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Introduction: Cognitive computing point-of-care decision support tools which ingest patient attributes from electronic health records and display treatment options based on expert training and medical literature, supplemented by real world evidence (RWE), might prove useful to expert and novice oncologists. The concordance of augmented intelligence systems with best medical practices and potential influences on physician behavior remain unknown., Methods: Electronic health records from 88 breast cancer patients evaluated at a USA tertiary care center were presented to subspecialist experts and oncologists focusing on other disease states with and without reviewing the IBM Watson for Oncology with Cota RWE platform., Results: The cognitive computing "recommended" option was concordant with selection by breast cancer experts in 78.5% and "for consideration" option was selected in 9.4%, yielding agreements in 87.9%. Fifty-nine percent of non-concordant responses were generated from 8% of cases. In the Cota observational database 69.3% of matched controls were treated with "recommended," 11.4% "for consideration", and 19.3% "not recommended." Without guidance from Watson for Oncology (WfO)/Cota RWE, novice oncologists chose 75.5% recommended/for consideration treatments which improved to 95.3% with WfO/Cota RWE. The novices were more likely than experts to choose a non-recommended option (P < .01) without WfO/Cota RWE and changed decisions in 39% cases., Conclusions: Watson for Oncology with Cota RWE options were largely concordant with disease expert judged best oncology practices, and was able to improve treatment decisions among breast cancer novices. The observation that nearly a fifth of patients with similar disease characteristics received non-recommended options in a real world database highlights a need for decision support., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives: Value-based payment reforms shift cost-containment responsibilities to the physician. Although gene expression profiling (GEP) utilizing a 21-gene panel among patients with early-stage, axillary lymph node-negative, hormone receptor-positive, HER2/neu oncogene-negative breast cancer is able to identify a cohort that may achieve excellent outcomes without adjuvant chemotherapy, high up-front costs (list price, $4175) could dissuade usage., Study Design: Retrospective review of consecutive patients with breast cancer treated at a single cancer center., Methods: Chart review of 227 patients 70 years or younger with outpatient costs (ie, drug average sales price, reagent costs, physician charges) during first 6 months of treatment., Results: Of these patients, 68% underwent GEP, with 52%, 43%, and 5% having low, intermediate, and high recurrence risk scores, respectively. Adjuvant chemotherapy was utilized less in genomically profiled cohorts (19% vs 29%; P = .08) and was consistent with recommendations of the recurrence scores. The mean 6-month outpatient costs were $24,955 with adjuvant chemotherapy and $2654 with hormonal therapy. Patients with stage II cancer undergoing GEP received adjuvant chemotherapy at a lower frequency (28.6% vs 86.7%), but patients with stage I cancer who underwent testing were slightly more likely to receive chemotherapy (15.8% vs 14%) because the test identified patients with higher-risk tumors. Universal GEP testing of patients with stage II cancer would have resulted in net savings of $11,494 per patient inclusive of test cost; stage I testing would have increased costs by $4505. Similar trends for grade 2/3 tumors (-$2394) and grade 1 tumors (+$6047) were noted., Conclusions: Universal GEP testing of women 70 years or younger with stage II or grade 2/3 lymph node-negative breast cancers would result in lower outpatient costs, inclusive of the diagnostic test, within the first 6-month episode of care.

Efforts to reduce relapse of non-Hodgkin lymphoma after autologous transplantation have included ex vivo stem cell selection and/or peritransplantation immunotherapy. The late infectious and immunologic consequences of these maneuvers are not well understood, although an increase in early cytomegaloviral disease after CD34(+) stem cell selection and an alteration in immunoglobulin and T-cell recovery after peritransplantation rituximab has been noted. We report the first 2 cases of progressive multifocal leukoencephalopathy caused by JC papovavirus after autologous peripheral blood stem cell transplantation and a case each of cytomegalovirus retinitis and pneumonitis. All 4 patients experienced significant impairment of CD4 T-cell recovery, placing them at risk for these unusual viral infections. The clustering of cases is concerning because all occurred shortly after the introduction of peritransplantation rituximab into treatment protocols (4 of 62 immunotherapy recipients compared with 0 of 276 without; z = 3.595; P <.001), although a direct association with this CD20 B-cell-directed therapy remains speculative.

