Citations

321 Background: G3 NENs are aggressive, and optimal systemic treatment is unclear. Temozolomide (TEM)-based regimens have been used to treat grade 1-2 NETs, but their efficacy in G3 NENs (Ki-67 > 20%) remains undetermined. Aims: To assess the clinical efficacy of TEM-containing regimens in advanced grade III gastroenteropancreatic NENs (GEPNENs). Methods: A multicentre retrospective review (2008-2017) of patients with metastatic/unresectable G3 GEPNENs who received a TEM-containing regimen. The primary endpoint was time to treatment failure (TTF). Radiologic response was extracted from local reports without formal RECIST criteria. Results: 118 patients in six centers were included (median age 55, 65% male, 15% functional, 75% pancreatic NEN). 57% were well-differentiated, 35% poorly-differentiated, and 18% unknown based on local pathology reports. The regimen used was CAPTEM in 93% and TEM in 7%. Best radiological responses were: complete response (1%), partial response (39%), stable disease (22%), progressive disease (31%), unknown (7%) not by RECIST. Median TTF was 150 days and median overall survival (OS) 18.0 months. Fifteen patients (14%) required dose reductions/discontinuation due to adverse events. TTF was shorter for patients on TEM alone (p = 0.02, Table 1). Well-differentiated NENs had better response rate (52% vs 26%, p = 0.02) and overall survival (30.1 vs 12.0 mo, p = 0.008) compared to poorly-differentiated NEN. Conclusions: This is the largest TEM treatment series in G3 NEN, involving collaboration of several major North American NET centers. 40% of patients showed some degree of response, and treatment was generally well-tolerated. TEM-based regimens should be considered a viable treatment option in this setting. Prospective confirmatory trials (such as EA2142) may face difficulties in accrual due to disease rarity. [Table: see text]

BackgroundClinician preferences and practices regarding appropriate vasopressin use in light of its increased acquisition cost secondary to rebranding has not been evaluated or described since the most recent iteration of the Surviving Sepsis Campaign Guideline was published.ObjectiveTo assess vasopressin cost containment initiatives and pharmacists' opinions regarding appropriate vasopressin use.MethodsA scenario‐based survey was distributed to critical care and emergency medicine pharmacists. Responses were characterized using frequency and descriptive statistics. Categorical variables between those who implemented changes (Vasopressin Cost Consideration) and those who did not (Usual Care) were compared using chi‐square or Fisher's exact tests. McNemar's test was used to compare responses in clinical scenarios between Vasopressin Cost Consideration and Usual Care groups.ResultsAmong 1757 pharmacists surveyed, 200 (11.3%) responded. When respondents considered vasopressin cost and evidence (vs evidence alone), fewer respondents would use vasopressin adjunctively with norepinephrine (21% vs 26.6%, P = 0.031), to raise mean arterial pressure compared with epinephrine (65.2% vs 72.3%, P = 0.012), or to reduce norepinephrine infusion rates (71.4% vs 81.4%, P < 0.001), but would use with steroids (62.4% vs 28.3%, P < 0.001). Most (72%) respondents had implemented vasopressin cost containment and/or education initiatives. The Vasopressin Cost Consideration group respondents were more likely to initiate vasopressin at 0.03 units/minute without titrating (47.9% vs 33.9%, P = 0.045).ConclusionSince vasopressin was generically rebranded, most institutions have implemented at least one initiative to reduce vasopressin use and/or educate clinicians about its appropriate use. When vasopressin acquisition costs were considered, pharmacists recommended its use less frequently, particularly in clinical scenarios where its use is controversial.

AbstractAs more biomarkers for Alzheimer’s disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.

ABSTRACT Background and purpose: The use of pulmonary ultrasound (US) in the critical care setting has been increasing over the past 2 decades. The use of advanced practice providers (APPs) in the critical care setting is also increasing. Limited data exist regarding the clinical and educational impact of a formal pulmonary US training course for APPs working in critical care settings. Methods: A preimplementation and postimplementation comparative design focused on the development and implementation of a formal pulmonary US course for novice critical care APPs. Conclusions: Eleven APPs underwent formal pulmonary US training. There was a significant increase in pulmonary US knowledge after the course, with pretest median of 13 and posttest median of 22 (p < .001; maximum score = 23). Presurvey and postsurvey comparison showed overall increase in skill and clinical use of pulmonary US. After the course, participating APPs reported a greater frequency of clinical decision-making based on US examination as measured by presurvey and postsurvey results. Implications for practice: Implementation of a formal pulmonary US course for critical care APPs improved pulmonary US knowledge, skill, and utilization, and impacted clinical decision-making and should be a highly recommended addition to the practice setting.

TPS873 Background: Initial treatment of metastatic colorectal cancer (mCRC) involves a 5-fluorouracil based chemotherapy regimen, often in combination with anti-VEGF therapy. Upon disease progression, multiple studies have suggested a benefit for continued anti-VEGF therapy. There is increasing evidence that VEGF plays a role in cancer immune evasion. Targeting of inflammatory and immune checkpoints are attractive approaches to enhance the benefits of anti-VEGF therapy. The safety and activity of the anti-PD-L1 antibody atezolizumab with bevacizumab and with 5-FU, oxaliplatin, and bevacizumab have been recently reported; the combinations were well-tolerated and suggested clinical activity. Therefore, bevacizumab may increase the immunogenicity of colorectal cancers, and the combination of atezolizumab plus bevacizumab may be associated with clinically meaningful response rates and disease control. Furthermore, there may be candidate biomarkers that may identify those patients most likely to benefit from this combination. Methods: In this randomized, double-blind, multicenter, placebo-controlled phase II study, 135 patients with mCRC will be randomized 2:1 to receive capecitabine/bevacizumab/atezolizumab or capecitabine/bevacizumab/placebo. Patients with prior PD-L1/PD-1 therapy are ineligible. Primary and secondary efficacy will be conducted using ITT analysis. Safety analyses will include all randomized patients who receive at least one dose of study treatment. The primary objective is PFS. The secondary objectives are ORR, OS, safety, and tolerability. The primary comparison will be superiority of the active treatment for the PFS endpoint, atezolizumab versus placebo testing at 1-sided α = 0.1 (log rank test). A PFS hazard ratio of 0.618 (active treatment versus placebo) is detectable with 86% power (1 sided α = 0.1). No interim analyses for futility or efficacy will be conducted. A subset analysis will be performed in the microsatellite-high patients looking at potential differences in PFS and OS. Trial is active and currently recruiting patients. Clinical trial information: NCT02873195.

Currarino triad is a rare hereditary condition characterized by anorectal malformation, sacral dysgenesis, and a presacral mass. Neuraxial anesthetic techniques pose increased risks to patients with spinal malformations. Ultrasound imaging improves accuracy of intervertebral level identification compared to clinical estimation. We present the case of a parturient with Currarino triad and a low conus medullaris undergoing cesarean delivery where preprocedural magnetic resonance imaging and ultrasound imaging allowed for successful combined spinal-epidural anesthesia to be performed. Despite these measures, however, the patient did develop a high spinal and temporary postoperative dizziness.