Pericapsular nerve group (PENG) block for hip arthroscopy: a randomized, double-blinded, placebo-controlled trial.

INTRODUCTION: Arthroscopic hip surgery is associated with significant postoperative pain. Femoral nerve blocks have been shown to improve postoperative analgesia at the expense of quadriceps weakness. The pericapsular nerve group (PENG) block could be an alternative that may improve postoperative analgesia while preserving quadriceps strength. Our hypothesis was that a PENG block would provide superior postoperative analgesia compared with a sham block following arthroscopic hip surgery. METHODS: Subjects presenting for arthroscopic hip surgery were randomized in a 1:1 ratio to either an ultrasound-guided unilateral, single-injection PENG block (PENG group) with 20 mL of 0.5% ropivacaine or a sham injection with 5 mL of 0.9% normal saline (Sham group) prior to receiving general anesthesia. The primary outcome of this study was worst pain score within 30 min of emergence from anesthesia. Secondary outcomes included opioid consumption, patient satisfaction with analgesia, opioid-related adverse events, and persistent opioid use at 1 week. RESULTS: Sixty-eight subjects, 34 from the PENG group and 34 from the Sham group, completed the study per protocol. Analysis of the primary outcome demonstrated a mean difference in pain scores of -0.79 (95% CI -1.96 to 0.37; p=0.17) between the PENG and Sham groups immediately following surgery. No secondary outcomes showed statistically significant differences between groups. DISCUSSION: This study demonstrates that a preoperative PENG block does not improve analgesia following arthroscopic hip surgery. TRIAL REIGSTRATION NUMBER: NCT04508504.

An Observational Study of the Pharmacokinetics of Surgeon-Performed Intercostal Nerve Blockade With Liposomal Bupivacaine for Posterior-Lateral Thoracotomy Analgesia.

BACKGROUND: Intercostal nerve blocks with liposomal bupivacaine are commonly used for thoracic surgery pain management. However, dose scheduling is difficult because the pharmacokinetics of a single-dose intercostal injection of liposomal bupivacaine has never been investigated. The primary aim of this study was to assess the median time to peak plasma concentration (Tmax) following a surgeon-administered, single-dose infiltration of 266 mg of liposomal bupivacaine as a posterior multilevel intercostal nerve block in patients undergoing posterolateral thoracotomy. METHODS: We chose a sample size of 15 adults for this prospective observational study. Intercostal injection of liposomal bupivacaine was considered time 0. Serum samples were taken at the following times: 5, 15, and 30 minutes, and 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours. The presence of sensory blockade, rescue pain medication, and pain level were recorded after the patient was able to answer questions. RESULTS: Forty patients were screened, and 15 patients were enrolled in the study. Median (interquartile range [IQR]) Tmax was 24 (12) hours (confidence interval [CI], 19.5-28.5 hours) with a range of 15 minutes to 48 hours. The median (IQR) peak plasma concentration (Cmax) was 0.6 (0.3) µg/mL (CI, 00.45-0.74 µg/mL) in a range of 0.3-1.2. The serum bupivacaine concentration was undetectable (<0.2 µg/mL) at 96 hours in all patients. There was significant variability in reported pain scores and rescue opioid medication across the 15 patients. More than 50% of patients had return of normal chest wall sensation at 48 hours. All patients had resolution of nerve blockade at 96 hours. No patients developed local anesthetic toxicity. CONCLUSIONS: This study of the pharmacokinetics of liposomal bupivacaine following multilevel intercostal nerve blockade demonstrates significant variability and delay in systemic absorption of the drug. Peak serum concentration occurred at 48 hours or sooner in all patients. The serum bupivacaine concentration always remained well below the described toxicity threshold (2 µg/mL) during the 96-hour study period.

Peroxisome proliferator-activated receptor-ß/δ inhibits human neuroblastoma cell tumorigenesis by inducing p53- and SOX2-mediated cell differentiation.

Neuroblastoma is a common childhood cancer typically treated by inducing differentiation with retinoic acid (RA). Peroxisome proliferator-activated receptor-ß/δ, (PPARß/δ) is known to promote terminal differentiation of many cell types. In the present study, PPARß/δ was over-expressed in three human neuroblastoma cell lines, NGP, SK-N-BE(2), and IMR-32, that exhibit high, medium, and low sensitivity, respectively, to retinoic acid-induced differentiation to determine if PPARß/δ and retinoic acid receptors (RARs) could be jointly targeted to increase the efficacy of treatment. All-trans-RA (atRA) decreased expression of SRY (sex determining region Y)-box 2 (SOX2), a stem cell regulator and marker of de-differentiation, in NGP and SK-N-BE(2) cells with inactive or mutant tumor suppressor p53, respectively. However, atRA did not suppress SOX2 expression in IMR-32 cells carrying wild-type p53. Over-expression and/or ligand activation of PPARß/δ reduced the average volume and weight of ectopic tumor xenografts from NGP, SK-N-BE(2), or IMR-32 cells compared to controls. Compared with that found with atRA, PPARß/δ suppressed SOX2 expression in NGP and SK-N-BE(2) cells and ectopic xenografts, and was also effective in suppressing SOX2 expression in IMR-32 cells that exhibit higher p53 expression compared to the former cell lines. Combined, these observations demonstrate that activating or over-expressing PPARß/δ induces cell differentiation through p53- and SOX2-dependent signaling pathways in neuroblastoma cells and tumors. This suggests that combinatorial activation of both RARα and PPARß/δ may be suitable as an alternative therapeutic approach for RA-resistant neuroblastoma patients.

Inhibition of testicular embryonal carcinoma cell tumorigenicity by peroxisome proliferator-activated receptor-ß/δ- and retinoic acid receptor-dependent mechanisms.

Peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) has important physiological functions in control of cell growth, lipid and glucose homeostasis, differentiation and inflammation. To investigate the role of PPARß/δ in cancer, stable human testicular embryonal carcinoma cell lines were developed that constitutively express PPARß/δ. Expression of PPARß/δ caused enhanced activation of the receptor, and this significantly decreased proliferation, migration, invasion, anchorage-independent growth, and also reduced tumor mass and volume of ectopic xenografts derived from NT2/D1 cells compared to controls. The changes observed in xenografts were associated with decreased PPARß/δ-dependent expression of proliferating cell nuclear antigen and octamer-binding transcription factor-3/4, suggesting suppressed tumor proliferation and induction of differentiation. Inhibition of migration and invasion was mediated by PPARß/δ competing with formation of the retinoic acid receptor (RAR)/retinoid X receptor (RXR) complex, resulting in attenuation of RARα-dependent matrix metalloproteinase-2 expression and activity. These results demonstrate that PPARß/δ mediates attenuation of human testicular embryonal carcinoma cell progression through a novel RAR-dependent mechanism and suggest that activation of PPARß/δ inhibits RAR/RXR dimerization and represents a new therapeutic strategy.