not remain during multivariate analysis. Conclusion TFS in patients presenting with two HCC ≤ 3 cm is poor regardless of the timing of the second tumor. All patients presenting with two small HCC should be considered for transplantation.

INTRODUCTION: Non‐alcoholic fatty liver disease (NAFLD) is a growing public health issue. Non‐invasive methods to assess the fibrosis stage are limited, and biopsy remains the gold standard. The objective of our study was to assess whether the portal venous pulsatility index (VPI) can be used as a predictor of high‐risk NAFLD at a tertiary referral centre for liver transplantation. METHODS: We retrospectively reviewed patients with biopsy‐proved NAFLD who had undergone a liver ultrasound scan within 1 year of biopsy at our centre from 2011 to 2019. RESULTS: We did not find a significant correlation between the VPI and the NAFLD risk category or correlation between the VPI and degree of steatosis (P > 0.05 for both). CONCLUSION: Since VPI can be easily obtained on routine liver ultrasound and since other studies do report a positive association with significant fibrosis, more studies are needed before it can be recommended or not in risk‐stratifying NAFLD patients into high‐ vs. low‐risk NAFLD.

Allogeneic hematopoietic cell transplantation (allo-HCT) is potentially curative for certain hematologic malignancies and nonmalignant diseases. The field of allo-HCT has witnessed significant advances, including broadening indications for transplantation, availability of alternative donor sources, less toxic preparative regimens, new cell manipulation techniques, and novel GVHD prevention methods, all of which have expanded the applicability of the procedure. These advances have led to clinical practice conundrums when applying traditional definitions of hematopoietic recovery, graft rejection, graft failure, poor graft function, and donor chimerism, because these may vary based on donor type, cell source, cell dose, primary disease, graft-versus-host disease (GVHD) prophylaxis, and conditioning intensity, among other variables. To address these contemporary challenges, we surveyed a panel of allo-HCT experts in an attempt to standardize these definitions. We analyzed survey responses from adult and pediatric transplantation physicians separately. Consensus was achieved for definitions of neutrophil and platelet recovery, graft rejection, graft failure, poor graft function, and donor chimerism, but not for delayed engraftment. Here we highlight the complexities associated with the management of mixed donor chimerism in malignant and nonmalignant hematologic diseases, which remains an area for future research. We recognize that there are multiple other specific, and at times complex, clinical scenarios for which clinical management must be individualized.

Background and Aims Currently used endoscopic items for the assessment of pouchitis and cuffitis have deficiencies in reliability and validation. We assessed the reliability and accuracy of new endoscopic items for pouchitis and of the Ulcerative Colitis Endoscopic Index of Severity [UCEIS] for cuffitis. Methods Three new endoscopic items were assessed and included in the Monash pouchitis endoscopic subscore: bleeding [absent/contact/spontaneous]; erosions [absent/ Results All three Monash endoscopic items had substantial intra-rater reliability with intraclass correlation coefficients [ICCs] >0.61 [95% CI >0.61], compared with only ulcers from the currently used PDAI endoscopic subscore, but inter-rater reliability was only substantial for ulceration and no better than those of the currently used endoscopic items. The Monash endoscopic subscore had a strong positive correlation with the reference standard global endoscopic lesion severity r = 0.80 [95% CI 0.80-0.80] and the reference standard PDAI endoscopic subscore r = 0.70 [95% CI 0.67–0.73], which was higher than the correlation observed for the currently used PDAI endoscopic subscore. The UCEIS had substantial intra-rater reliability, but only fair inter-rater reliability and poor diagnostic performance for cuffitis. Conclusions The Monash endoscopic items, and endoscopic subscore they generate, have enhanced overall performance compared with the currently used PDAI items and subscore. Further validation and responsiveness to change in disease state are indicated.

Digital image processing (DIP), is the use of a digital computer to process digital images through an algorithm. In this work DIP used to perform crack/defect Detection and geometry measurements in terms of angle, length, and width by building a MATLAB code. In this research, the test of tensile were applied on two flat samples, the two flat samples are painted in a speckle pattern on the tested surface to use DIP features. The DIP gives a low-cost optical, and an appropriate technique to detect crack/defect as well as geometry measurements with the load increment in terms of angle, length and width without any contact with the tested surfaces. The tests directed for both of flat Aluminum alloy and Copper alloy specimens. In order to guarantee the efficiency of the planned DIP systems, the comparison is considered between the test results of this technique with the measurements gained by actual physical by using calibrated digital vernier calliper (IP 54) to measure the length of the crack with 0-300 mm range and 0.01 mm resolution. The DIP obtained percentage of accuracy varies from (97) % to (99) % by comparison with the measurements gained by actual physical way. Conclusions Tensile tests have been carried out for two cracked/defected specimens. The tests applied for both flat Aluminum alloy and Copper alloy plates. The DIP percentage of accuracy differs from (97) % to (99) % by comparing with the actual physical measurements. The DIP technique can be developed in Structural Research laboratories, and make it possible to perform and work with the fatigue testing and/or crack propagation without human surveillance. The measuring of crack geometry can be easily used by the developed program, it just needs an operator who is familiar with this kind of testing. DIP had successfully used in the determination of the actual crack position, and it allows us to measure the actual length, width, and angle of the crack/defect. For quick and reliable surface defect inspection, the DIP program for crack detection is effective technique using instead of the slower traditional human inspection method. Automatic crack detection is very useful for Non-destructive testing (NDT). By manual investigation, it is hard to evaluate deterioration accurately [24]. The automatic crack detection can be implemented using some of the NDT procedures like (i) Radiographic, (ii) Ultrasonic (UT), (iii) Laser, and (iv) Infrared and thermal.

Polypharmacy, usually defined as taking ≥5 prescribed medications, increases chances of drug–drug interactions and toxicities, and may harm cancer patients who need multiple chemotherapeutic agents and supportive medications. We analyzed the effects of polypharmacy in overall survival (OS) in acute myeloid leukemia (AML). A total of 399 patients were divided into two groups: patients with polypharmacy (≥5 medications) versus without polypharmacy (

BACKGROUND: The role of obesity in prognosis of acute myeloid leukemia(AML) is debatable. Our retrospective study aimed to determine the effect of obesity on overall survival(OS) in AML. METHODS: AML patients diagnosed at University of Nebraska Medical Center were divided into 3-groups based on body mass index (BMI): normal(18.5-25kg/m(2)) or underweight(

Saudi Arabia has developed Saudi Vision 2030, an ambitious plan to reduce the country’s dependence on oil by supporting promising private energy organizations and by developing opportunities that contributes to the national economy. In the manufacturing sector, the government is encouraging technology transfers in the renewable energy industries. It is expected to result in the localization of significant parts of the renewable energy value chain in Saudi Arabia. Solar energy systems are proven renewable energy source globally and domestically, it has its long and vast share of experience, from operations and maintenance, to solar data monitoring and gathering. Wide areas had been identified, where this technology can be highly installed and integrated. Components can be manufactured from locally available raw materials to achieve the final products. This study analyzed the key elements of the value chain for producing crystalline silicon solar photovoltaic systems. This paper presents recommendations for localizing this industry in the Kingdom of Saudi Arabia to align with the goals of Saudi Vision 2030. Although these recommendations are based on the environmental conditions of Saudi Arabia, such are also highly relevant for further application to other countries in the Middle East and North Africa region, where widespread energy transitions from fossil fuels to renewable resources are already taking place.

A delicate analysis of the natural frequencies and mode shapes of a cable stayed bridge is essential to the solution of its dynamic responses due to seismic, wind and traffic loads. In this paper, a bridge with geometry comparable to the Quincy Bayview Bridge was modelled in order to explore the significance of the three dimensional and free vibration analysis. This paper provides a detail of the bridge and the equivalent cross section of the three-dimensional finite element model implicating cables, the bridge deck and pylons as well as the boundary conditions and free vibration analysis by Ansys15.0. The bridge was analyzed to free vibration to obtaine the natural frequency and mode shape. result of this paper present the natural frequencies and mode shapes of the bridge. The method of modelling cables is also studied. It is found that modelling cables as multi beam elements provides better results than using the traditional (and simpler) method of modeling them as single tensile elements.

