Our data suggest that vestibular rehabilitation increases aVOR gain during active head rotation independent of peripheral aVOR gain recovery.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have poor efficacy in head and neck squamous cell carcinoma (HNSCC). Because the insulin-like growth factor-1 receptor (IGF1R) generates potent prosurvival signals and has been implicated in therapeutic resistance, its ability to induce resistance to EGFR-TKIs was studied in vitro. Five HNSCC cell lines demonstrated reduced sensitivity to the EGFR-TKI gefitinib when the IGF1R was activated. In SCC-25 and Cal27 cells, gefitinib inhibited basal and EGF-stimulated EGFR, Erk and Akt phosphorylation and reduced cell number. This correlated with initiation of apoptosis based on a 4-fold increase poly-(ADP-ribose) polymerase (PARP) cleavage and a 2.5-fold increase in Annexin V positivity. The apoptotic response and reduction in cell number were blocked by IGF1R activation, which resulted in phosphorylation of both Erk and Akt. In both cell lines, IGF1R-induced Erk but not Akt activation was eliminated by gefitinib. IGF1R-induced gefitinib resistance was unaffected by MEK inhibition with U0126, but was partially impaired by inhibition of phosphatidylinositol 3′-kinase (PI3K) with LY294002. The IGF1R-TKI PQ401 inhibited growth of SCC-25 and Cal27 cells alone and also acted synergistically with gefitinib. Thus the IGF1R can make HNSCC cells resistant to EGFR-TKI treatment via a prosurvival mechanism. Of 8 studied, all HNSCC tumor samples expressed the IGF1R and 5 demonstrated detectable IGF1R phosphorylation, suggesting that this receptor may be relevant in vivo, and thus combined EGFR/IGF1R inhibition may be necessary in some patients for effective targeted molecular therapy.

Immediate postoperative extubation in the OR following head and neck microvascular free tissue transfer reduces ICU stay, anxiolytic use, restraint use, and incidence of pneumonia without an increase in flap- or wound-related complications.

The cullin RING E3 ubiquitin ligase 4 (CRL4) with its substrate receptor CDT2 (CRL4-CDT2) is emerging as a critical regulator of DNA replication through targeting CDT1, SET8, and p21 for ubiquitin-dependent proteolysis. The aberrant increased stability of these proteins in cells with inactivated CRL4-CDT2 results in DNA rereplication, which is deleterious to cells due to the accumulation of replication intermediates and stalled replication forks. Here, we demonstrate that CDT2 is overexpressed in head and neck squamous cell carcinoma (HNSCC), and its depletion by siRNA inhibits the proliferation of human papilloma virusnegative (HPV-ve) HNSCC cells primarily through the induction of rereplication. Treatment of HNSCC with the NEDD8-activating enzyme inhibitor pevonedistat (MLN4924), which inhibits all cullin-based ligases, induces significant rereplication and inhibits HNSCC cell proliferation in culture and HNSCC xenografts in mice. Pevonedistat additionally sensitizes HNSCC cells to ionizing radiation (IR) and enhances IR-induced suppression of xenografts in mice. Induction of rereplication via CDT2 depletion, or via the stabilization or activation of CDT1, also radiosensitizes HNSCC cells. Collectively, these results demonstrate that induction of rereplication represents a novel approach to treating radioresistant HNSCC tumors and suggest that pevonedistat may be considered as an adjuvant for IR-based treatments.

Complications from repair of mandible fractures are rare; it is difficult to detect significant variables that may impact outcomes. We found no relationship between complications and timing to repair.