Ochsner Medical Center

About: Ochsner Medical Center is a healthcare organization based out in New Orleans, Louisiana, United States. It is known for research contribution in the topics: Population & Heart failure. The organization has 980 authors who have published 1159 publications receiving 49961 citations. The organization is also known as: Ochsner Hospital & Ochsner Foundation Hospital.

IDDF2019-ABS-0131 Algorithms using noninvasive tests can accurately identify patients with advanced fibrosis due to NASH: data from the STELLAR clinical trials

Abstract: Background There is a major unmet need for accurate, readily available, noninvasive tests (NITs) to identify patients with advanced fibrosis due to NASH. Our goal was to evaluate sequential NIT algorithms to minimize the requirement for biopsy and improve accuracy overuse of single tests. Methods The STELLAR studies (NCT03053050, NCT03053063) enrolled NASH patients with bridging fibrosis (F3) or compensated cirrhosis (F4). Baseline liver biopsies were read using the NASH CRN fibrosis classification and noninvasive fibrosis markers: FIB-4 index, ELF test, and FibroScan® (FS). The performance of these tests to discriminate advanced fibrosis was evaluated using AUROCs with 5-fold cross-validation repeated 100x. Thresholds were obtained by maximizing specificity given ≥85% sensitivity. The cohort was divided (80%/20%) into evaluation/validation sets. The evaluation set was further stratified 250x into training and test sets (66%/33%). Optimal thresholds were derived as the average across training sets, and applied sequentially (FIB-4 followed by ELF and/or FS) to the validation set. Data are from an interim analysis on 26 July 2018. Results All patients with available liver histology (N=3202, 71% F3-F4) and NIT results were included. While single tests were able to discriminate advanced fibrosis (AUROCs of 0.78, 0.80, and 0.80 for FIB-4, ELF, and FS in validation cohort), up to 32% of patients had an indeterminate result. Using thresholds derived from STELLAR data, FIB-4 followed by FS or ELF in those with indeterminate FIB-4 values (1.23 to 2.1) reduced indeterminate results to as low as 13% (table 1). Published NIT thresholds yielded similar results (data not shown). Adding a third test (FIB-4 then ELF then FS) reduced the rate of indeterminate results to 8%. Misclassification occurred at rates similar to biopsy (15–21%). The majority of misclassifications (63–81%) were false negatives; among false positive cases (19–27% of misclassifications) up to 70% had F2 fibrosis. Conclusions FIB-4 followed by ELF and/or FS nearly eliminated the need for liver biopsy and accurately identified patients with advanced fibrosis due to NASH with misclassification rates similar to liver biopsy.

Measuring Carotid Revascularization Quality

Abstract: > Holy Grail: something that you want very much but that is very hard to get or achieve > > —Merriam-Webster Because US health care pivots from volume-based to value-based strategies, there is growing emphasis on optimizing quality, safety, and appropriate utilization. Accordingly, to improve, we must be able to measure our performance. In this issue of Circulation: Cardiovascular Interventions , Kuehnl et al provide a timely publication, from the German national database, that informs our quest for the Holy Grail of measureable quality and safety for internal carotid artery revascularization.1 See Article by Kuehnl et al The authors analyzed 182 033 procedures involving internal carotid artery revascularization, performed in Germany between 2009 and 2014. Because of mandatory reporting requirements, 99.1% of the data were available for analysis. They arbitrarily split the German hospitals into quintiles based on the case volumes for carotid endarterectomy (CEA; n=161 448) and carotid stenting (CAS; n=17 575) and then looked for correlations between hospital case volume and their safety end point, in-hospital death, and stroke. Not surprisingly, their data, consistent with other observations,2 confirmed an inverse relationship between hospital CEA case volume and inpatient death and stroke, but, similar to other reports,3 failed to confirm an inverse safety relationship for CAS hospital volume. This is counterintuitive. A high-risk, complex …

Dosimetry in Clinical Radiopharmaceutical Therapy of Cancer: Practicality Versus Perfection in Current Practice.