Idiopathic pouchitis is the most common complication of ileal pouch–anal anastomosis, affecting up to 50–60% of ulcerative colitis pouch patients and 15–22% of familial adenomatous polyposis pouch ...

Background and Aims In symptomatic patients with ileoanal pouches, pouchoscopy is needed for accurate diagnosis but is invasive. We aimed to assess the utility of non-invasive gastrointestinal ultrasound and faecal calprotectin in ileoanal pouch patients. Methods Patients with an ileoanal pouch were consecutively enrolled in this cross-sectional study from clinics in Victoria, Australia. The pouchitis disease activity index was used as a reference standard. Video-recorded pouchoscopies were reviewed by three gastroenterologists. Pouch, pre-pouch, and cuff biopsies were reviewed by a single pathologist. Ultrasound was performed by a single gastroenterologist transabdominally and transperineally. Faecal calprotectin was measured from morning stool samples. All examiners were blinded to patients’ clinical history. Results A total of 44 participants had a pouchoscopy, of whom 43 had a faecal calprotectin test and 42 had an ultrasound; 17 had pouchitis, 15 had pre-pouch ileitis, and 16 had cuffitis. Pouch wall thickness of Conclusions Faecal calprotectin and ultrasound are accurate and complementary tests to diagnose and localise inflammation of the ileoanal pouch. Prospective studies are needed to validate proposed sonographic indices and calprotectin levels.

BackgroundMetastatic human epidermal growth receptor II (HER2) negative breast cancer remains incurable. Our phase I study showed that anti-CD3 × anti-HER2 bispecific antibody armed activated T cells (HER2 BATs) may be effective against HER2-tumors. This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor positive (HR+) and triple negative breast cancer (TNBC) as immune consolidation after chemotherapy. The primary objective of this study was to increase the traditional median time to progression after failure of first-line therapy of 2–4 months with the secondary endpoints of increasing overall survival (OS) and immune responses.MethodsHER2- metastatic breast cancer (MBC) patients received 3 weekly infusions of HER2 BATs and a boost after 12 weeks.ResultsThis phase II study included 24 HER2-HR+ and 8 TNBC patients who received a mean of 3.75 and 2.4 lines of prior chemotherapy, respectively. Eight of 32 evaluable patients were stable at 4 months after the first infusion. There were no dose limiting toxicities. Tumor markers decreased in 13 of 23 (56.5%) patients who had tumor markers. The median OS was 13.1 (95% CI 8.6 to 17.4), 15.2 (95% CI 8.6 to 19.8), and 12.3 (95% CI 2.1 to 17.8) months for the entire group, HER2-HR+, and TNBC patients, respectively. Median OS for patients with chemotherapy-sensitive and chemotherapy-resistant disease after chemotherapy was 14.6 (9.6–21.8) and 8.6 (3.3–17.3) months, respectively. There were statistically significant increases in interferon-γ immunospots, Th1 cytokines, Th2 cytokines, and chemokines after HER2 BATs infusions.ConclusionsIn heavily pretreated HER2-patients, immune consolidation with HER2 BATs after chemotherapy appears to increase the proportion of patients who were stable at 4 months and the median OS for both groups as well as increased adaptive and innate antitumor responses. Future studies combining HER2 BATs with checkpoint inhibitors or other immunomodulators may improve clinical outcomes.

Background: Patients ≥55 years of age with high-risk acute myeloid leukemia (AML) may benefit from an allogeneic hematopoietic cell transplantation (HCT), which is often the only potentially curative therapy available. However, complete remission (CR) is usually a pre-requisite for most centers to perform HCT, as CR predicts an optimal outcome. Many older patients with relapsed/refractory (R/R) AML are not transplanted as they do not achieve the required CR. In addition, due to their advanced age, they are unable to tolerate the myeloablative conditioning required for eradication of disease, while the more tolerable reduced intensity conditioning often exhibits high rates of relapse. The SIERRA trial is a prospective, randomized, phase 3 trial for older patients with R/R AML to address this unmet need. We hypothesized that a targeted delivery of radiation to the marrow, achieved with a limit of 24 Gray (Gy) radiation dose to the liver, via an infusion of a therapeutic dose of Iomab-B enables successful engraftment despite active disease in the marrow. Methods: Eligible patients were ≥55 years with active R/R AML (≥5% blasts), adequate organ function, and related/unrelated 8/8 HLA-matched donors. Patients were randomized (1:1) to the Iomab-B or Conventional Care (CC) arm. Patients randomized to Iomab-B received an outpatient dosimetric dose of Iomab-B followed by nuclear medicine imaging to determine the personalized therapeutic dose that would deliver radiation to the marrow while limiting the delivery of radiation to the liver to 24 Gy. HCT is performed 12-14 days following the infusion of a therapeutic dose of Iomab-B, and a non-myeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and low-dose Total Body Irradiation (TBI 2 Gy x 1 dose). Patients on the CC arm received investigator's choice of salvage therapy, including newly approved targeted agents, and could proceed to physician's choice of conditioning and HCT if they achieved CR. If CC patients did not achieve CR, the study allowed them to cross-over and receive Iomab-B-based conditioning followed by allogeneic HCT. Results: Preliminary data were available from 106 patients (Table 1). 53 patients (median age 64) were randomized to Iomab-B and received allogeneic transplant. All Iomab-B patients engrafted, despite a pre-therapy median of 26% marrow blasts. After randomization, 83% (44/53) CC patients failed salvage therapy, including 45% (24/53) who received targeted agents. 26 of 44 (60%) CC patients, with a median 33% marrow blasts, crossed over and received Iomab-B followed by allogeneic HCT. Patient age, donor type (MRD, MUD), bone marrow cellularity, blast percentage, type of donor, stem cell dose, administered Iomab-B activity (mCi), and absorbed radiation dose to the marrow (Gy), were analyzed for time to engraftment among each group. Median time to neutrophil and platelet engraftment were 14 days (range 9-22) and 17 days (range 4-39) respectively, with 91% of evaluable patients achieving full donor chimerism (>95% by day 100, Table 1). Neither the radiation dose delivered to the marrow (median 14.7 Gy; range, 4.6-32 Gy; Table 1) nor the total administered activity (median 632 mCi; range, 354-1027 mCi) showed correlation with the time to either neutrophil (p value=0.525) or platelet engraftment (p value=0.952). Regression analyses, considering all of the variables individually, did not indicate a statistically significant correlation (p > 0.1) between days to engraftment and radiation dose delivered to the marrow. These results were consistent for the Iomab-B cross-over group as well. Furthermore, the marrow absorbed dose did not show a significant correlation with % chimerism at day 28 in patients on the Iomab-B arm or in cross-over patients. Conclusion: Dosimetry to determine a patient-specific therapeutic dose of Iomab-B of 24 Gy to the liver provided absorbed marrow radiation doses that allowed for reliable engraftment after allogeneic HCT in older patients with R/R AML, despite a heavy leukemia burden with median bone marrow blasts of 26% prior to HCT (Iomab-B arm). There was no relationship between total administered activity or radiation dose delivered to the marrow with the speed of engraftment. The SIERRA trial is currently enrolling patients (www.sierratrial.com or clinicaltrials.gov NCT02665065). Disclosures Gyurkocza: Actinium: Research Funding. Nath:Daiichi Sankyo: Consultancy, Honoraria; Actinium: Consultancy, Honoraria; Astellas: Consultancy, Honoraria. Stiff:Kite, a Gilead Company: Research Funding; Gamida Cell: Research Funding; Atara: Research Funding; Unum: Research Funding; Macrogenics: Research Funding; Delta-Fly: Research Funding; Amgen: Research Funding. Hari:Takeda: Consultancy; BMS: Consultancy; GSK: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Incyte Corporation: Consultancy. Al-Kadhimi:Actinium Pharmaceuticals Inc.: Research Funding; Genzyme: Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Gilead Science: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Novavax: Current equity holder in publicly-traded company. Abboud:BMS: Current equity holder in publicly-traded company; AbbVie Inc: Current equity holder in publicly-traded company; Forty Seven Inc: Research Funding; Abbott Labs: Current equity holder in publicly-traded company; AlloVir: Research Funding; Ryvu: Research Funding; Actinium Pharmaceuticals Inc.: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; Pfizer: Research Funding. Magalhaes-Silverman:Incyte: Research Funding; Kadmon Holdings: Research Funding; Actinium Pharmaceuticals: Research Funding. Foran:BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding; Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; Revolution Medicine: Consultancy; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Schuster:Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Takeda, Genentech,, Seattle Genetics: Other: Personal Fees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Jazz: Consultancy; Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board. Levy:Karyopharm: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Research Funding, Speakers Bureau; Baylor University Med Center: Current Employment. Giralt:ACTINUUM: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; KITE: Consultancy; TAKEDA: Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria; AMGEN: Consultancy, Research Funding; OMEROS: Consultancy, Honoraria; NOVARTIS: Consultancy, Honoraria, Research Funding. Liang:Actinium Pharmaceuticals: Current Employment. Berger:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company. Reddy:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company.

