Does the Levasseur-Merrill Retractor Provide Reliable In Vivo Guidance for the Intraoral Vertical Ramus Osteotomy?

PURPOSE: Levasseur-Merrill retractor (LMR) utilization during the intraoral vertical ramus osteotomy (IVRO) helps initiate the osteotomy approximately 7 mm from the posterior border of the mandible, preventing damage to the inferior alveolar nerve. The purpose of this in vivo study is to evaluate the IVRO placement and the risk of neurosensory deficit (NSD) while using the LMR. METHODS: This prospective case series was conducted at a single tertiary care center. Medical records were reviewed for medical and demographic information. Inclusion criteria were as follows: underwent the IVRO procedure by a single provider from June 2020 to June 2022 and postoperative cone beam computed tomography images. Exclusion criteria were as follows: age less than 16 years, previous mandibular osteotomies, inadequate clinical documentation, or follow-up. The primary outcome variables included the proximal segment width and proximity of the IVRO to the inferior alveolar foramen. The secondary outcome variable was NSD as measured subjectively by 2-point discrimination, sharp versus dull touch, and light touch with von Frey filaments. RESULTS: The 26 subjects (42 operated sides) were 96% female, with an average age of 30.1 years (range 17-54 years). The mean proximal segment width was 10.3 ± 1.7 mm (95% confidence interval: 9.77, 10.83). The mean distance from the posterior border of the inferior alveolar foramen (IAF) to the osteotomy was -0.89 ± 1.7 mm (95% confidence interval: -1.43, -0.35), with negative numbers indicating violation of the IAF. IAF and full bony canal violation occurred in 61.9% and 4.8% of operated sides, respectively. NSD at 6 months postoperatively occurred in the 2 sides that experienced full bony canal violation. CONCLUSIONS: The LMR did not consistently guide the IVRO position within 7 mm from the posterior border of the mandible as previously thought and allows for frequent violation of the IAF. Long-term NSD of the inferior alveolar nerve was infrequent and correlated with violation of the full bony canal.

Does Early Secondary Alveolar Bone Grafting Influence Need for Additional Maxillary Advancement Procedures in Cleft Lip and Palate?

OBJECTIVE: To determine if secondary alveolar bone grafting (SABG) timing in patients with cleft lip and palate (CLP) influences the future need for additional maxillary advancement procedures, particularly Le Fort I osteotomy with rigid external distraction (RED). DESIGN: Retrospective cohort study. Groups were separated by SABG timing: early mixed dentition (ages 68 years) or late mixed dentition (ages 9-11 years). The criterion for RED was negative overjet ≥8 mm, and sufficient dental development for RED. SETTING: Single tertiary care institution. PATIENTS: Patients with CLP that underwent SABG from 2010 to 2015. Exclusion criteria included syndromic conditions, SABG surgery at age >12 years, current age <12 years, and <2 years follow-up. 104 patients were included. MAIN OUTCOME MEASURES: The number of RED candidates and treated patients. RESULTS: There was no statistical difference in the number of RED candidates (P = .0718) nor treated patients (P = .2716) based on SABG timing; stratification by laterality was also insignificant. Early SABG is associated with higher odds of being a RED candidate (pooled, unilateral, bilateral) and treated patient (pooled and unilateral); however, there were no statistically significant associations between SABG timing and the number of RED candidates and treated patients as determined by logistic regression models. CONCLUSION: There is no statistically significant association between SABG timing and the odds of being a RED candidate or treated patient. Future prospective studies are recommended to assess the relationship between SABG timing and maxillary growth in patients with CLP.

Low pH Facilitates Heterodimerization of Mutant Isocitrate Dehydrogenase IDH1-R132H and Promotes Production of 2-Hydroxyglutarate.

Isocitrate dehydrogenase 1 (IDH1) is a key metabolic enzyme for maintaining cytosolic levels of α-ketoglutarate (AKG) and preserving the redox environment of the cytosol. Wild-type (WT) IDH1 converts isocitrate to AKG; however, mutant IDH1-R132H that is recurrent in human cancers catalyzes the neomorphic production of the oncometabolite d-2-hydroxyglutrate (D-2HG) from AKG. Recent work suggests that production of l-2-hydroxyglutarte in cancer cells can be regulated by environmental changes, including hypoxia and intracellular pH (pHi). However, it is unknown whether and how pHi affects the activity of IDH1-R132H. Here, we show that in cells IDH1-R132H can produce D-2HG in a pH-dependent manner with increased production at lower pHi. We also identify a molecular mechanism by which this pH sensitivity is achieved. We show that pH-dependent production of D-2HG is mediated by pH-dependent heterodimer formation between IDH1-WT and IDH1-R132H. In contrast, neither IDH1-WT nor IDH1-R132H homodimer formation is affected by pH. Our results demonstrate that robust production of D-2HG by IDH1-R132H relies on the coincidence of (1) the ability to form heterodimers with IDH1-WT and (2) low pHi or highly abundant AKG substrate. These data suggest cancer-associated IDH1-R132H may be sensitive to physiological or microenvironmental cues that lower pH, such as hypoxia or metabolic reprogramming. This work reveals new molecular considerations for targeted therapeutics and suggests potential synergistic effects of using catalytic IDH1 inhibitors targeting D-2HG production in combination with drugs targeting the tumor microenvironment.