Objectives/Hypothesis Opioid misuse and diversion is a major concern, with a negative impact on both the individual and society. The objective of this study was to perform an evidence‐based systematic review of the efficacy of perioperative analgesic regimens following otologic surgery. Methods Embase, Cochrane Library, and PubMed/MEDLINE databases (January 1, 1947 to June 30, 2018) were searched for studies investigating pain management in otologic surgeries. All studies were assessed for quality and bias using the Cochrane bias tool. Patient demographics, type of surgery, medication class, dose, administration characteristics, pain scores, and adverse events were reported. Results Twenty‐three studies encompassing 1,842 patients met inclusion criteria. In 21.4% of studies, an overall reduction in pain scores was reported when the treatment group included more than one analgesic. Nausea and vomiting were the most common adverse events across all medication types (10.2%), with local anesthetic patients experiencing these side effects most frequently (38.0%). Perioperative acetaminophen was reported to have the fewest adverse drug reactions overall (6.1%), but did not reduce pain scores as much as other modalities, such as nonsteroidal anti‐inflammatory drugs (NSAIDs) or combination analgesics. Conclusions There is evidence that combination analgesics, such as acetaminophen plus codeine, provide superior pain relief to monotherapy analgesics in the perioperative pain management of otologic surgeries. NSAIDs, α‐agonists, and nerve blocks may also be viable single‐therapy options. Further prospective randomized controlled trials into perioperative analgesia for patients undergoing otologic surgery may be helpful in establishing a definitive consensus. Laryngoscope, 130:190–199, 2020
Objectives: Middle third clavicle fractures have long been managed conservatively with immobilization. Some patients, especially those with completely displaced or shortened clavicle fractures are now thought to have increased risk of nonunion or symptomatic malunion. The authors performed a meta-analysis to study the incidence of nonunion and symptomatic malunion and test the hypothesis that surgical fixation of these fractures significantly lowers the risk of these complications. Methods: A search was performed in the PubMed, Embase, and Cochrane Library databases for randomized clinical trials and quasi-experimental trials that compare outcomes of operative and nonoperative management for clavicle fractures that are fully (100%) displaced or have greater than 2 cm of shortening. Pooled patient data were used to construct forest plots for the meta-analysis. Results: Eleven studies including 497 patients who were treated and 457 patients treated conservatively were analyzed. Patients managed operatively had significantly lower relative risk of developing nonunion [0.17 (95% confidence interval 0.08–0.33)] and symptomatic malunion [0.13 (95% confidence interval 0.05–0.37)]. Plate fixation significantly reduced the risk of nonunion, but intramedullary nail fixation did not. There was no difference in Constant–Murley or DASH scores between the 2 treatment groups or in the rate of secondary operative procedures. Conclusions: Patients who undergo operative fixation of displaced middle-third clavicle fractures have a lower incidence of nonunion and symptomatic malunion. The clinical significance of this effect is uncertain, as functional scores were similar in both groups. Further research into the risk factors for nonunion and symptomatic malunion will be necessary to determine which patients benefit from operative fixation. Level of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.
The Crk adaptor protein, a critical modifier of multiple signaling pathways, is overexpressed in many cancers where it contributes to tumor progression and metastasis. Recently, we have shown that Crk interacts with the peptidyl prolyl cis-trans isomerase, Cyclophilin A (CypA; PP1A) via a G 219 P 220 Y 221 (GPY) motif in the carboxyl-terminal linker region of Crk, thereby delaying pY221 phosphorylation and preventing down-regulation of Crk signaling. Here we investigate the physiological significance of the CypA/Crk interaction and query whether CypA inhibition effects Crk signaling in vitro and in vivo. We show that CypA, when induced under conditions of hypoxia, regulates Crk pY221 phosphorylation and signaling in cancer cell lines.Using NMR spectroscopy, we show that CypA binds to the Crk GPY motif via the catalytic PPII domain of CypA, and small molecule non-immunosuppressive inhibitors of CypA (Debio-025) disrupt the CypA-CrkII interaction and restores phosphorylation of Crk Y221. In cultured cell lines, Debio-025 suppresses cell migration, and when administered in vivo in an orthotopic model of triple negative breast cancer, Debio-025 showed anti-tumor efficacy either alone or in combination with anti-PD1 mAb, reducing both tumor volume and metastatic lung dispersion. Furthermore, when analyzed by Nanostring immune profiling treatment of Debio-025 with anti-PD1 mAb increased both T cell signaling and innate immune signaling in TME.Implications: These data suggest that pharmacological inhibition of CypA may provide a promising and unanticipated consequence in cancer biology, in part by targeting the CypA/Crk II axis that regulates cell migration, tumor metastasis, and host anti-tumor immune evasion.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.