Abstract: The use of radiopharmaceutical therapies (RPTs) in the treatment of cancers is growing rapidly, with more agents becoming available for clinical use in last few years and many new RPTs being in development. Dosimetry assessment is critical for personalized RPT, insofar as administered activity should be assessed and optimized in order to maximize tumor-absorbed dose while keeping normal organs within defined safe dosages. However, many current clinical RPTs do not require patient-specific dosimetry based on current Food and Drug Administration-labeled approvals, and overall, dosimetry for RPT in clinical practice and trials is highly varied and underutilized. Several factors impede rigorous use of dosimetry, as compared with the more convenient and less resource-intensive practice of empiric dosing. We review various approaches to applying dosimetry for the assessment of activity in RPT and key clinical trials, the extent of dosimetry use, the relative pros and cons of dosimetry-based versus fixed activity, and practical limiting factors pertaining to current clinical practice.

Abstract 758: Comparative pharmacokinetics for 4-demethyl-4-cholesteryloxy- carbonylpenclomedine (DM-CHOC-PEN) in humans

Abstract: Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a polychlorinated pyridine cholesteryl carbonate, which is active vs. intracranially (IC) implanted human xenograft models - U251 and D54 glioblastoma and MX-1 breast cancer (%LTS/CR): +29/25 and +20/17, resp. and has a MOA via alkylation of DNA @ N7 - guanine (CCP, 64, 829, 2009). DM-CHOC-PEN's preclinical rodent single IV dose toxicity studies documented the following landmark values: for mice - LD10/50 136/385 mg/kg; & for rats - LD10 100 mg/kg. DM-CHOC-PEN is metabolized to 4-demethyl-PEN (DM-PEN) and cholesterol. The DLT in rats was hypercholesteremia - 2nd to release of cholesterol from the oxycarbonate moiety. The LDL-cholesterol was increased 30 fold at doses of 200 and 300 mg/kg, which returned to normal values - predominantly as the HDL-cholesterol by Day 15. Plasma and erythrocyte DM-CHOC-PEN and metabolites DM-PEN/cholesterol were assayed vs. time by HPLC. Overall, PK values in rats revealed the following profile for DM-CHOC-PEN @ 100 mg/kg: AUC o-t = 1.05 mg (h/L), T1/2β = 0.51 (h), T1/2β = 2.48 (h) & CL = 3.04 (L/h) [a two compartment model]. The AUC was linear for 100, 200, 300 mg/kg doses. There were no differences between males and females. For the Phase I clinical trial (IND 68,876), the calculated (from mice) initial single dose for DM-CHOC-PEN was 39 mg/m2 administrated IV q 21-days with 40% dose escalations q 3-cycles until SLTs were identified. To date, doses of 39, 55, 70 mg/m2 have been administered to patients without toxicity. DM-CHOC-PEN PK modeling revealed a central compartment (cpt) which released the drug into a peripheral compartment (pct) with CL - 0.141L/h, T1/2 α - 0.63 h & Tα - 24.1 h. DM-CHOC-PEN & DM-PEN showed an important rebound phenomenon @ ∼ 50 hours post-infusion with Trelease 26.7h (for both).Same phenomenon is observed in rbcs (estimation using Monolix 3.2). DM-CHOC-PEN and DM-PEN were detected for 3 and 15 days, resp., bound to rbcs (after 70 mg/m2); DM-CHOC-PEN was also detected in the urine (Cmax=17.5 µg/mL) until day 15. Similar to rats, the total lipid profiles (cholesterol and triglycerides) for the patients were erratic during the 3-h IV infusion period (2o to the lipid emulsion vehicle) and then returned to pre-treatment values after 24 h; triglycerides most significantly affected. In 1-patient, DM-CHOC-PEN could be identified in sarcoma tissue metastatic to the spine in 190 ng/g quantities, which was obtained 21-days post IV infusion with 39 mg/m2. Five (5) patients have been treated to date; no hematological, neurotoxic or psychological alterations have been identified. Thus, DM-CHOC-PEN is well tolerated with manageable toxicities to date; the trial continues. An update on patient responses/toxicities will be presented. Comparative PK profiles of DM-CHOC PEN and metabolite in plasma, RBC and urine are analyzed and will be presented here. Supported by NCI/SBIR grant - 1R43CA132257. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 758. doi:1538-7445.AM2012-758