Introduction Hepatic steatosis is a relatively common incidental finding on computed tomography (CT) studies performed for patients in the emergency department (ED). The aim of our survey was to explore the preferences and perspectives of emergency physicians regarding reporting of incidental findings with a focus on hepatic steatosis. Methods A prospective web-based questionnaire was conducted and distributed electronically to emergency clinicians with anonymous collection of responses. Results A total of 236 responses were received. The true response rate could not be determined due to different methods of electronic distribution. However, there was an estimated representation of 8.3% for ED physicians and 2.5% for trainees. The median time spent on the survey was less than 3 minutes. Seventy-seven per cent answered yes to giving an incidental finding more significance if mentioned in the conclusion section. More than half of respondents (60.2%) reported that they would like hepatic steatosis to be mentioned in a CT report while 30% reported that it was irrelevant in the emergency setting and 10% reported that they did not want it mentioned in the report. The majority (83.1%) reported that they would include this finding in the discharge summary for GP follow-up and less than half (44.1%) would mention it to patients. Conclusion Our survey highlights the importance of clear communication between radiologists and ED physicians when incidental findings are encountered. Radiologists play an important role in alerting ED physicians and clinicians who have access to patients' radiology reports to the presence of incidental findings including hepatic steatosis.

The overtime is an extra effort to ensure that the job or duty is completed. In private universities, overtime is needed to cover all hours of the courses and this may affect in a good or bad way on the lecture "depending on the number of extra hours". This research highlights the importance of overtime and how it affects the performance of private universities. The (SPSS) program has been used to analyze the data. 34 questionnaire papers were obtained out of 40 have been distributed on employees at Knowledge University. The study found that there is a strong relationship between employees' Productivity and factors (Wages, Environment and Health, Job content and IT skill). Moreover, there is a weak relationship between Employees' Productivity and factors (Work Arrangement, Stress–Satisfaction).

Aim: This study evaluated the overall survival (OS) of older patients (≥60 years) with acute myeloid leukemia based on the intensity of treatment. Methods: This single center, retrospective study included 211 patients diagnosed between 2000 and 2016, who received 10-day decitabine, low-intensity therapy or high-intensity therapy. Cox regression examined the impact of therapy on OS. Results: Younger patients were more likely to receive high-intensity therapy. Patients who received low-intensity therapy had worse OS compared with high-intensity therapy (median OS: 1.2 vs 8.5 months; p

This paper discusses and presents the implementation of a boost converter as power electronic interface to be used with the thermoelectric generator (TEG). The common application for such system is the battery charger. The boundary conditions for battery chargers include the charging current and battery voltage limits which have to be respected throughout the charging process, while the maximization of the power generated from the TEG is a global target that is desired to be met as much as possible. Coordinated control algorithm that collectively combines these constraints is the main focus of this work. Novel global control algorithm is proposed and verified in this paper with detailed analysis that shows the effectiveness of the proposed algorithm. Dual control loops for the voltage and current of the boost converter will be designed and analyzed to satisfy the source and load demands. Maximum power point tracking (MPPT) mode, power matching mode and voltage stabilization mode will be integrated in the control algorithm of the battery charger. This paper puts a schematic design for a system that harvests energy from a thermoelectric generator bank of a TEG1-12611-6.0 TEG modules in order to charge a battery bank of Samsung ICR18650 Batteries using constant current (CC) and constant voltage (CV) charging profiles.

Introduction Older adults with acute myeloid leukemia (AML) often have significant comorbidities. We hypothesized that greater comorbidity burden predicts worse 1-month mortality and overall survival (OS) in patients ≥60 years with AML. Materials and methods We included 50,668 patients ≥60 years diagnosed between 2004 and 2014 from the National Cancer Database; patients were divided into 3 groups with Charlson comorbidity index (CCI) 0, 1, and ≥2. Chi-square tests were used to examine the association between CCI and different variables. We used logistic regression and Cox proportional hazard models to determine predictors of 1-month mortality and OS, respectively. Results Among the entire cohort, 65% had CCI 0, 24% had CCI 1, and 11% had CCI ≥2. Thirty-four percent did not receive chemotherapy. Patients with CCI 0 were more likely to receive chemotherapy, especially multiagent chemotherapy and undergo upfront hematopoietic cell transplantation. In multivariate analyses, 1-month mortality and OS were significantly worse with CCI 1 or ≥2, compared with CCI 0 in the entire cohort, as the subgroup of only those patients who received chemotherapy. Younger age, male gender, higher annual income, academic facility, longer travel distance, and acute promyelocytic leukemia were associated with improved OS. Conclusion In one of the largest real-world studies of older adults with AML, we demonstrated that greater comorbidity, measured by higher CCI, independently predicted worse early mortality and OS in older patients with AML. Higher CCI was more common with increasing age and correlated with lower likelihood of receiving chemotherapy and hematopoietic cell transplantation. Whether optimal comorbidity management and supportive care may improve outcomes needs to be studied further.

A convolution neural network (CNN) uses kernels to filter applied images. These kernels learn their coefficients' values during the training process, thus they do not possess any centrosymmetry. Hence, the phase responses for these kernels are neither zero-phase nor linear-phase. This technique adds a group delay distortion to the filtered images. In this paper, we constrain the values of the kernels' coefficients to be centrosymmetric. This scheme guarantees the prevention of any distortion in the filtered images. In the proposed method, the CNN trains all the kernel coefficients as normal. Then every two-centrosymmetric coefficients are set to their average. This does not affect much the accuracy of the CNN. The proposed algorithm may be used to improve images generated using generative adversarial networks (GAN), autoencoders, image segmentation, and all other algorithms that generate images or video using CNN. This point still requires further study.

