Citations

Study ObjectiveHigh‐dose intravenous vitamin C is a potential treatment option for patients with sepsis and may interfere with point‐of‐care (POC) blood glucose (BG) testing. This study aimed to determine if vitamin C dosing used for sepsis affected POC BG level results.DesignProspective observational pilot study.SettingIntensive care unit in a large academic tertiary care medical center.PatientsFive consecutive critically ill adults hospitalized between April 1 and June 1, 2017, who received two or more doses of intravenous vitamin C 1500 mg for the treatment of sepsis and had at least two paired POC BG levels and laboratory venous BG levels measured within 1 hour of each other during vitamin C therapy.Measurements and Main ResultsThe performance of POC BG level measurement was compared with the reference method of laboratory BG level measurement. The concordance to minimum accuracy criteria for BG meters set forth by the International Organization for Standardization (ISO) 15197:2013, the measurement of agreement between POC BG level and laboratory BG level using the Bland‐Altman method, and the clinical accuracy through Parkes error grid analysis were assessed. A total of 16 paired POC and laboratory BG level measurements from the five patients were included. The accuracy of POC BG with laboratory BG level measurements during vitamin C administration according to ISO 15197:2013 criteria was 81.3%, which did not meet the minimum accuracy criteria of 95%. The Bland‐Altman analysis showed a mean difference between POC and laboratory BG levels of 8.9 mg/dl, and the Parkes error grid analysis showed that the differences between POC and laboratory BG level measurements would not have resulted in a change in clinical action.ConclusionThe accuracy and agreement of POC and laboratory BG level measurements in critically ill patients receiving vitamin C were consistent with previously published reports in critically ill patients not receiving vitamin C and did not demonstrate clinically significant interference due to vitamin C dosing for sepsis.

e15626 Background: FGFR2 fusions are found in 10-15% of intrahepatic cholangiocarcinomas. Individuals with FGFR2 fusions have a better prognosis and more indolent natural history. More recently FGFR2 fusions have been described as a predictive marker for tyrosine kinase inhibitors targeting the FGFR2 pathway. Texture analysis from CT imaging has been used in the past to estimate degree of fibrosis and angiogenesis in various tumors types; however, texture analysis has not been used in the past to detect FGFR2 rearrangements. Methods: This is a retrospective study of 33 patients with intrahepatic cholangiocarcinoma who were previously tested for FGFR2 fusions with either a FISH break apart assay or with clinically available next generation sequencing assays. All patients had a contrast enhanced CT performed. To address physiological and pathological variations, matched-size regions of interest (ROIs) over areas of non-necrotic tumor and unaffected liver during the portal venous phase were drawn. The paired ROIs for each patient were then processed via an imaging analytic pipeline for (1) ROI normalization, (2) texture panel creation, and (3) machine learning predictive model development. Results: Fifteen patients with FGFR2 fusions and 18 patients without FGFR2 fusions were included in the study. Using the developed predictive model, accurate FGFR2 fusion classification in 90% of cases was achieved (sensitivity = 87%, specificity = 94%). Conclusions: Utilizing advanced analytics with machine learning techniques, multi-textural data obtained from conventional CT images has the capability to detect genetic aberrations in intrahepatic cholangiocarcinoma, including FGFR2 gene fusions. Radiogenomic evaluation has several attractive benefits including the cost effective and expeditious detection of actionable mutations such as FGFR2 fusions as well as avoidance of invasive procedures such as percutaneous core biopsies. [Table: see text]

