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Abstract Background Intrathecal opioids are routinely administered during spinal anesthesia for postcesarean analgesia. The effectiveness of intrathecal morphine for postcesarean analgesia is well established, and the use of intrathecal hydromorphone is growing. No prospective studies have compared the effectiveness of equipotent doses of intrathecal morphine versus intrathecal hydromorphone as part of a multimodal analgesic regimen for postcesarean analgesia. The authors hypothesized that intrathecal morphine would result in superior analgesia compared with intrathecal hydromorphone 24 h after delivery. Methods In this single-center, double-blinded, randomized trial, 138 parturients undergoing scheduled cesarean delivery were randomized to receive 150 µg of intrathecal morphine or 75 µg of intrathecal hydromorphone as part of a primary spinal anesthetic and multimodal analgesic regimen; 134 parturients were included in the analysis. The primary outcome was the numerical rating scale score for pain with movement 24 h after delivery. Static and dynamic pain scores, nausea, pruritus, degree of sedation, and patient satisfaction were assessed every 6 h for 36 h postpartum. Total opioid consumption was recorded. Results There was no significant difference in pain scores with movement at 24 h (intrathecal hydromorphone median [25th, 75th] 4 [3, 5] and intrathecal morphine 3 [2, 4.5]) or at any time point (estimated difference, 0.5; 95% CI, 0 to 1; P = 0.139). Opioid received in the first 24 h did not differ between groups (median [25th, 75th] oral morphine milligram equivalents for intrathecal hydromorphone 30 [7.5, 45.06] vs. intrathecal morphine 22.5 [14.0, 37.5], P = 0.769). From Kaplan–Meier analysis, the median time to first opioid request was 5.4 h for hydromorphone and 12.1 h for morphine (log-rank test P = 0.200). Conclusions Although the hypothesis was that intrathecal morphine would provide superior analgesia to intrathecal hydromorphone, the results did not confirm this. At the doses studied, both intrathecal morphine and intrathecal hydromorphone provide effective postcesarean analgesia when combined with a multimodal analgesia regimen. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Abstract Aims The aim of this study is to evaluate the contemporary use of a pulmonary artery catheter (PAC) in acute myocardial infarction-cardiogenic shock (AMI-CS). Methods and results A retrospective cohort of AMI-CS admissions using the National Inpatient Sample (2000–2014) was identified. Admissions with concomitant cardiac surgery or non-AMI aetiology for cardiogenic shock were excluded. The outcomes of interest were in-hospital mortality, resource utilization, and temporal trends in cohorts with and without PAC use. In the non-PAC cohort, the use and outcomes of right heart catheterization was evaluated. Multivariable regression and propensity matching was used to adjust for confounding. During 2000–2014, 364 001 admissions with AMI-CS were included. PAC was used in 8.1% with a 75% decrease during over the study period (13.9% to 5.4%). Greater proportion of admissions to urban teaching hospitals received PACs (9.5%) compared with urban non-teaching (7.1%) and rural hospitals (5.4%); P < 0.001. Younger age, male sex, white race, higher comorbidity, noncardiac organ failure, use of mechanical circulatory support, and noncardiac support were independent predictors of PAC use. The PAC cohort had higher in-hospital mortality (adjusted odds ratio 1.07 [95% confidence interval 1.04–1.10]), longer length of stay (10.9 ± 10.9 vs. 8.2 ± 9.3 days), higher hospitalization costs ($128 247 ± 138 181 vs. $96 509 ± 116 060), and lesser discharges to home (36.3% vs. 46.4%) (all P < 0.001). In 6200 propensity-matched pairs, in-hospital mortality was comparable between the two cohorts (odds ratio 1.01 [95% confidence interval 0.94–1.08]). Right heart catheterization was used in 12.5% of non-PAC admissions and was a marker of greater severity but did not indicate worse outcomes. Conclusions In AMI-CS, there was a 75% decrease in PAC use between 2000 and 2014. Admissions receiving a PAC were a higher risk cohort with worse clinical outcomes.