Quality of life after ileal pouch-anal anastomosis (IPAA) surgery is generally good. However, patients can be troubled by pouch-related symptoms and pouch disorders that can be inflammatory, mechanical/surgical, and functional. Management of patients with IPAA begins with measures to maintain a healthy pouch such as optimizing pouch function, providing tailored advice on a healthy diet and lifestyle, screening for and addressing metabolic complications of IPAA, pouch surveillance, and risk stratification for risk of pouchitis and pouch failure. Pouchitis is the most common inflammatory disorder. Primary pouchitis is a spectrum currently classified into three progressive phases-an antibiotic-responsive, an antibiotic-dependent, and an antibiotic-refractory phase. It is predominately microbially mediated in acute antibiotic-responsive pouchitis and predominately immune mediated in chronic antibiotic-refractory pouchitis (CARP). Secondary prophylaxis is recommended for recurrent antibiotic-responsive and for antibiotic-dependent pouchitis. Secondary causes of antibiotic-refractory pouchitis should be ruled out before a diagnosis of CARP is made. CARP is best classified as primary sclerosing cholangitis associated, immunoglobulin G4-associated, and autoimmune. Primary sclerosing cholangitis-associated CARP can be treated with budesonide or oral vancomycin. Early recognition of immunoglobulin G4-associated pouchitis minimizes ineffective antibiotic use. Autoimmune CARP can be managed in a manner similar to UC. The current place of immunosuppressives in the treatment algorithm depends on availability and early access to biological agents. Vedolizumab and ustekinumab are the preferred first- and second-line biologics for autoimmune CARP owing to their efficacy, better side effect profile, and low immunogenicity and need for concomitant immunomodulatory therapy. Antitumor necrosis factor should be reserved for autoimmune CARP failing the above and for CD of the pouch. There are no guidelines for the surveillance of pouches for dysplasia. Incidence varies based on a patient's risk. Since incidence is low, a risk-stratified approach is recommended.

Background and aims Limitations to the use of long-term Hepatitis B Immunoglobulin (HBIg) following liver transplantation for hepatitis B (HBV) have led to the substitution of HBIg with oral nucleo(s)tide analogue prophylaxis. We prospectively assessed the long-term safety and efficacy of switching to tenofovir disoproxil fumarate (TDF) from HBIg. Methods An open-label, multicenter switch study was conducted to evaluate the substitution of TDF for HBIg whilst continuing lamivudine (LAM) therapy in preventing the recurrence of HBV in patients who had been maintained as hepatitis B surface antigen (HBsAg)-negative posttransplantation for at least 12 months. Results Eighteen patients were enrolled (median age 66 years, range 42-78 years); 84% were male, and 78% on calcineurin inhibitors. Median time after transplantation was 14 years (range 5-19), and median duration of HBIg/LAM prior to the switch was 10 years (range 1-14). Median follow-up was 5 years (range 5-8). Of 18 patients, 16 (89%) remained HBsAg and HBV DNA negative at the end of follow-up. Two patients had re-emergence of HBsAg without a detectable HBV DNA and no clinical sequelae. Creatinine clearance significantly reduced (median 59 mL/min to 51 mL/min, P = 0.03), necessitating dose reduction of TDF in six (33%) participants, with two eventually ceasing TDF. One patient switched back to HBIg by choice. All patients who changed therapy maintained an undetectable HBsAg. Conclusion Substitution of HBIg with TDF in patients on LAM is well tolerated and effective for the long-term prevention of HBV recurrence posttransplantation. Renal dysfunction occurs frequently in the posttransplant setting and can require dose adjustment of TDF or change of therapy.

This study reviews theories and models on operational and strategic risk management, as well as the main frameworks and regulations on risk management. The study focused on Cihan banks and the results were conclusive that risk management impact on Cihan bank and the factors affecting on banks is a committee, board, Chief executive officer (CEO). We distributing 70 questioners and obtain 50 only. The results and findings of this research are analyzed by SPSS package version 21 to build analysis and draw a conclusion. The research findings showed a distinctive relation between measuring dimensions and risk management.

Background: Several targeted therapies have been recently approved as treatment options for acute myeloid leukemia (AML), however, complete remissions (CR) in relapsed/refractory (R/R) patients remain low. Due to suboptimal responses to standard therapies, most of these patients do not receive an allogeneic hematopoietic cell transplant (HCT). In addition, AML patients ≥55 years have poor tolerance and high morbidity from a myeloablative HCT. The SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) has been investigating the use of Iomab-B, an 131I-labeled anti-CD45 monoclonal antibody, to reduce relapse in patients with active, R/R AML who receive HCT as compared to Conventional Care (CC) therapies. With the recent approval of various targeted therapies like BCL-2 inhibitors (e.g., venetoclax), FLT-3 inhibitors (e.g., midostaurin and gilteritinib) and IDH inhibitors (e.g., ivosidenib), the protocol was amended to include patients refractory to these therapies. We are reporting on the success rate of engraftment and tolerability of Iomab-B among the CC patients who cross-over to receive Iomab-B and HCT after failing these agents. Methods: Approximately 150 older patients with R/R AML are to be randomized (1:1) to receive Iomab-B followed by fludarabine, total body irradiation (2 Gy) and allogeneic HCT, or to conventional care (CC). CC patients receive physician's choice of therapy, including targeted therapies, and may proceed to standard of care allogeneic HCT if they achieve CR. CC patients not achieving CR may cross over to Iomab-B-based HCT. Results: Available data for 136 patients (>90% of target enrollment; median age 65) demonstrated they had a median of 3 (range: 1-7) prior lines of AML therapies. Median marrow blast at time of study entry was 25%. Prior to enrollment, 85 (63%) patients received targeted therapies, including BCL-2 inhibitors (62%), FLT-3 inhibitors (18%), IDH inhibitors (7%) and others (13%; e.g., gemtuzumab ozogamicin). Among the 50 evaluable patients in the Iomab-B group that received HCT, all successfully engrafted after a median radiation dose delivered to marrow of 14.7 Gy (range: 4.6 - 44.6) with a median time to neutrophil and platelet engraftment of 14.5 (range: 9-28) and 18 (range: 4-58) days, respectively. Of 63 patients randomized to the CC arm and with data available, 11 (17%) achieved CR and proceeded to standard of care HCT without Iomab-B while 52 (83%) did not respond to CC therapy. Twenty-seven of 63 (43%) CC patients received targeted therapy, of whom 21 received venetoclax with hypomethylating agents (HMA) or low-dose Cytarabine (LDAC). Seven of the 27 (26%) CC patients remission after targeted therapy and received standard of care HCT. Of the 20 patients who did not respond to targeted therapies, 11 (55%) crossed-over and received Iomab-B/HCT with a median radiation dose delivered to marrow of 18 Gy (range: 12.6 - 22.6). Median time to neutrophil and platelet engraftment was 12 (range: 10-27) and 20 (range: 15-38) days, respectively. Safety data are available for 103 transplanted patients in both groups and are presented in table. The incidence of Grade ≥3 febrile neutropenia (FN) was 37% vs 55%, sepsis 5% vs 30%, and mucositis 10% vs 20% in the Iomab-B group compared to all transplanted patients in the CC group. In patients who received targeted therapy and HCT (crossover or standard HCT), incidences of FN, sepsis and mucositis were 39%, 28% and 22%, respectively. Conclusion: SIERRA trial patients not achieving CR with recently approved targeted therapies who then crossed-over to receive HCT with Iomab-B successfully engrafted. Time to engraftment was similar to those who were randomized to receive Iomab-B and HCT. Available data suggest incidences of sepsis and mucositis are lower in the Iomab-B group. (www.sierratrial.com or clinicaltrials.gov NCT02665065) Figure 1 Figure 1. Disclosures Gyurkocza: Actinium Pharmaceutical Inc.: Research Funding. Nath: Actinium: Consultancy, Honoraria; Incyte: Consultancy, Honoraria. Litzow: Amgen: Research Funding; Biosight: Other: Data monitoring committee; Jazz: Other: Advisory Board; Pluristem: Research Funding; Astellas: Research Funding; Actinium: Research Funding; Omeros: Other: Advisory Board; AbbVie: Research Funding. Koshy: Astellas; Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium, Speakers Bureau. Stiff: Seagen: Research Funding; Incyte: Research Funding; Gamida Cell: Research Funding; Janssen: Research Funding; CRISPR Therapeutics: Consultancy, Honoraria; Kite, a Gilead Company: Research Funding; Macrogenics: Research Funding; Bristol Myers Squibb: Research Funding; Cellectar: Research Funding; BioLineRX: Research Funding; MorphoSys: Consultancy, Honoraria; Amgen: Research Funding; Karyopharm: Consultancy, Honoraria; Cellectar: Research Funding; Actinium: Research Funding. Abhyankar: Incyte/Therakos: Consultancy, Research Funding, Speakers Bureau. Hari: Karyopharm: Consultancy; Millenium: Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Celgene-BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding, Speakers Bureau. Chen: Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium. Sabloff: Novartis: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; TaiHo: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Jaxx: Membership on an entity's Board of Directors or advisory committees; ROCHE: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Orozco: Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium, Research Funding. Foran: abbvie: Research Funding; revolution medicine: Honoraria; novartis: Honoraria; certara: Honoraria; actinium: Research Funding; OncLive: Honoraria; aptose: Research Funding; trillium: Research Funding; gamida: Honoraria; takeda: Research Funding; boehringer ingelheim: Research Funding; bms: Honoraria; taiho: Honoraria; syros: Honoraria; sanofi aventis: Honoraria; pfizer: Honoraria; servier: Honoraria; kura: Research Funding; h3bioscience: Research Funding; aprea: Research Funding; sellas: Research Funding; stemline: Research Funding. Jamieson: Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium. Magalhaes-Silverman: Actinium Pharmaceuticals; Incyte; Marker Therapeutics: Other: Principal Investigator, SIERRA Trial, Actinium, Research Funding. Schuster: Takeda: Consultancy, Speakers Bureau; MorphoSys Ag: Consultancy, Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Intellisphere: Consultancy, Speakers Bureau; AbbVie Incorporated: Consultancy, Speakers Bureau; Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Epizyme: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Speakers Bureau; BeiGene: Consultancy, Speakers Bureau; Actinium Pharmaceuticals: Other: Principal Investigator, SIERRA Trial, Actinium Pharmaceuticals, Research Funding; Rafael Pharmaceuticals: Research Funding; GSK: Research Funding; AlloVir: Research Funding; Incyte: Research Funding; Seattle Genetics: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Genentech: Consultancy, Speakers Bureau; Amgen: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau; Celgene: Consultancy, Current equity holder in publicly-traded company, Speakers Bureau. Law: Actinium Pharmaceuticals: Research Funding; Novartis: Consultancy. Levy: Takeda, Celgene, Seattle Genetics, AbbVie, Jazz Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, Amgen, Spectrum Pharmaceuticals,Janssen.: Consultancy. Lazarus: Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees. Giralt: PFIZER: Membership on an entity's Board of Directors or advisory committees; AMGEN: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; SANOFI: Membership on an entity's Board of Directors or advisory committees; CELGENE: Membership on an entity's Board of Directors or advisory committees; JAZZ: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; JENSENN: Membership on an entity's Board of Directors or advisory committees; Actinnum: Membership on an entity's Board of Directors or advisory committees. Berger: Actinium Pharmaceuticals, Inc: Current Employment. Spross: Actinium Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Desai: Actinium Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Reddy: Actinium Pharmaceuticals: Current Employment, Current holder of stock options in a privately-held company. Pagel: AstraZeneca: Consultancy; MEI Pharma: Consultancy; Epizyme: Consultancy; Actinium Pharmaceuticals: Consultancy; Kite, a Gilead Company: Consultancy; BeiGene: Consultancy; Pharmacyclics/AbbVie: Consultancy; Gilead: Consultancy; Incyte/MorphoSys: Consultancy.

