Objectives: Enhanced recovery after surgery (ERAS) protocols were first developed in colorectal surgery and sought to standardize patient care. There have been several studies in the head and neck surgical literature looking at outcomes after ERAS protocol, but no studies focusing on narcotic use and length of stay. This study aimed to evaluate narcotic usage and length of stay, in addition to several other outcomes, following the implementation of an ERAS protocol.Methods: A head and neck-specific ERAS protocol was implemented at this tertiary care center beginning July 2017. A retrospective cohort study was performed comparing this cohort to that of a retrospective control group. Outcomes included mean morphine equivalent dose, mean pain score, and percentage of patients prescribed narcotics on discharge. Secondary outcomes included ICU and total length of stay.Results: The mean morphine equivalent dose (MED) administered within 72 hours postoperatively was significantly lower in the ERAS group (17.5 AE 46.0 mg vs. 82.7 AE 116.1 mg, P < .001). Average postoperative pain scores in the first 72 hours were lower in the ERAS group (2.6 AE 1.8 vs. 3.6 AE 1.9; P < .001). The average length of stay was shorter for ERAS patients (7.8 AE 4.8 vs. 9.7 AE 4.7 days, P = .008); however, there was no significant difference in ICU length of stay.Conclusion: Following implementation of an ERAS protocol, patients undergoing head and neck surgery had decreased narcotic use in the immediate postoperative period and at discharge, while also demonstrating improved postoperative analgesia.

IMPORTANCEAn increase in narcotic prescription patterns has contributed to the current opioid epidemic in the United States. Opioid-sparing perioperative analgesia represents a means of mitigating the risk of opioid dependence while providing superior perioperative analgesia.OBJECTIVE To assess whether multimodal analgesia (MMA) is associated with reduced narcotic use and improved pain control compared with traditional narcotic-based analgesics at discharge and in the immediate postoperative period after free flap reconstructive surgery. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study assessed a consecutive sample of 65 patients (28 MMA, 37 controls) undergoing free flap reconstruction of a through-and-through mucosal defect within the head and neck region at a tertiary academic referral center from June 1, 2017, to November 30, 2018. Patients and physicians were not blinded to the patients' analgesic regimen. Patients' clinical courses were followed up for 30 days postoperatively.INTERVENTIONS Patients were administered a preoperative, intraoperative, and postoperative analgesia regimen consisting of scheduled and as-needed neuromodulating and anti-inflammatory medications, with narcotic medications reserved for refractory cases. Control patients were administered traditional narcotic-based analgesics as needed.MAIN OUTCOMES AND MEASURES Narcotic doses administered during the perioperative period and at discharge were converted to morphine-equivalent doses (MEDs) for comparison. Postoperative Defense and Veterans Pain Rating Scale pain scores (ranging from 0 [no pain] to 10 [worst pain imaginable]) were collected for the first 72 hours postoperatively as a patient-reported means of analyzing effectiveness of analgesia.RESULTS A total of 28 patients (mean [SD] age, 64.1 [12.3] years; 17 [61%] male) were included in the MMA group and 37 (mean [SD] age, 65.0 [11.0] years; 22 [59%] male) in the control group. The number of MEDs administered postoperatively was 10.0 (interquartile range [IQR], 2.7-23.1) in the MMA cohort and 89.6 (IQR, 60.0-104.5) in the control cohort (P < .001). Mean (SD) Defense and Veterans Pain Rating Scale pain scores postoperatively were 2.05 (1.41) in the MMA cohort and 3.66 (1.99) in the control cohort (P = .001). Median number of MEDs prescribed at discharge were 0 (IQR, 0-18.8) in the MMA cohort and 300.0 (IQR, 262.5-412.5) in the control cohort (P < .001). CONCLUSIONS AND RELEVANCEThe findings suggest that after free flap reconstruction, MMA is associated with reduced narcotic use at discharge and in the immediate postoperative period and with superior analgesia as measured by patient-reported pain scores. Patients receiving MMA achieved improved pain control, and the number of narcotic prescriptions in circulation were reduced.LEVEL OF EVIDENCE 3.

