Temporal trends in pregnancy-associated stroke and its outcomes among women with hypertensive disorders of pregnancy

Funding PW is funded by a NIHR Transitional Research Fellowship. CCG is part-funded by West Midlands ARC. LCC is funded by a NIHR Professorship (RP-2014-05-019). This paper presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no involvement in the conduct of this research.Peer reviewedPublisher PD

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

In-Hospital Complications in Pregnant Women With Current or Historical Cancer Diagnoses

Objective To assess the temporal trends, patient characteristics and comorbidities, and in-hospital cardiovascular and obstetric complications and outcomes of pregnant women with current or historical cancer diagnosis at the time of admission for delivery. Patients and Methods We analysed delivery hospitalisations with or without current or historical cancer between January 1, 2004 and December 31, 2014 from the United States National Inpatient Sample database. Results We included 43,132,097 delivery hospitalisations with no cancer, 39,118 with current cancer and 67,336 with historical diagnosis of cancer. The five most common types of current cancer were haematological, thyroid, cervical, skin and breast cancer. Women with current and historical cancer were older (29 and 32 vs. 27 years) and incurred higher hospital costs ($4,131 and$4,078 vs. $3,521), compared to women without cancer. Most of the cancer types were associated with preterm birth (haematological: adjusted odds ratio (aOR) 1.48, 95% confidence interval (CI) 1.35-1.62; cervical: aOR 1.47, 95% CI 1.32-1.63; breast: aOR 1.93, 95% CI 1.72-2.16). Current haematological cancer was associated with the highest risk of peripartum cardiomyopathy (aOR 12.19, 95% CI 7.75-19.19), all-cause mortality (aOR 6.50, 95% CI 2.22-19.07), arrhythmia (aOR 3.82, 95% CI 2.04-7.15) and postpartum haemorrhage (aOR 1.31, 95% CI 1.11-1.54). Having current or historical cancer diagnosis did not confer additional risk for stillbirth; however metastases increased the risk of maternal mortality and preterm birth. Conclusion Women with current or historical diagnosis of cancer at delivery have more comorbidities compared to women without cancer. Clinicians should communicate the risks of multi-system complications to this complex patient group

Relation of Extracardiac Vascular Disease and Outcomes in Patients With Diabetes (1.1 Million) Hospitalized for Acute Myocardial Infarction

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In-Hospital Complications in Pregnancies Conceived by Assisted Reproductive Technology

BACKGROUND: Assisted reproductive technology (ART) has emerged as a common treatment option for infertility, a problem that affects an estimated 48 million couples worldwide. Advancing maternal age with increasing prepregnancy cardiovascular risk factors, such as chronic hypertension, obesity, and diabetes, has raised concerns about pregnancy complications associated with ART. However, in‐hospital complications following pregnancies conceived by ART are poorly described. METHODS AND RESULTS: To assess the patient characteristics, obstetric outcomes, vascular complications and temporal trends of pregnancies conceived by ART, we analyzed hospital deliveries conceived with or without ART between January 1, 2008, and December 31, 2016, from the United States National Inpatient Sample database. We included 106 248 deliveries conceived with ART and 34 167 246 deliveries conceived without ART. Women who conceived with ART were older (35 versus 28 years; P<0.0001) and had more comorbidities. ART‐conceived pregnancies were independently associated with vascular complications (acute kidney injury: adjusted odds ratio [aOR], 2.52; 95% CI 1.99–3.19; and arrhythmia: aOR, 1.65; 95% CI, 1.46–1.86), and adverse obstetric outcomes (placental abruption: aOR, 1.57; 95% CI, 1.41–1.74; cesarean delivery: aOR, 1.38; 95% CI, 1.33–1.43; and preterm birth: aOR, 1.26; 95% CI, 1.20–1.32), including in subgroups without cardiovascular disease risk factors or without multifetal pregnancies. Higher hospital charges ($18 705 versus$11 983; P<0.0001) were incurred compared with women who conceived without ART. CONCLUSIONS: Pregnancies conceived by ART have higher risks of adverse obstetric outcomes and vascular complications compared with spontaneous conception. Clinicians should have detailed discussions on the associated complications of ART in women during prepregnancy counseling