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INTRODUCTION: Dehydrated hereditary stomatocytosis (DHSt) is an autosomal dominant red blood cell membrane disorder characterized by hemolytic anemia and splenomegaly. DHSt has an estimated incidence of 1:50,000 births, and the degree of anemia varies within and between families. Although transfusion support during childhood is not uncommon, continued requirement into adulthood is rare. The most frequent cause of DHSt is a gain-of-function mutation of the PIEZO1 gene, leading to delayed channel inactivation that results in a monovalent cation leak and an increase in intracellular calcium (Ca2+). Many of these patients develop recurrent thromboses post splenectomy. Other DHSt patients have mutations in KCNN4, which encodes the Gardos channel, with mutations causing increased Ca2+ sensitivity and potassium efflux. To our knowledge, 42 patients from ten families have been described with four distinct KCNN4 mutations: Arg352His, Val282Met or Val282Glu, and a 28bp deletion encompassing the exon-intron 7 junction. We report herein the eighth family with the Arg352His locus mutation. CASE REPORT: Five subjects from a single family were enrolled in this study (affected proband, unaffected husband, two affected children, and an unaffected grandchild). The proband has had hemolytic anemia since childhood. She had undergone splenectomy at age three and cholecystectomy at eight. Her anemia persisted, with a mean hemoglobin (Hgb) of 10.5g/dL and a reticulocyte count (retic ct) of 12.6%, with no need for transfusion support or iron chelation therapy (Table 1). Extensive testing revealed slightly decreased osmotic fragility and mildly elevated intracellular sodium concentration, of 19.4 mEq/L. Her daughter has mild splenomegaly and anemia, with a mean Hgb of 11.1g/dL and retic ct of 6.7%, whereas her son has more severe disease, with a mean Hgb of 9.3g/dL and a retic ct of >22%. He underwent splenectomy as a teenager for immune thrombocytopenia, and has required chelation therapy with deferasirox since age 31, when his ferritin rose to >1000ng/mL. Similar to results reported by others, splenectomy did not alter the severity of hemolysis in either the proband or her son, and neither developed thrombotic complications 57 and 7 years post splenectomy, respectively. The proband's daughter has a child with a normal Hgb, and is presumed unaffected. Stomatocytes were rarely seen on the peripheral blood smears of the proband and her children. METHODS: A clinically available 39 gene hemolytic anemia panel on the proband failed to identify the mutation underlying this disorder. We therefore performed whole exome sequencing on all five family members. We prioritized the analysis of 23 additional genes that are included in hemolytic anemia panels from two other reference laboratories and are involved in disorders of red blood cell membrane or cytoskeletal proteins of potential clinical relevance to the study population. RESULTS: A single missense mutation, Arg352His within KCNN4, was identified in all three affected individuals. This heterozygous mutation was present in the proband and her affected two children, and absent in her unaffected grandchild and husband. CONCLUSIONS: To our knowledge, this Pennsylvania family is only the eleventh described to have DHSt secondary to a KCNN4 mutation. This disorder is likely much more prevalent than reported, due to the rarity of stomatocytes on peripheral blood smears, the omission of the KCNN4 gene from hemolytic panels offered by some reference laboratories, and variable clinical presentation. KCNN4 mutations should be investigated if other causes are not identified in patients with lifelong hemolytic anemia suspected of having a red cell membrane protein or cytoskeletal disorder. Appropriate diagnosis may allow severely affected patients to be considered for treatment with the experimental Gardos channel inhibitor senicapoc. Additionally, mutational diagnosis is especially important when considering the adverse outcomes post splenectomy in PIEZO1 as compared to KCNN4 mutations. Disclosures Eyster: SPARK:Research Funding;Sanofi:Research Funding;Novo Nordisk:Research Funding;Baxalta/Shire:Research Funding.

46 Background: Research has demonstrated that early palliative care involvement for patients with advanced cancer has multiple benefits, including improved symptom control/quality of life and reduced readmission rates. Based on this data, the American Society of Clinical Oncology (ASCO) has developed guidelines for early palliative care consultation. At the University of Vermont Medical Center, historically 40% of such patients were evaluated by palliative care during hospital admission. The purpose of this study was to better integrate palliative care into the oncology inpatient setting through the use of a standardized admission template. Methods: A specific oncology H&P template, with inclusion of a drop down menu of ASCO based criteria for palliative care consultation, was created. Providers were educated on template use, and data then were collected for oncology admissions from 2/1-8/31/2018 regarding template usage, if criteria was met for palliative care consultation, and whether consultation occurred. Additionally, 30 day post discharge ED visits and readmissions were recorded, extending data collection for this purpose to 9/30/2018. Results: There were 372 medical oncology admissions during the studied time period, with 284 individual patients. The template was used for 95 (26%) admissions. 267 of those patients admitted qualified for palliative care consultation and, of those in which the template was used, 72% had palliative care consulted versus 50% without the template (p= 0.0013). There was no statistically significant difference in readmission rates between those with palliative care consultation and without. Conclusions: Early palliative care consultation for patients with advanced malignancy has been shown to have multiple benefits on an individual and system-wide basis. It was shown in this study that, though the created template was used for a minority of admissions, with template use a significantly greater proportion of appropriate patients had palliative care consulted. This suggests that, with more widespread practice, this strategy could further promote inpatient palliative care involvement for appropriate oncology patients.

Colorectal cancer is one of the most common malignant diseases in the United States and worldwide, and it remains among the top three causes of cancer-related death. A new understanding of molecular characteristics has changed the profile of colorectal cancer and its treatment. Even controlling for known mutational differences, tumor side of origin has emerged as an independent prognostic factor, and one that impacts response to therapy. Left- and right-sided colon cancers differ in a number of key ways, including histology, mutational profile, carcinogenesis pathways, and microbiomes. Moreover, the frequency of certain molecular features gradually changes from the ascending colon to rectum. These, as well as features yet to be identified, are likely responsible for the ongoing role of tumor sidedness and colorectal subsites in treatment response and prognosis. Along with tumor molecular profiling, blood-based biopsy enables the identification of targetable mutations and predictive biomarkers of treatment response. With the application of known tumor characteristics including sidedness and subsites as well as the utilization of blood-based biopsy, along with the development of biomarkers and targeted therapies, the field of colorectal cancer continues to evolve towards the personalized management of a heterogeneous cancer.