TPS4142 Background: Advanced cholangiocarcinoma (CC) is a life-threatening disease for which there are limited therapeutic options. Mutations in isocitrate dehydrogenase 1 (mIDH1) occur in up to 25% of intrahepatic CC cases. mIDH1 lead to epigenetic and genetic changes that promote oncogenesis via production of the oncometabolite, D-2-hydroxyglutarate (2-HG). AG-120 is a first-in-class oral inhibitor of the mIDH1 enzyme, and is being tested in a phase 1 study that enrolled 73 patients (pts) with mIDH1 CC who had received a median of 2 prior therapies (range 1–5). AG-120 has demonstrated a favorable safety profile and clinical activity in this study. Among the 72 efficacy evaluable pts (≥1 post-baseline response assessment or discontinued prematurely), 6% (n = 4) had a confirmed partial response and 56% (n = 40) had stable disease. Progression-free survival (PFS) rate at 6 months was 40% as of Dec 16, 2016. The 500 mg once daily (QD) dose of AG-120 was selected for the ongoing phase 3 study in mIDH1 CC described here. Methods: ClarIDHy is a global, phase 3, multicenter, double-blind study randomizing 186 pts with mIDH1 CC in a 2:1 ratio to AG-120 (500 mg QD) or matched placebo (NCT02989857). Key eligibility criteria: nonresectable or metastatic CC; documented mIDH1 based on central laboratory testing; ECOG 0–1; measurable disease (RECIST v1.1); documented disease progression following ≤2 prior systemic therapies in the advanced setting, including at least 1 gemcitabine- or 5-fluorouracil-containing regimen; and no prior mIDH inhibitor therapy. Crossover from the placebo arm to the AG-120 arm will be permitted. The primary endpoint is PFS as assessed by an independent review. Secondary endpoints include safety, tolerability, overall response rate, overall survival, pharmacokinetic and pharmacodynamic analyses on plasma, and quality of life as assessed by the EORTC QLQ-C30, EORTC QLQ-BIL21, and EQ-5D-5L instruments. An independent data monitoring committee will monitor the data throughout the study. The ClarIDHy study is currently activated at participating sites in the US and will be activated in centers throughout Europe and in South Korea. Clinical trial information: NCT02989857.

Background and ObjectivesA high proportion of persons in institutionalized settings such as the criminal justice system and psychiatric hospitals have substance use disorders (SUDs). We explored the association between substance use, demographics, and criminal justice involvement in a population of patients placed on involuntary 72‐h holds in a psychiatric facility.MethodsWe retrospectively identified patients aged 18 through 57 years who had been placed on 72‐h holds during an acute psychiatric hospitalization during a 1‐year period. Data were analyzed with standard descriptive statistics, and data collection was reviewed by 2 randomly assigned psychiatrists.ResultsWe identified 336 patients placed on 72‐h holds during an acute psychiatric stay. Of these, more than two‐thirds (68.5%; n = 230) had an SUD. Compared with patients not using substances, those with SUDs were significantly more likely to be younger (p = .003), male (p = .005), and unmarried (p < .001) and to have criminal justice involvement before (p < .001) and after hospitalization (p < .001). The rate of unemployment was similarly high in both users (67.4%) and nonusers (69.2%).Discussion and ConclusionsMost patients on involuntary psychiatric holds have comorbid SUDs. These patients are more likely to have interacted with the criminal justice system and less likely to have social support in the form of marriage. Unemployment was common among all patients.Scientific SignificanceWhen SUDs are not treated by the criminal justice or mental health system, rehospitalization and criminal recidivism may result. (Am J Addict 2018;27:574–577)

Focused cardiac ultrasonography is performed by clinicians at the bedside and is used in time‐sensitive scenarios to evaluate a patient's cardiovascular status when comprehensive echocardiography is not immediately available. This simplified cardiac ultrasonography is often performed by noncardiologists using small, portable devices to augment the physical examination, triage patients, and direct management in both critical care and outpatient settings. However, as the use of focused cardiac ultrasonography continues to expand, careful consideration is required regarding training, scope of practice, impact on patient outcomes, and medicolegal implications. In this review, we examine some of the challenges with rapid uptake of this technique and explore the benefits and potential risk of focused cardiac ultrasonography. We propose possible mechanisms for cross‐specialty collaboration, quality improvement, and oversight.