Background: Acute Lymphoblastic Leukemia (ALL) outcomes have significantly improved over time with multi-agent chemotherapy, and the addition of asparaginase (ASP) has demonstrated the ability to prolong overall survival. ASP has multiple toxicities, and it remains a challenge to manage them safely, particularly coagulopathy and thrombosis (30-40% based on historical studies). The best prophylactic anticoagulation strategy in patients with acute leukemias, particularly ALL with asparaginase use, remains unclear due to severe coexisting thrombocytopenia and coagulopathy. Though the current guidelines recommend using Antithrombin (AT) replacement or low molecular weight heparin (LMWH) for thrombosis prophylaxis, the evidence is weak with concerns of thrombosis (Blood (2020) 136 (3): 328-338) with the use of fibrinogen concentrates(cryoprecipitate) and limited efficacy data with AT replacement and unfractionated heparin (UFH) for thrombosis prophylaxis. Due to potential "resistance" to LMWH and UFH from acquired AT deficiency with ASP use, our institution in 2017 has adopted the use of the direct Xa inhibitor, Apixaban for thrombosis prophyalxis. We report the safety and effectiveness of Apixaban for thrombosis prophylaxis with ASP. Methods: In this retrospective study, we reviewed the data on 20 patients treated with ASP between 2017-2020. Thrombosis prophylaxis was instituted with Apixaban 2.5 mg PO Q 12 hourly for three weeks along with cryoprecipitate as needed for bleeding or fibrinogen levels Results: Among the 20 patients treated during this period, 18 (90%) had ALL, and 2(10%) had NK/T cell lymphoma. Of the patients with ALL, 67% had high risk and 33% with standard-risk ALL. The median age of this cohort was 29.5 years (range: 19-63 years), 80% were males, 70% white, 30% were Latino or Hispanic, median body mass index-BMI of 30.2 kg/m 2(19.4-40.7 kg/m 2) and 65% were non-smokers. The median baseline AT activity was 107% (79-221%), 95% used concurrent corticosteroids (65%- Prednisone, and 30% used Dexamethasone). The most common induction treatment was CALGB 10403 (55%). Of the total, 95% received pegylated ASP, and only one patient received Erwinia ASP due to prior history of anaphylaxis. The major toxicities attributed to ASP included 5% grade II and 15% grade III-IV aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation, 20% had bilirubin elevation, 10% developed grade III-IV acute pancreatitis, and 5% developed severe hypertriglyceridemia needing aphaeresis. Two patients (10%) developed thrombosis [catheter associated deep venous thrombosis (DVT) and one patient with lower extremity proximal DVT] within 4 weeks of use of ASP, with one of the two patients (5%) developing (lower extremity proximal DVT) while on being off anticoagulation due to bleeding. Major bleeding or CRNMB developed in 5% (spontaneous splenic rupture from ALL leading to hemorrhagic shock). The median number of cryoprecipitate units used per patient during weeks 1,2,3, and 4 was 5(0-35), 5(0-40), 5(0-15), 7.5(0-15), respectively; No patients received fresh frozen plasma or AT concentrates. Conclusions: With the use of Apixaban prophylaxis, the incidence of thrombosis was 10% within four weeks from ASP and 5% while on anticoagulation. The incidence of major bleeding or CRNMB was 5%. Hypofibrinogenemia, acquired AT deficiency due to ASP, was seen between days 7-21 after using ASP (figure 1 & 2) and recovered subsequently. This study demonstrates initial evidence of the safety and efficacy of Apixaban for thrombosis prophylaxis and cryoprecipitate infusions in patients treated with ASP. Figure 1 Figure 1. Disclosures Gundabolu: Samus Therapeutics: Research Funding; Pfizer: Research Funding; BioMarin Pharmaceuticals: Consultancy; Bristol-Myers Squibb Company: Consultancy; Blueprint Medicines: Consultancy. Bhatt: Jazz: Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Research Funding; Tolero Pharmaceuticals, Inc: Research Funding; National Marrow Donor Program: Research Funding; Abbvie: Consultancy, Research Funding; Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Partnership for health analytic research, LLC: Consultancy; Servier Pharmaceuticals LLC: Consultancy; Rigel: Consultancy. Vose: Kite, a Gilead Company: Honoraria, Research Funding. Lunning: Myeloid Therapeutics: Consultancy; Janssen: Consultancy; Kyowa Kirin: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy; Novartis: Consultancy; Celgene, a Bristol Myers Squibb Co.: Consultancy; AbbVie: Consultancy; TG Therapeutics: Consultancy; Daiichi-Sankyo: Consultancy; Legend: Consultancy; Kite, a Gilead Company: Consultancy; Verastem: Consultancy; Acrotech: Consultancy; Karyopharm: Consultancy; Spectrum: Consultancy; Beigene: Consultancy; Morphosys: Consultancy. Baljevic: BMS/Celgene: Consultancy; Oncopeptides: Other: Advisory Board; Janssen Research: Other: Advisory Board; Karyopharm: Other: Advisory Board; BMS/Celgene: Other: Advisory Board; Amgen: Research Funding; Exelixis: Research Funding. Ganti: Merck: Research Funding; Apexigen: Research Funding; Nektar: Research Funding; Top Alliance Biosceinces: Research Funding; Lovance: Research Funding; Novartis: Research Funding; WindMil Therapeitucs: Research Funding; Takeda: Research Funding; Flagship Biosciences: Consultancy; AstraZeneca: Consultancy, Other: Advisory Board; Mirati Therapeutics: Consultancy, Other: Advisory Board; G1 Therapeutics: Consultancy, Other: Advisory Board; Blueprint Medicines: Consultancy, Other: Advisory Board; Cardinal Health: Consultancy, Other: Advisory Board; Roche: Consultancy, Other: Advisory Board; YMabS Therapeutics: Other: DSMC Chair.

