Objectives We implement a novel enhanced recovery after surgery (ERAS) protocol with pre‐operative non‐opioid loading, total intravenous anesthesia, multimodal peri‐operative analgesia, and restricted red blood cell (pRBC) transfusions. 1) Compare differences in mean postoperative peak pain scores, opioid usage, and pRBC transfusions. 2) Examine changes in overall length of stay (LOS), intensive care unit LOS, complications, and 30‐day readmissions. Methods Retrospective cohort study comparing 132 ERAS vs. 66 non‐ERAS patients after HNC tissue transfer reconstruction. Data was collected in a double‐blind fashion by two teams. Results Mean postoperative peak pain scores were lower in the ERAS group up to postoperative day (POD) 2. POD0: 4.6 ± 3.6 vs. 6.5 ± 3.5; P = .004) (POD1: 5.2 ± 3.5 vs. 7.3 ± 2.3; P = .002) (POD2: 4.1 ± 3.5 vs. 6.6 ± 2.8; P = .000). Opioid utilization, converted into morphine milligram equivalents, was decreased in the ERAS group (POD0: 6.0 ± 9.8 vs. 10.3 ± 10.8; P = .010) (POD1: 14.1 ± 22.1 vs. 34.2 ± 23.2; P = .000) (POD2: 11.4 ± 19.7 vs. 37.6 ± 31.7; P = .000) (POD3: 13.7 ± 20.5 vs. 37.9 ± 42.3; P = .000) (POD4: 11.7 ± 17.9 vs. 36.2 ± 39.2; P = .000) (POD5: 10.3 ± 17.9 vs. 35.4 ± 45.6; P = .000). Mean pRBC transfusion rate was lower in ERAS patients (2.1 vs. 3.1 units, P = .017). There were no differences between ERAS and non‐ERAS patients in hospital LOS, ICU LOS, complication rates, and 30‐day readmissions. Conclusion Our ERAS pathway reduced postoperative pain, opioid usage, and pRBC transfusions after HNC reconstruction. These benefits were obtained without an increase in hospital or ICU LOS, complications, or readmission rates. Level of Evidence 3 Laryngoscope, 131:E792–E799, 2021

Objectives Evaluate an enhanced recovery after surgery (ERAS)–based free flap management protocol implemented at our center. Study Design Prospective cohort study of patients after implementation of an ERAS-based perioperative care protocol for patients undergoing free flap reconstruction of the head and neck as compared with a historical control group. Setting Tertiary care academic medical center. Participants and Methods All patients undergoing free flap reconstruction were prospectively enrolled in the ERAS protocol group. A retrospective control group was identified by randomly selecting an equivalent number of patients from a records search of those undergoing free flap surgery between 2009 and 2015. Blood transfusion, complications, 30-day readmission rates, intensive care unit (ICU) and hospital length of stay, and costs of hospitalization were compared. Results Sixty-one patients were included in each group. Patients in the ERAS group underwent less frequent flap monitoring by physicians and had lower rates of intraoperative (70.5% vs 86.8%, P = .04) and postoperative (49.2% vs 27.2%, P = .026) blood transfusion, were more likely to be off vasopressors (98.3% vs 50.8%, P < .01) and ventilator support (63.9% vs 9.8%, P < .01) at the conclusion of surgery, and had shorter ICU stays (2.11 vs 3.39 days, P = .017). Length of stay, readmissions, and complication rates did not significantly differ between groups. Conclusion ERAS-based perioperative practices for head and neck free flap reconstruction can reduce time on the ventilator and in the ICU and the need for vasopressors, blood transfusions, and labor-intensive flap monitoring, without adverse effects on outcomes.

Objective To determine the most cost-effective reconstruction method after salvage total laryngectomy. Study Design Cost-effectiveness analysis Setting Tertiary care hospitals with head and neck oncologic and reconstructive surgeons. Subjects and Methods We constructed a Markov-based decision model to compare reconstruction by primary closure to pectoralis flap and free flap after salvage total laryngectomy. The model simulated disease with transition probabilities and health utilities found in primary literature and estimated the average overall cost of each reconstructive method using Medicare billing codes. Effectiveness was compared using quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were performed to scrutinize the conclusions of our model. Reconstruction methods were compared using incremental cost-effectiveness ratios (ICERs). In the United States, less than $150,000 per QALY gained is considered cost-effective (2019 US dollars). Results Our base case analysis revealed that primary closure was less expensive ($44,370) and yielded more QALYs (0.91) than both pectoralis ($45,163, 0.81 QALYs) and free flap ($46,244, 0.85 QALYs), making it the most cost-effective option. Between flaps, free flap was cost-effective over pectoralis flap (ICER = $27,025/QALY gained). Sensitivity analyses showed primary closure as cost-effective 69% of the time over either flap. These conclusions were sensitive to the health utilities (quality of life) of each method of reconstruction. Conclusion Tissue flaps to augment closure after salvage total laryngectomy are not always the most cost-effective reconstructive option. The long-term morbidity of flap surgery oftentimes outweighs the benefit of lowering fistula rates after surgery. Careful consideration must be taken when advising patients of their reconstructive options.

Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae . Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.

Background The prognostic value of lymph node yield (LNY) and lymph node ratio (LNR), or the ratio of number of metastatic LNs to total number dissected, has not been well established in p16‐associated oropharyngeal squamous cell carcinoma (OPSCC). Methods This retrospective cohort study evaluated locoregional disease‐free survival (LRDFS) in 82 patients with p16+ OPSCC who underwent neck dissection at a single institution from 2009 to 2017. LNR and LNY cutoffs were estimated using time‐dependent receiver operator characteristic (ROC) curves. Prognostic significance of these cutoffs was compared with Eighth Edition AJCC Nodal Staging. Results An increased LNR ≥ 0.129 was associated with worse 2‐year LRDFS (66.9% vs 96.8%, P = .005). LNY was not significantly associated with LRDFS (P = .304). An LNR‐based risk model was a better prognosticator than Eighth Edition AJCC Nodal Staging (Harrell's C, 0.9065 vs 0.7668). Conclusions LNR has good prognostic utility in predicting LRDFS in p16+ OPSCC, but further evaluation of this measure is warranted.