Spatial subsetting enables integrative modeling of oral squamous cell carcinoma multiplex imaging data.

Oral squamous cell carcinoma (OSCC), a prevalent and aggressive neoplasm, poses a significant challenge due to poor prognosis and limited prognostic biomarkers. Leveraging highly multiplexed imaging mass cytometry, we investigated the tumor immune microenvironment (TIME) in OSCC biopsies, characterizing immune cell distribution and signaling activity at the tumor-invasive front. Our spatial subsetting approach standardized cellular populations by tissue zone, improving feature reproducibility and revealing TIME patterns accompanying loss-of-differentiation. Employing a machine-learning pipeline combining reliable feature selection with multivariable modeling, we achieved accurate histological grade classification (AUC = 0.88). Three model features correlated with clinical outcomes in an independent cohort: granulocyte MAPKAPK2 signaling at the tumor front, stromal CD4+ memory T cell size, and the distance of fibroblasts from the tumor border. This study establishes a robust modeling framework for distilling complex imaging data, uncovering sentinel characteristics of the OSCC TIME to facilitate prognostic biomarkers discovery for recurrence risk stratification and immunomodulatory therapy development.

Epistaxis After Orthognathic Surgery: Literature Review and Three Case Studies.

Study Design: This is a literature review with 3 case studies. Objective: Intraoperative and postoperative bleeding are the most common complications of orthognathic surgery and have the potential to become life-threatening. The rarity of severe postoperative epistaxis has resulted in limited characterization of these cases in the literature. The purpose of this study is to 1) differentiate various presentations of epistaxis following orthognathic surgery in the literature, 2) identify management approaches, and 3) to synthesize a treatment algorithm to guide future management of postoperative epistaxis. Methods: A literature search of PubMed was conducted and 28 cases from 17 studies were assessed. Results: Bleeding within the first week may indicate isolated epistaxis, often resolved with local tamponade. Half of cases were attributed to pseudoaneurysm rupture (n = 14), with epistaxis onset ranging from postoperative day 6 to week 9. Angiography was used in most cases (n = 17), often as the primary imaging modality (n = 11). Nasal endoscopy is a less invasive and effective alternative to angiography with embolization. Proximal vessel ligation was used in 3 cases but is not preferred because collaterals may reconstitute flow through the defect and cause rebleeding. Repeat maxillary down-fracture with surgical exploration was described in 4 cases. Conclusions: As outlined in our management algorithm, nasal packing and tamponade should be followed by either local electrocautery or vascular imaging. Angiography with embolization is the preferred approach to diagnosis and management, whereas surgical intervention is reserved for cases of embolization failure or unavailability.

A Systematic Review of Mandibular Distraction Osteogenesis Versus Orthodontic Airway Plate for Airway Obstruction Treatment in Pierre Robin Sequence.

OBJECTIVE: Mandibular distraction osteogenesis (MDO) is frequently performed to address airway obstruction in patients with Pierre Robin sequence (PRS), though more recently the technique of orthodontic airway plating (OAP) has gained traction. We aimed to evaluate OAP compared to MDO for airway obstruction in PRS. DESIGN: A systematic literature search across PubMed, Embase, and Google Scholar identified all studies published in English, which involved MDO or any form of OAP as treatments for PRS. All relevant articles were reviewed in detail and reported on, adhering to PRISMA guidelines. MAIN OUTCOME MEASURES: Airway (tracheostomy avoidance, decannulation rate), feeding (full oral feeding tolerance). RESULTS: Literature search identified 970 articles, of which 42 MDO studies and 9 OAP studies met criteria for review. A total of 1159 individuals were treated with MDO, and 322 individuals were treated with OAP. Primary outcomes appear similar for MDO and OAP at face value; however, this must be interpreted with different pretreatment contexts in mind. CONCLUSIONS: Orthodontic airway plating may be considered for airway obstruction in PRS, as some airway-related and feeding-related outcomes appear similar with MDO, per existing evidence in the literature. However, since PRS severity differed between studies, OAP cannot be uniformly considered a replacement for MDO. Further research is required to more comprehensively assess these treatment modalities inclusive of metrics that allow for direct comparison.

Conformity of the Virtual Surgical Plan to the Actual Result Comparing Five Craniofacial Procedure Types.