Background: Despite recently approved novel targeted therapies, most patients with high-risk acute myeloid leukemia (AML) still require allogeneic hematopoietic cell transplantation (HCT) to achieve long-term survival. However, older patients with relapsed/refractory (R/R) AML are often unable to undergo HCT due to the toxicity of myeloablative pre-conditioning. Since higher doses of chemotherapy and radiation are associated with prolonged myelosuppression or infectious complications, targeted radiotherapy with Iomab-B, employed in the SIERRA trial, was designed to minimize toxicities in a patient population unable to tolerate standard high-dose myeloablative HCT pre-conditioning. We hypothesize that Iomab-B, which spares non-hematologic organs such as the GI tract, exhibits a favorable toxicity profile with respect to mucositis, febrile neutropenia (FN), and sepsis. Methods: The SIERRA trial is a prospective trial for patients ≥55 years of age with R/R AML (≥5% blasts) and 8/8 HLA-matched related or unrelated donors. Patients were randomized (1:1) to Iomab-B or Conventional Care (CC). Those in the Iomab-B group received a dosimetric infusion of Iomab-B followed by nuclear imaging to determine the personalized therapeutic dose to be delivered to the bone marrow and to other sites of disease. Therapeutic dose calculations, utilizing the Olinda software (Version 2.1, Hermes Medical) to determine the delivery of a maximum of 24 Gray (Gy) dose to the liver, were performed based on the imaging results. HCT is performed 12-14 days following the infusion of a therapeutic dose of Iomab-B, and a non-myeloablative conditioning backbone of fludarabine (30 mg/m2 x 3) and low-dose Total Body Irradiation (TBI 2 Gy x 1 dose). CC patients received the investigator's choice of salvage therapy. Safety data was evaluated from randomization and up to 100 days after HCT in the patients randomized to the Iomab-B group. We specifically evaluated AE variables of mucositis (Gr 2-4), FN (Gr3,4) and sepsis. An analysis was performed with both total activity of Iomab-B as well as with the radiation dose delivered to the bone marrow, stomach wall, small and large intestinal walls. For each of the 3 AEs of interest, a multivariate analysis was performed, allowing each of the predictor variables to be included in the model. Results: A total of 106 patients were randomized at the time of analysis. For those randomized to Iomab-B, data is available for 45 patients that received a therapeutic dose of Iomab-B and HCT. The median dose of Iomab-B administered was 603 mCi (range 313-1027 mCi) and the median radiation dose delivered to the marrow in the Iomab-B group was 14.7 Gy (range 4.6 - 32 Gy). All patients (median age 64) treated with a therapeutic dose of Iomab-B achieved neutrophil engraftment after a median of 14 days post-HCT (range 9-22), despite presenting with a median 26% marrow blasts prior to initiation of therapy. Rates of mucositis, FN, and sepsis are shown in Table 1. No correlation between AEs (FN, mucositis, sepsis) and administered Iomab-B activity (p=0.08), nor with dose delivered to GI tract (p=0.09) was observed. Furthermore, these AEs were not related to the dose of radiation received by the small intestine (median 2.7 Gy range 1.1-6.8 Gy) large intestine (median 2.6 Gy range 0.9-6.5 Gy), nor an average of all 4 GI sites (median 2.8 Gy range 1.6-6.8 Gy). Conclusions: Unlike cases involving treatment with cytotoxic chemotherapy and external beam radiation where mucositis, infections and sepsis increase along with the administered dose, targeted myeloablative conditioning with Iomab-B resulted in low incidences of severe mucositis, FN, and sepsis. These AEs do not appear to be related to the total dose of Iomab-B administered nor to the specific radiation dose delivered to the bone marrow. Furthermore, a low dose of radiation (2.8 Gy) was received by the GI tract compared to the larger dose of radiation (14.7 Gy) delivered to the marrow. Taken together, these results represent potentially significant improvements in the safe delivery of myeloablative therapy with high-dose targeted radioimmunotherapy, prior to HCT in older patients with R/R AML. This SIERRA trial is currently enrolling patients (www.sierratrial.com or clinicaltrials.gov NCT02665065). Disclosures Gyurkocza: Actinium: Research Funding. Nath:Actinium: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria. Stiff:Kite, a Gilead Company: Research Funding; Gamida Cell: Research Funding; Atara: Research Funding; Unum: Research Funding; Delta-Fly: Research Funding; Macrogenics: Research Funding; Amgen: Research Funding. Hari:Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; BMS: Consultancy; Takeda: Consultancy; Incyte Corporation: Consultancy. Al-Kadhimi:Actinium Pharmaceuticals Inc.: Research Funding; Genzyme: Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Gilead Science: Current equity holder in publicly-traded company; Moderna: Current equity holder in publicly-traded company; Novavax: Current equity holder in publicly-traded company. Abboud:Ryvu: Research Funding; Actinium Pharmaceuticals Inc.: Research Funding; Pfizer: Research Funding; Johnson & Johnson: Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company; Abbott Labs: Current equity holder in publicly-traded company; AbbVie Inc: Current equity holder in publicly-traded company; AlloVir: Research Funding; Forty Seven Inc: Research Funding. Magalhaes-Silverman:Kadmon Holdings: Research Funding; Actinium Pharmaceuticals: Research Funding; Incyte: Research Funding. Foran:Xencor: Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy; Agios: Honoraria, Research Funding; H3Biosciences: Research Funding. Schuster:Amgen, Abbvie, Gilead, Takeda, Celgene, Pharmacyclics, Astellas, Verastem, Merck, Novartis, Takeda, Genentech,, Seattle Genetics: Other: Personal Fees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Kebriaei:Pfizer: Other: Served on advisory board; Kite: Other: Served on advisory board; Amgen: Other: Research Support; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Jazz: Consultancy. Levy:Karyopharm,Takeda, BMS: Consultancy, Honoraria, Speakers Bureau. Giralt:KITE: Consultancy; NOVARTIS: Consultancy, Honoraria, Research Funding; OMEROS: Consultancy, Honoraria; ACTINUUM: Consultancy, Research Funding; MILTENYI: Consultancy, Research Funding; TAKEDA: Research Funding; CELGENE: Consultancy, Honoraria, Research Funding; JAZZ: Consultancy, Honoraria; AMGEN: Consultancy, Research Funding. Liang:Actinium Pharmaceuticals: Current Employment. Berger:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company. Reddy:Actinium Pharmaceuticals Inc.: Current Employment, Current equity holder in publicly-traded company.

