Increased Scheduled Intravenous Ketorolac After Cesarean Delivery and Its Effect on Opioid Use: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the efficacy of scheduled ketorolac in reducing opioid use after cesarean delivery. METHODS: This was a single-center, randomized, double-blind, parallel-group trial to assess pain management after cesarean delivery with scheduled ketorolac compared with placebo. All patients undergoing cesarean delivery with neuraxial anesthesia received two doses of 30 mg intravenous ketorolac postoperatively and then were randomized to receive four doses of 30 mg of intravenous ketorolac or placebo every 6 hours. Additional nonsteroidal anti-inflammatory drugs were held until 6 hours after the last study dose. The primary outcome was total morphine milligram equivalents (MME) used in the first 72 postoperative hours. Secondary outcomes included the number of patients who used no opioid postoperatively, postoperative pain scores, postoperative change in hematocrit and serum creatinine, and postoperative satisfaction with inpatient care and pain management. A sample size of 74 per group (n=148) provided 80% power to detect a population mean difference in MME of 32.4, with an SD for both groups of 68.7 after accounting for protocol noncompliance. RESULTS: From May 2019 to January 2022, 245 patients were screened and 148 patients were randomized (74 per group). Patient characteristics were similar between groups. The median (quartile 1-3) MME from arrival in the recovery room until postoperative hour 72 was 30.0 (0.0-67.5) for the ketorolac group and 60.0 (30.0-112.5) for the placebo group (Hodges-Lehmann median difference -30.0, 95% CI -45.0 to -15.0, P <.001). In addition, participants who received placebo were more likely to have numeric rating scale pain scores higher than 3 out of 10 ( P= .005). The mean±SD decrease from baseline hematocrit to postoperative day 1 was 5.5±2.6% for the ketorolac group and 5.4±3.5% for the placebo group ( P =.94). The mean±SD postoperative day 2 creatinine was 0.61±0.06 mg/dL in the ketorolac group and 0.62±0.08 mg/dL in the placebo group ( P =.26). Participant satisfaction with inpatient pain control and postoperative care was similar between groups. CONCLUSION: Compared with placebo, scheduled intravenous ketorolac significantly decreased opioid use after cesarean delivery. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT03678675.

Development of a xeno-free non-contact co-culture system for derivation and maintenance of embryonic stem cells using a novel human endometrial cell line.

PURPOSE: Mouse embryonic fibroblast feeder layers (MEF) have conventionally been used to culture and maintain the pluripotency of embryonic stem cells (ESC). This study explores the potential of using a novel human endometrial cell line to develop a non-xeno, non-contact co-culture system for ESC propagation and derivation. Such xeno-free systems may prove essential for the establishment of clinical grade human ESC lines suitable for therapeutic application. METHODS: A novel line of human endometrial cells were seeded in a 6-well dish. Filter inserts containing mouse ESCs were placed on these wells and passaged 2-3 times per week. Inner cell masses derived from mouse blastocysts were also cultured on transwells in the presence of the feeder layer. In both cases, staining for SSEA-1, SOX-2, OCT-4 and alkaline phosphatase were used to monitor the retention of stem cells. RESULTS: ESC colonies retained their stem cell morphology and attributes for over 120 days in culture and 44 passages to date. Inner cell mass derived ESC cultures were maintained in a pluripotent state for 45 days, through 6 passages with retention of all stem cell characteristics. The stem cell colonies expressed stem cell specific markers SSEA-1, Sox 2, Oct-4 and alkaline phosphatase. Upon removal of the human feeder layer, there was a distinct change in cell morphology within the colonies and evidence of ESC differentiation. CONCLUSIONS: Human feeder layers offer a simple path away from the use of MEF feeder cells or MEF conditioned medium for ESC culture. Furthermore, indirect co-culture using porous membranes to separate the two cell types can prevent contamination of stem cell preparations with feeder cells during passaging.