Summary Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37–144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. Out of the 1 752 patients who achieved CR, 11·7% underwent autologous and 40·6% allogeneic transplant, while in CR1. Of the autologous patients, 43·2% relapsed early and 3·4% relapsed late. However, among the allogeneic patients, 13·2% relapsed early and only 1·3% late. The five‐year overall survival from relapse was 5·8% and 20% in the early and late relapse patients respectively. In conclusion, late relapse in adults with ALL is not uncommon, and is associated with better outcome after relapse compared to early relapse.

Abstract The importance of fetal placental macrophages (Hofbauer cell [HCs]) is underscored by their appearance 18 d postconception and maintenance through term; however, how human HCs evolve during healthy pregnancy and how microenvironment and ontogeny impact phenotype and function remain unknown. In this study, we comprehensively classify human HCs ex vivo, interrogate phenotypic plasticity, and characterize antiviral immune responses through gestation. Activated HCs were abundant in early pregnancy and decreased by term; molecular signatures emphasize inflammatory phenotypes early in gestation. Frequency of HCs with regulatory phenotypes remained high through term. Furthermore, term HCs exhibited blunted responses to stimulation, indicating reduced plasticity. IFN-λ1 is a key placental IFN that appeared less protective than IFN-α, suggesting a potential weakness in antiviral immunity. Ligand-specific responses were temporally regulated: we noted an absence of inflammatory mediators and reduced antiviral gene transcription following RIG-I activation at term despite all HCs producing inflammatory mediators following IFN-γ plus LPS stimulation. Collectively, we demonstrate sequential, evolving immunity as part of the natural history of HCs through gestation.

AbstractBackgroundPatients with concomitant cardiac arrest (CA) and shock are at increased risk of mortality, even when stratified according to shock severity. We sought to determine whether the presence of ventricular fibrillation (VF) modified the relationship between CA and mortality in cardiac intensive care unit (CICU) patients.MethodsWe retrospectively analyzed unique Mayo Clinic CICU patients admitted between 2007 and 2015. Society for Cardiovascular Angiography and Intervention (SCAI) shock stages A through E were classified at admission. Hospital mortality in each SCAI shock stage was stratified by the presence of CA, VF CA, or non‐VF CA.ResultsWe included 9,898 patients with a mean age of 68 years (38% females). CA was present in 12%, including 53% with VF CA and 47% with non‐VF CA. Hospital mortality was higher in patients with CA compared to patients without CA (34% vs. 6%; adjusted odds ratio [OR] = 3.1, 95% CI [2.4, 4.0],p < .001), and patients with non‐VF CA had higher hospital mortality than patients with VF CA (44% vs. 25%; adjusted OR = 2.1, 95% CI [1.4, 3.0],p < .001). After adjustment, patients with any CA or non‐VF CA had higher hospital mortality at each SCAI stage, except stage E (all otherp < .05), whereas patients with VF CA did not (allp > .1).ConclusionsCA rhythm modifies the relationship between CA and mortality in CICU patients, when accounting for coma, shock, and organ failure. Outcome studies examining CA in patients with cardiogenic shock need to account for important differences such as CA rhythm.