Background Patients with rel/ref AML have very few options, despite novel targeted therapies (e.g. venetoclax, IDH inhibitors), other than allogeneic hematopoietic cell transplantation (HCT) to achieve a durable CR. In addition, patients ≥55 years of age cannot tolerate multiple cycles of intensive therapy trying to achieve a CR prior to transplant. Older patients are also unable to tolerate more intense myeloablative conditioning. The SIERRA trial is a prospective, randomized, phase 3 trial addressing the unmet need to improve access of older patients with active, rel/ref AML to HCT, the only potentially curative therapy available to them. Methods Patients are randomized (1:1) to receive Iomab-B (day-12) followed by FLU/TBI and HCT, or to conventional care (CC). CC patients may receive investigator's choice of salvage therapy, including newly approved targeted agents and may proceed to standard HCT if they achieve CR. If patients do not achieve CR, the study allows cross-over (CO) to Iomab-B/HCT. Results Preliminary data are available from 75 (50%) patients (Table 1). Patients (median age 64) were heavily pretreated with 85% failing ≥2 induction therapies and 33% failing targeted therapies. All patients transplanted after Iomab-B engrafted. After randomization, 82% (31/38) patients in the CC arm failed salvage therapy, despite 32% (12/38) receiving targeted therapy. 73% (8/11) of the patients receiving venetoclax with HMA or LDAC did not achieve remission. Of the 31 patients, 9 were not CO transplant candidates. Of the 22 patients that crossed over for transplant, majority (91%, N=20) were able to receive Iomab-B/HCT, despite a median of 35% BM blasts. The most common reason preventing CO to transplant was disease progression. CC patients showed increased incidence of Grade 3 febrile neutropenia, compared to Iomab-B patients prior to CO or HCT (34% vs 8%). Iomab-B administration was generally well-tolerated with 1 Grade 3 and no Grade 4, infusion reaction. There were no Iomab-B-related deaths and 100-day non-relapse TRM was 3% on the Iomab-B arm (Table 1). Conclusion Despite advanced age, active disease and heavily pre-treated patients, 100% (31/31) of all patients in the Iomab-B arm who received treatment with Iomab-B were able to undergo HCT and successfully engrafted. In comparison, only 18% (7/38) of the patients on the CC arm achieved remission and underwent conventional HCT despite a high percentage receiving recently approved agents and targeted therapies. Overall, including patients crossing over to receive Iomab-B/HCT after failure of salvage therapy in the CC arm, 68% (51/75) of all patients enrolled in the trial underwent HCT after Iomab-B. These preliminary results represent significant improvements in the current rates of transplantation in this patient population. This SIERRA trial is currently enrolling (www.sierratrial.com or clinicaltrials.gov NCT02665065).

The third annual Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was held on November 29, 2018, at the American Society of Hematology (ASH) annual meeting. This workshop featured the latest research focused on minimal residual disease (MRD) assessment and immune profiling (IP) in myeloma as well as discussion of the statistical and regulatory issues intrinsic to the development of MRD as a surrogate endpoint. In this report, we provide a summary of the workshop and focus on the integration of MRD and IP assessment into trial design and clinical practice.

Erythropoietic protoporphyria (EPP) is an inherited metabolic disorder of heme synthesis resulting from overproduction of protoporphyrin IX (PPIX), which can lead to progressive liver disease characterized by recurrent EPP crises and end-stage liver disease. We used the Australian Transplant Registry to identify 5 patients referred for liver transplantation between 2008 and 2017. A total of 4 patients had EPP secondary to ferrochelatase deficiency, and 1 patient had X-linked EPP. No patient had follow-up with a specialist prior to the diagnosis of progressive liver disease. There were 3 patients who underwent orthotopic liver transplantation, whereas 2 died while on the transplant waiting list. Parenteral PPIX-lowering therapy was used in 4 patients and was effective in 3 patients, although 2 of these had rebound porphyria and worsening liver function following a decrease in the intensity of therapy. Early disease recurrence in the allograft following transplantation occurred in 2 patients requiring red cell exchange (RCE) to successfully attain and maintain low PPIX levels, but RCE was associated with hemosiderosis in 1 patient. Allogeneic stem cell transplantation (AlloSCT) was performed in 2 patients. One failed engraftment twice, whereas the second rejected the first graft but achieved full donor chimerism with a second graft and increased immunosuppression. In conclusion, our observations suggest that progressive liver disease needs parenteral PPIX-lowering treatment with the intensity adjusted to achieve a target Erc-PPIX level. Because EPP liver disease is universally recurrent, AlloSCT should be considered in all patients with adequate immunosuppression to facilitate engraftment. RCE appears to be effective for recurrent EPP liver disease but is associated with an increased risk of iron overload.

Background. The purpose of this study was to review the value of bone scans (BS) in the assessment of bone metastases from early-stage hepatocellular carcinoma (HCC) in patients assessed or waiting for liver transplant (LTx). Methods. We reviewed BS studies performed at our center for patients with early-stage HCC either being assessed for LTx, or on the waiting list for LTx, from January 2010 to May 2017. The BS findings were classified as positive, equivocal, or negative. Correlation with final outcome based on clinical and radiological follow-up was performed. Results. There were 360 BS performed in 186 patients during the study period with a mean age of 58.7 years (range, 34.9-70.4 years) and most were male patients (161/186 [86.6%]). None of the BSs resulted in delisting of patients from the LTx waiting list. Three BSs were reported as positive for metastases. All 3 were proven to be false positives on follow-up. Fourteen studies reported equivocal findings, none of which were confirmed to be metastases on follow-up. There was 1 false-negative BS: a bone metastasis was detected incidentally on magnetic resonance imaging and proven on biopsy. Conclusions. We have demonstrated that the diagnostic yield of BS in early HCC patients who are candidates for LTx is minimal, challenging the current inclusion of BS in guidelines for staging these HCC patients.

7021 Background: GA can predict the risk of toxicities of chemotherapy in older adults. Genetic risk categories correlate with OS in AML. We previously reported a reduction in early mortality in a pre-planned interim analysis of a phase II trial with the use of GA and genetic profiling to personalize therapy selection (NCT03226418) (Blood 2019; 134(s1):120). Here, we present the results of a propensity score matched analysis demonstrating an improvement in OS over a historical control. Methods: Patients ≥60 years with a new diagnosis of AML underwent GA. Patients were considered fit for intensive chemotherapy if they had robust physical function [normal activities of daily living (ADL) and instrumental ADL, and short physical performance battery score of ≥10 out of 12], normal cognitive function (Montreal Cognitive Assessment score of ≥26 out of 30), and hematopoietic cell transplantation comorbidity index (HCT CI) of 0-2 (except for treatment related AML, where a score of 0-2 in addition to the prior history of malignancy was acceptable). Genetic profiling for therapy selection relied on karyotyping and followed the 2017 ELN criteria. Fit patients with good or intermediate-risk AML received intensive chemotherapy. Patients with high-risk AML received low-intensity chemotherapy, or CPX 351 if they were fit and met the FDA-approved indications. Pragmatic aspects of the trial included broad eligibility criteria (e.g. patients on treatment for other malignancy were enrolled) and co-management of patients with community oncologists. Mortality was compared with a historical control treated during the years 2004-2016 (after approval of HMA) and matched on gender, age, Karnofsky Performance Status (KPS), HCT CI and ELN risk category. Results: Treatment group (n = 27) vs. historical controls (n = 32) were matched in terms of age (median age, 70 vs. 68.5 years), ELN risk category (adverse risk 59% vs. 53%), HCT CI (median score of 2), KPS (median 80 vs. 85), and gender (male 44% vs. 50%). In the treatment group, 3 patients received intensive chemotherapy: CPX 351 (n = 2) or 7+3+ gemtuzumab (n = 1). Other patients received HMA alone (n = 16), decitabine and midostaurin (n = 3), or azacitidine and venetoclax after the approval of venetoclax (n = 5). Treatment in the historical control included intensive chemotherapy (n = 20) such as 7+3, or mostly HMA based low intensity chemotherapy (n = 12). OS was significantly higher in the treatment group over historical control with 1-year OS of 66% (95% CI 60-87%) vs. 16% (95% CI 7-35%). Conclusions: Our model to personalize AML therapy selection represents an innovative approach to precision medicine that incorporates both GA for patient profiling and genetic profiling of leukemia cells. Our results appear promising with superior OS (an absolute difference of 50% in 1-year OS) compared to a matched historical control. Clinical trial information: NCT03226418.

