Howe, Carol

512 Background: The tumor microenvironment in PDA is heterogeneous and immunosuppressive given the presence of regulatory T cells and exhausted effector T cells. Despite the upsurge of effective immunotherapeutic agents (IA) in other tumor types, the role in PDA remains unknown. We conducted a meta-analysis of IA in PDA. Methods: Following PRISMA guidelines, we searched PubMed/MEDLINE, Elsevier/Embase, Wiley/Cochrane Library and ClinicalTrials.gov. Articles were selected per the following criteria: (1) Study participants had a diagnosis of PDA; (2) An IA was used in the trial. Titles, abstracts and full text articles were reviewed by 2 independent reviewers; disagreements were resolved by a third. Data extraction and analysis were performed by 3 independent reviewers. Descriptive analysis, mean, median, confidence interval and forest plots were used for statistical analysis. Results: We found 20,792 studies through the database, 16,105 remained after duplicates were removed and 15,889 were excluded due to irrelevance. Strict inclusion criteria were applied to the full text of 216 articles. The most common reason for exclusion were conference abstracts (44%) and ongoing trials (16%). Fifty-four trials (39 metastatic (met), 12 adjuvant (Ad) and 3 neoadjuvant (nAd) met criteria for further analysis. Age range was 27-86 (median 61) and 52.3% were males. IA included cytokine therapy (33%), peptide vaccines (22%), dendritic cell vaccine (13%), oncolytic viruses (9%), CTLA-4 inhibitors (2%) and others. IA in met-PDA had a median overall survival (mOS) of 8.1 months (ms) and a disease control rate (DCR) of 55.4% (95% CI, 51.85-58.95). There was no statistical difference in DCR among IA subtypes (range 49-60%) (p = 0.22). The mOS of Ad-PDA trials was 25 ms (historically comparable to gemcitabine, p = 0.75) and 18 ms for nAd-PDA. The most common Gr1/2 toxicities were skin reactions, fever, and chills and Gr3/4 were cytopenias, diarrhea, and mucositis. One death occurred due to neutropenic sepsis. Conclusions: IA demonstrates modest efficacy in the treatment of met-PDA albeit exhibits a favorable toxicity profile. Many trial results are available only in abstract format and some are ongoing.

Background Accurate determination of right ventricular ejection fraction (RVEF) is challenging because of the unique geometry of the right ventricle. Tricuspidannular plane systolic excursion (TAPSE) and fractional area change (FAC) are commonly used echocardiographic quantitative estimates of RV function. Cardiac MRI (CMRI) has emerged as the gold standard for assessment of RVEF. We sought to summarise the available data on correlation of TAPSE and FAC with CMRI-derived RVEF and to compare their accuracy. Methods We searched PubMed, EMBASE, Web of Science, CINAHL, ClinicalTrials.gov and the Cochrane Library databases for studies that assessed the correlation of TAPSE or FAC with CMRI-derived RVEF. Data from each study selected were pooled and analysed to compare the correlation coefficient of TAPSE and FAC with CMRI-derived RVEF. Subgroup analysis was performed on patients with pulmonary hypertension. Results Analysis of data from 17 studies with a total of 1280 patients revealed that FAC had a higher correlation with CMRI-derived RVEF compared with TAPSE (0.56vs0.40, P=0.018). In patients with pulmonary hypertension, there was no statistical difference in the mean correlation coefficient of FAC and TAPSE to CMR (0.57vs0.46, P=0.16). Conclusions FAC provides a more accurate estimate of RV systolic function (RVSF) compared with TAPSE. Adoption of FAC as a routine tool for the assessment of RVSF should be considered, especially since it is also an independent predictor of morbidity and mortality. Further studies will be needed to compare other methods of echocardiographic measurement of RV function.

Objective Previous studies have suggested that statin pretreatment prevents contrast-induced nephropathy (CIN). However, single randomised trials are limited in their number of patients. This meta-analysis aims to assess the role of statin use in CIN prevention, as well as to determine patient subgroups that will benefit from statin pre-treatment. Methodology We searched PubMed, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomised controlled trials (RCT) comparing statin pretreatment versus placebo for preventing CIN. Our main outcome was the risk of CIN within 1–5 days after contrast administration. Results Data analysed from nine randomised studies with a total of 5143 patients, where 2559 received statins and 2584 received placebo, showed that statin pretreatment was associated with significant reduction in risk of CIN (MH-RR=0.47, 95% CI 0.34 to 0.64, Z=4.49, p<0.00001). This beneficial effect of statin was also seen in patients with baseline renal impairment (MH-RR=0.46, 95% CI 0.29 to 0.72, p=0.0008) and also those who were cotreated with NAC (MH-RR=0.46, 95% CI 0.25 to 0.83, p=0.01). Conclusions Statin pretreatment leads to significant reduction in CIN, and should be strongly considered in all patients who are planned for diagnostic and interventional procedures involving contrast-media administration.