11514 Background: Cancer pain is a significant problem that impairs patient quality of life and increases healthcare utilization. ePAL is a smartphone application that utilizes patient-reported outcomes (PROs) and artificial intelligence (AI) to optimize cancer pain management. This randomized controlled trial examined the impact of ePAL on cancer pain severity, attitudes toward cancer pain, and healthcare utilization. Methods: Patients with pain from metastatic solid tumors (n = 112) undergoing treatment in a palliative care clinic were randomized to either a control group (n = 56) that received usual care or an intervention group (n = 56) that received ePAL in addition to usual care for 8 weeks. Measures of pain severity (Brief Pain Inventory), attitudes towards cancer treatment (Barriers Questionnaire II) and anxiety (General Anxiety Disorder-7) were assessed. We used repeated measures mixed modeling to assess change in outcome measures over time. We also conducted a chart review to identify pain-related hospital admissions and emergency department (ED) visits and compared risk between study groups. Results: Pain severity (BPI) and negative attitudes toward cancer treatment (BQ-II) decreased significantly for those assigned to ePAL compared to controls (ß = -0.09, p = 0.034 and ß = -0.037, p = 0.042, respectively). Patients assigned to ePAL reported higher anxiety scores compared to controls (ß = 0.21, p = 0.015). Patients assigned to ePAL had significantly fewer pain-related hospital admissions (n = 4 vs. n = 20, per patient risk ratio 0.31, p = 0.018) and fewer pain-related admissions through the ED (n = 2 vs. n = 14, per patient risk ratio 0.18, p = 0.008) compared to control group. Conclusions: To our knowledge, this is the first mobile app to utilize patient reported outcomes and artificial intelligence to significantly decrease pain scores and pain-related hospitalizations in patients with cancer-related pain. Future directions include examining the efficacy of ePAL in settings with limited access to palliative care.

8538 Background: Follicular lymphoma (FL) is a heterogeneous disease with a variable prognosis. Transformation to an aggressive lymphoma is associated with a poor prognosis. Previous studies have identified tumor microenvironment cells such as CD68+ macrophages, PD-1+ and FOXP3+ cells as prognostic in FL. However, results have been conflicting and infrequently address the risk of transformation. In this study we analyzed various components of the microenvironment and their association with transformation. Methods: Patients with FL that later transformed were identified through Mayo Clinic lymphoma database. Tissue specimens at diagnosis were stained with CD68, CD11c, CD21, CXCL13, FOXP3, PD-1 and CD14 and characterized by pattern of location and semi-quantitative cell content. Time to transformation (TTT) and overall survival (OS) were assessed by Kaplan-Meir analysis. Significant variables were further analyzed by cox proportional hazards model. Results: 58 patients were included with a median TTT of 4.7 years (range, 0.4-20). Presence of CD14+ cells vs absence and their location (follicular vs non-follicular) were associated with shorter TTT (4.5 vs 6.2 yrs., p=0.037 and 3.8 vs 5.9 yrs. p= 0.027, respectively). The quantity of PD-1+ cell content was not associated with TTT or OS. However, localization of PD-1 to the follicle compared to diffuse was associated with a longer TTT (6.1 vs 3.6 yrs. p=0.033) and superior OS (9.7 vs 4.6 yrs. p=0.009). On multivariate analysis, the pattern of CD14 and PD-1 staining remained significantly associated with shorter TTT (Table). Conclusions: In follicular lymphoma, a diffuse pattern of PD-1+ cells is associated with inferior TTT and OS. CD14+ cells localized to the follicle is associated with a shorter TTT. After accounting for FLIPI score, both these factors remained significant. These results identify two independent predictors of the rate of transformation in follicular lymphoma and suggest it is location rather than quantity of CD14+ or PD-1+ cells that influence outcomes. [Table: see text]

9581 Background: Previous metastatic breast cancer trials have shown lower overall survival among African American (AA) women. Studies have also shown links between higher comorbidities and lower levels of social support and survival. Whether these factors differ by race and ethnicity is not known. Methods: Breast cancer patients enrolling in a phase III cooperative group metastatic breast cancer trial completed a self-administered survey measuring psychosocial and socio-demographic factors and comorbidities. Results were analyzed by self-identified race/ethnicity and evaluated by other measured variables. Results: 703 out of 799 patients completed the survey (88%). Questions were answered by greater than 95% of participants. The table shows differences broken down by Race/Ethnicity. AA and Hispanic (H) patients were more likely to have trouble paying for medications and have incomes less than 15K per year. AA were less likely to be married, and had lower levels of social support. Differences in income did not mediate these social support differences. Marital status did not mediate lower social support for AA (p=0.79) but did so for whites (p<0.001) Conclusions: Compliance with the questionnaire was quite high. Differences in social support by race were apparent and were mediated by different factors according to race. Future efforts will analyze the impact of these factors on survival and as mediators for potential racial and ethnic differences in survival. [Table: see text]