Context Despite new therapies for AML, older patients with rel/ref AML do not have durable responses and are ineligible for potentially curative HCT. The SIERRA trial addresses this unmet need. Objective Midpoint analysis, with safety, engraftment data, and transplant rates. Design Phase 3, randomized patients in the CC arm who do not attain remission may then receive Iomab-B followed by HCT. Setting USA and Canada. Patients or other participants Aged ≥55 years with active rel/ref AML. Interventions Iomab-B plus RIC (FLU/TBI) and HCT, or CC. Main outcome measures Primary endpoint - durable CR (dCR) ≥ 180 days. However, this analysis is on safety and transplant rates. Results First 50% of patients (n=75) had a median age of 64, with 85% failing ≥2 induction therapies and 33% failing targeted therapies. Median baseline marrow blasts Iomab-B (30%) and CC (26%). All patients transplanted after Iomab-B engrafted (median days 15 for ANC, 18 for platelets). After randomization, 82% (31/38) patients in the CC arm failed salvage therapy, despite 32% (12/38) receiving targeted therapy. Majority (73%, 8/11) of patients receiving venetoclax with HMA or LDAC did not achieve remission. Of the 31 patients not achieving remission on CC, 20 (65%) crossed over to receive Iomab-B/HCT. The most common reason preventing crossover was disease progression. CC showed increased incidence of Grade ≥3 febrile neutropenia vs Iomab-B (46% vs 23%). Iomab-B administration was generally well tolerated with 1 Grade 3 and no Grade 4 infusion reactions. There were no Iomab-B-related deaths and 100-day non-relapse mortality was 6% on the Iomab-B arm. Conclusions Despite advanced age, active disease and many prior therapies, 84% (31/37) of all patients in the Iomab-B arm were able to undergo HCT and all successfully engrafted. In comparison, only 18% (7/38) of the patients on the CC arm achieved remission and underwent conventional HCT despite a high percentage receiving recently approved agents and targeted therapies. Iomab-B has a favorable safety profile with no graft failures and low transplant-related mortality. These preliminary results represent significant improvements over the current rates of transplantation in this patient population. SIERRA trial is currently enrolling ( www.sierratrial.com or clinicaltrials.gov NCT02665065 ).

e19129 Background: Increasing age is associated with greater comorbidity burden. We hypothesized that comorbidity burden predicts 1-month mortality and OS in patients (pts) aged ≥60 y with AML. Methods: We utilized the National Cancer Data Base to identify pts aged≥60 y with AML diagnosed between 2004-2014. Pts were divided into 3 groups with CCI scores of 0, 1 and ≥2. Chi-square tests were used to examine the association between CCI and different variables. Logistic regression and cox proportional hazard models were used to determine predictors of 1-month mortality and OS, respectively. Results: Of 50,668 pts, 65% had CCI of 0, 24% CCI of 1 and 11% CCI of ≥2. 34% did not receive chemotherapy. 4% underwent upfront hematopoietic cell transplant (HCT). Pts with CCI of 0 were more likely to receive chemotherapy, especially multiagent chemotherapy (42% vs 39% vs 28%) and undergo HCT (4% vs 3% vs 1%). 1-month mortality was 24%, 34% and 45% for pts with CCI of 0, 1 and ≥2, respectively. In a multivariable analysis, 1-month mortality was worse with CCI of 1 (OR 1.5, 95% CI 1.4-1.6) or CCI of ≥2 (OR 2.3, 95% CI 2.2-2.5) vs CCI of 0. Lower CCI, younger age, male sex, white race, higher annual income, private insurance, multiagent chemotherapy, receipt of HCT, acute promyelocytic leukemia (APL) and diagnosis after 2009 were associated with improved OS (Table). Conclusions: In one of the largest real-world studies, we demonstrated that 1/3rd of newly diagnosed AML did not receive chemotherapy. Greater comorbidity, measured by higher CCI, was more common with increasing age, and correlated with lower likelihood of receiving chemotherapy. Higher CCI independently predicted worse early mortality and OS in older pts with AML. Trials are warranted to determine the effect of optimized comorbidity management and supportive care to reduce early mortality and improve OS. [Table: see text]

INTRODUCTION: Hepatic steatosis is a common incidental finding on computed tomography (CT) in patients presenting to the emergency department (ED). The aims of our study were to assess the prevalence of hepatic steatosis in ED patients with suspected renal colic and to assess documentation in radiology reports and medical charts correlated with alanine transaminase (ALT) levels. METHODS: Over 18 months from January 2016 to June 2017, all unenhanced CTs performed for suspected renal colic were reviewed. Quantitative assessment measuring hepatic and splenic attenuation in Hounsfield Units was performed. Hepatic steatosis was defined using multiple CT criteria including liver/spleen (L/S) ratio. Radiology reports, medical charts and ALT levels, if collected within 24 h of CT, were reviewed. RESULTS: A total of 1290 patients were included with a median age 52.5 years (range 16-98) and male predominance (835 [64.7%]). A total of 336 (26%) patients had hepatic steatosis measured by L/S ratio of ≤ 1.0. Ninety-four patients (28%) had radiology reports noting steatosis. Documentation in medical charts was noted in 18 of the 94 patients (19.1%) for whom steatosis was reported. Liver enzymes were available for 704 (54.6%) patients. There was a significantly higher mean ALT level in patients with hepatic steatosis (42.2 U/L; 95% CI 38.4-46.0) compared to patients without (28.8 U/L; 95% CI 25.7-31.9) (P

Gastroenterology 2016;150:1542–1544 A 53-year-old safety inspector from rural Australia was transferred to a major liver center with liver failure, one week after presentation to another hospital with 10 days of fevers, headache, lethargy and myalgias and a chest x-ray showing right basal consolidative changes. He was treated initially for communityacquired pneumonia with ceftriaxone. Despite an improvement in his respiratory status, his clinic state deteriorated with ongoing fevers and worsening hyperbilirubinemia, coagulopathy and renal impairment requiring hospital transfer and admission to the high dependency unit where his antibiotics were changed to tazobactam and piperacillin. His past history included type 2 diabetes mellitus, hypertension and a chronic alcohol intake of over 400 grams per week. He had no history of recent travel and no close contacts were unwell. His medications were atenolol, amlodipine and valsartan. He was an ex-smoker. He had recently worked in an abattoir (a slaughterhouse) inspecting conditions for the processing of cattle. Blood tests at the time showed a normocytic anaemia with haemoglobin of 98g/L (reference range 130-180g/L), white cell count 12.3x10/L (4.0-11.0x10), neutrophils 10.1x10/L (2-7.5x10), lymphocytes 0.5x10/L (1.0-4.0x10), international normalized ratio 2.2, urea 12.2 mmol/L (3.0-9.2mmol/L), creatinine 114 micromol/L (62 micromol/L to 106 micromol/L), bilirubin 337 micromol/L ( 3200 units). CT of the abdomen showed features consistent with underlying cirrhosis with portal hypertension and small volume ascites, but no lymphadenopathy or mass lesions were seen. He was treated for presumed alcoholic hepatitis with pentoxyfilline for 1 week with no improvement in his clinical state and persistent liver function derangement, with bilrubin rising to 324 micromol/L, ALT 113 units/L and AST 133units/L. A liver biopsy was performed which showed background cirrhosis with a steatohepatitis pattern as well as extensive small granulomas (Figure A) with the appearance of poorly formed rings surrounding a central lipid vacuole (Figure B).