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The fact that several vernal pool restoration and creation attempts in eastern Pennsylvania and New Jersey have been paired with conservation of natural pools in the same area provided a valuable research opportunity to compare amphibian habitat quality between project sites and natural reference pools. To measure desired outcomes, we used successful reproduction and metamorphosis of two vernal pool indicator species, the wood frog and spotted salamander. Although many previous studies indicate that restored and created pools rarely replace function lost in the destruction of natural pools, success of vernal pool indicator species was not necessarily related to pool type in this study. Results indicate a strong correlation between reproductive success for both species and vernal pool size (i.e. mean depth and volume), regardless of pool type. Although overall survival rates of wood frog larvae were significantly higher in natural pools with hydroperiods between 12 and 35 weeks, wood frogs were also successful in one restored and one created vernal pool. Salamander survival rates were highest in two natural and two created pools, which had in common both greater volumes and higher proportions of forest land cover in the surrounding 1,000 m. The documented success of vernal pool indicator species in two well-established created pools demonstrates that pool creation can sometimes restore communities and ecological functions lost, especially when nearby natural pools are degraded or destroyed. Implications for Practice• Success of amphibian breeding and metamorphosis in vernal pools is not necessarily related to pool type, but quality of mitigation attempts is highly variable. • Well-established created vernal pools with high-quality postbreeding habitat can be beneficial to amphibian populations in the long term. • Practitioners aiming to restore functional habitat for vernal pool species should focus on the relationship between pool volume and hydroperiod, surrounding forest cover, and proximity to natural pools, as these factors appear to be more closely related to amphibian success than others. • Vernal pool restoration and creation projects should be accompanied by extensive monitoring studies that include measures of success beyond amphibian egg mass counts since vernal pools with abundant egg masses do not always have high overall survival rates.

FKBP65 is an endoplasmic reticulum (ER)-localized chaperone and rotamase, with cargo proteins that include tropoelastin and collagen. In humans, mutations in FKBP65 have recently been shown to cause a form of osteogenesis imperfecta (OI), a brittle bone disease resulting from deficient secretion of mature type I collagen. In this work, we describe the rapid proteolysis of FKBP65 in response to ER stress signals that activate the release of ER Ca 2+ stores. A large-scale screen for stress-induced cellular changes revealed FKBP65 proteins to decrease within 6-12 h of stress activation. Inhibiting IP 3 R-mediated ER Ca 2+ release blocked this response. No other ER-localized chaperone and folding mediators assessed in the study displayed this phenomenon, indicating that this rapid proteolysis of folding mediator is distinctive. Imaging and cellular fractionation confirmed the localization of FKBP65 (72 kDa glycoprotein) to the ER of untreated cells, a rapid decrease in protein levels following ER stress, and the corresponding appearance of a 30-kDa fragment in the cytosol. Inhibition of the proteasome during ER stress revealed an accumulation of FKBP65 in the cytosol, consistent with retrotranslocation and a proteasome-based proteolysis. To assess the role of Ca 2+ -binding EF-hand domains in FKBP65 stability, a recombinant FKBP65-GFP construct was engineered to ablate Ca 2+ binding at each of two EF-hand domains. Cells transfected with the wild-type construct displayed ER localization of the FKBP65-GFP protein and a proteasome-dependent proteolysis in response to ER stress. Recombinant FKBP65-GFP carrying a defect in the EF1 Ca 2+ -binding domain displayed diminished protein in the ER when compared to wild-type FKBP65-GFP. Proteasome inhibition restored mutant protein to levels similar to that of the wild-type FKBP65-GFP. A similar mutation in EF2 did not confer FKBP65 proteolysis. This work supports a model in which stress-induced changes in ER Ca 2+ stores induce the rapid proteolysis of FKBP65, a chaperone and folding mediator of collagen and tropoelastin. The destruction of this protein may identify a cellular strategy for replacement of protein folding machinery following ER stress. The implications for stress-induced changes in the handling of aggregateprone proteins in the ER-Golgi secretory pathway are discussed.