Presented here are 16 case studies of adults with immune (idiopathic) thrombocytopenic purpura (ITP); 5 were treated at Hackensack University Medical Center (HUMC), Hackensack, NJ, and 11 were treated at the Allegheny University Hospital (AUH), Medical College of Pennsylvania. Four of the 5 patients at HUMC had initial transient responses to intravenous immunoglobulin G (IVIg) therapy and required large doses of corticosteroids to maintain platelet counts over 50,000 microL. One elderly patient with systemic lupus erythematosus (SLE) had been treated unsuccessfully with corticosteroids and immunosuppressants to maintain her platelet count over 50,000 microL. All 5 patients were given 1 or 2 doses of anti-D at 50 microg/kg, leading to complete resolution of ITP. Following anti-D therapy, patients were tapered off corticosteroids and currently remain in complete remission with platelet counts over 100,000/ microL. The mechanism of action of anti-D in ITP remains unclear and requires further study. Treatment of the 11 patients at AUH began with corticosteroids, which resulted in no durable therapeutic response. Anti-D was then given at 50 microg/kg, and this provoked an excellent response with a prompt recovery of platelet levels to 100,000/ microL, after which active treatment was halted. Patients were monitored by direct office visit every 3 months unless a clinical indication required an earlier return. If the patient's platelets dropped below 100,000/ microL, they were first given prednisone. As of the last follow-up, all 11 patients remain stable and no patients have required splenectomy.

Since a vitamin K dependent protein, protein C, can inactivate factor VIII, a study was undertaken to determine if the level and stability of factor VIII in plasma are influenced by such a protein. Factor VIII lability was determined by incubating citrated plasma, diluted 1:10 and 1:20 in pH 7 X 2 imidizole buffer, for 6 h at 37 degrees C. Normal plasma had a mean factor VIII of 98 +/- 61 U/100 ml. The amount of factor VIII remaining after 6 h of incubation was 68 +/- 14% of the original factor VIII level. In warfarinized patients, factor VIII (218 +/- 65 U/100 ml) and VWF:AGN (331 +/- 102 U/100 ml) were elevated (P less than 0.001). Following incubation, their residual activity was 103 +/- 20% of the original factor VIII level. In samples taken after warfarin was discontinued, normal factor VIII lability returned, while plasma levels of factor VIII and VWF:AGN remained elevated. Similarly, in the plasma of a vitamin K deficient patient, increased factor VIII stability was also evident; lability was restored following vitamin K replacement. We conclude that factor VIII stability is determined in part by a vitamin K dependent protein. In clinical states in which this protein is functionally absent, factor VIII is elevated and more stable.

Philadelphia (Ph) chromosome negative chronic myeloid leukemia (CML) can be distinguished from clinically similar disorders on the basis of the presence of rearrangement of the breakpoint cluster region (bcr) of chromosome 22. We have identified six patients with Ph-negative CML, each with bcr rearrangement. Apparently normal karyotypes were observed in two cases, and a third contained a rearrangement that did not appear to involve chromosomes 9 or 22. The other three cases had translocations involving chromosome band 9q34 but no case contained the common derivative chromosome 9pter----9q34::22q11----22qter. One case appeared to contain either a deletion of an unrearranged bcr locus in approximately 50% of cells or duplication of rearranged bcr, both 5' and 3' of the chromosome 22 breakpoint. Considerable complexity exists in the types of genetic changes that can juxtapose bcr and the c-abl oncogene in CML. Based on the molecular and cytogenetic analyses of these and other cases described in the literature, we conclude that most cases of true Ph-negative CML arise from submicroscopic genetic exchanges rather than masking of simple t(9;22)(q34;q11) translocations by secondary rearrangements.