Little is known about the regulation of nonapoptotic cell death. Using massive insertional mutagenesis of haploid KBM7 cells we identified nine genes involved in small-molecule-induced nonapoptotic cell death, including mediators of fatty acid metabolism (ACSL4) and lipid remodeling (LPCAT3) in ferroptosis. One novel compound, CIL56, triggered cell death dependent upon the rate-limiting de novo lipid synthetic enzyme ACC1. These results provide insight into the genetic regulation of cell death and highlight the central role of lipid metabolism in nonapoptotic cell death.

No abstract

No abstract

Background: The purpose of this study was to assess the efficacy of biodegradable, electrospun poly(ε-caprolactone) nanofiber nerve conduits in improving nerve regeneration. Methods: The authors used a rat forelimb chronic denervation model to assess the effects of poly(ε-caprolactone) conduits on improving nerve regeneration and upper extremity function. Three groups of rats were examined: (1) negative-control animals (n = 5), which underwent 8 weeks of median nerve chronic denervation injury followed by repair with no conduit; (2) experimental animals (n = 5), which underwent 8 weeks of median nerve chronic denervation followed by repair and poly(ε-caprolactone) nerve conduit wrapping of the nerve coaptation site; and (3) positive-control animals (n = 5), which were naive controls. All animals underwent compound muscle action potential and functional testing. At 14 weeks after repair, the median nerve and flexor muscles were harvested for histologic analysis. Results: Histomorphometric analysis of regenerating median nerves demonstrated augmented axonal regeneration in experimental versus negative control animals (total axon count, 1769 ± 672 versus 1072 ± 123.80; p = 0.0468). With regard to functional recovery, experimental and negative-control animals (1.67 ± 0.04 versus 0.97 ± 0.39; p = 0.036) had regained 34.9 percent and 25.4 percent, respectively, of baseline hand grip strength at 14 weeks after repair. Lastly, less collagen deposition at the nerve coaptation site of experimental animals was found when compared to control animals (p < 0.05). Conclusion: Biodegradable, poly(ε-caprolactone) nanofiber nerve conduits can improve nerve regeneration and subsequent physiologic extremity function in the setting of delayed nerve repair by decreasing the scar burden at nerve coaptation sites.

Background: Surgical site infection (SSI) after open cranial vault reconstruction (CVR), while relatively uncommon, has received little attention in the literature to date. Here, the authors report our institution's experience with the perioperative management of infectious complications following CVR for craniosynostosis and present the first systematic review of the literature on this topic. Methods: The authors performed a retrospective chart review for patients with syndromic and nonsyndromic craniosynostosis who underwent open CVR between 1990 and 2015 at a single institution to determine predictors of SSIs and a systematic review of studies that evaluated for SSI after CVR to ascertain the pooled incidence of SSI, common infectious organisms, and prophylactic antibiotic protocols. Results: Out of 548 primary and 163 secondary CVR cases at our institution, 6 primary reconstruction patients (1.09%) and 9 secondary reconstruction patients (5.52%) developed an SSI requiring extended hospital stay or readmission (P <0.001); overall infection rate was 2.11%. Streptococcus and Staphylococcus species were the most common organisms isolated. On multivariate analysis, syndromic status conferred more than 7 times greater odds of SSI (OR 7.7, P = 0.023). Pooled analysis of the literature yielded an overall SSI rate of 1.05% to 2.01%. In contrast to our institutional findings, the most common organisms reported were Candida species and Pseudomonas aeruginosa. The most common prophylactic antibiotic protocol was a first-generation cephalosporin for 24 to 72 hours post-operatively. Conclusions: Patients undergoing secondary reconstruction have higher infection rates after CVR, and syndromic status is an important predictor of infection when controlling for other patient factors. Our literature review reveals nosocomial organisms to be the most commonly reported source of infection, though this is contrary to our institutional findings of skin flora being most common. Antibiotic prophylaxis varies institutionally.

Open craniosynostosis repair is associated with high levels of pain and low utilization of nonopioid analgesics. Strategies to improve pain, decrease emesis and LOS include implementation of multimodal analgesia period and avoidance of enteral medications in the first 24 hours after surgery.

Background: Developing effective strategies to manage perioperative pain remains a focus of cleft care. The present study’s purpose was to systematically review perioperative pain control strategies for cleft lip and palate repair. Methods: A systematic review and meta-analysis of randomized controlled trials was performed. Primary outcomes included pain scale scores and time to analgesia failure. Cohen d normalized effect size permitted comparison between studies, and a fixed-effects model was used for analysis. I2 and Q-statistic p values were calculated. Results: Twenty-three studies were included: eight of 23 studies provided data for meta-analytic comparison. Meta-analyses evaluated the efficacy of intraoperative nerve blocks on postoperative pain management. Meta-analysis included a total of 475 treatment and control patients. Cleft lip studies demonstrated significantly improved pain control with a nerve block versus placebo by means of pain scale scores (p < 0.001) and time to analgesia failure (p < 0.001). Measurement of effect size over time demonstrated statistically significant pain relief with local anesthetic. Palatoplasty studies showed significantly improved time to analgesia failure (p < 0.005) with maxillary and palatal nerve blocks. Multiple studies demonstrated an opioid-sparing effect with the use of local anesthetics and other nonopioid medications. Techniques for nerve blocks in cleft lip and palate surgery are reviewed. Conclusions: The present systematic review and meta-analysis of randomized controlled studies demonstrates that intraoperative nerve blocks for cleft lip and palate surgery provide effective pain control. Opioid-sparing effects were appreciated in multiple studies. Intraoperative nerve blocks should be considered in all cases of cleft lip and palate repair to improve postoperative pain management. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

The use of CAD/CAM technology allows for accurate intraoperative dural venous sinus localization during reconstructive surgery for craniosynostosis and enhances operative efficiency and surgeon confidence while minimizing the risk of patient morbidity.