BACKGROUND: The "accuracy" of virtual surgical planning across multiple procedure types is not known. The authors aimed to compare the planned outcome from virtual surgical planning to the actual postoperative outcome for five craniofacial procedure types performed by a single surgeon: implant cranioplasty, cranial vault remodeling, orthognathic surgery, mandible reconstruction, and mandibular distraction. METHODS: Stereolithography formats were obtained from virtual surgical planning and compared to postoperative computed tomographic scans for consecutive patients who underwent one of the five procedure types. Volumetric renderings of the operated bony region of interest were overlaid and compared using a Boolean operation to compute conformity (as a percentage of the region of interest). Conformity across procedure type was analyzed using analysis of variance and post hoc Bonferroni analysis, where appropriate. RESULTS: One hundred thirty patients were included (51.5 percent male and 49.5 percent female; mean age, 27 years; 59 orthognathic surgery, 32 cranial vault remodeling, 16 mandible reconstruction, 12 mandibular distraction, and 11 implant cranioplasty patients). The highest tier of conformity was obtained for implant cranioplasty (median, 76.8 ± 10.3 percent) and mandible reconstruction (mean, 69.4 ± 11.2 percent), followed by orthognathic surgery (mean, 55.0 ± 7.3 percent) and mandibular distraction (median, 41.9 ± 20.3 percent), followed by cranial vault remodeling (mean, 22.2 ± 12.1 percent) (p < 0.001 between tiers and p > 0.05 among tiers). CONCLUSIONS: Virtual surgical planning resulting in custom permanent implants and intraoperative guides provides more predictable results compared to virtual surgical planning used for procedures involving higher degrees of skeletal repositioning and postoperative movement (i.e., mandibular distraction and nonrigid cranial vault remodeling). In cases with expectedly lower conformity, excellent outcomes can be achieved with sound intraoperative judgment.

Facial Asymmetry in Unilateral Condylar Hyperplasia: Comparing Treatment for Active versus Burnt-Out Disease.

BACKGROUND: Facial asymmetry caused by unilateral condylar hyperplasia requires treatment to address facial and occlusal imbalances. There is no definitive evidence to suggest that a single intervention strategy (during either active condylar overgrowth or the burnt-out phase) results in better/more symmetric correction. This study sought to quantify preoperative and postoperative facial asymmetry in unilateral condylar hyperplasia patients comparing treatment for active versus burnt-out disease. METHODS: Preoperative and postoperative three-dimensional photographs were obtained. Images were compared to those of unaffected controls as a standard for normal facial symmetry. Facial asymmetry was assessed using root-mean-square deviation. Paired t tests were performed to compare the root-mean-square deviations of preoperative and postoperative images between the unilateral condylar hyperplasia groups and against controls. RESULTS: Forty patients were included (11 active, nine burnt-out, and 20 controls) and 60 three-dimensional images were evaluated. Preoperatively, patients in the burnt-out group had worse asymmetry than those with active unilateral condylar hyperplasia (p = 0.011). Both groups demonstrated significantly improved symmetry postoperatively (active, p = 0.0069; burnt-out, p = 1.74E-4). However, burnt-out patients remained with some residual asymmetry (p = 4.75E-4), whereas their active counterparts showed no significant difference compared to unaffected controls (p = 0.089). CONCLUSIONS: Patients with end-stage unilateral condylar hyperplasia have more severe facial asymmetry that is more difficult to normalize compared to earlier intervention during active unilateral condylar hyperplasia. These findings suggest that, if possible, corrective intervention is preferable during active unilateral condylar hyperplasia. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Rhinoplasty Using Three-Dimensional Analysis and Simulation.

Treatment of nasal deformity and obstruction requires analysis, planning, and precise execution of rhinoplasty techniques. When performed well, rhinoplasty is a powerful tool for achieving appealing nasal morphology and optimizing function. This article aims to highlight an open approach to septorhinoplasty using a number of techniques that are preferred by the senior author (D.M.S.) to successfully correct a congenital nasal deformity and deviated septum.

Concurrent Platysmaplasty and Genioplasty Using a Novel Intraoral Approach.

Facial aging patients frequently seek improved neck and jawline definition. Microgenia, or lack of chin support, is often overlooked or underdiagnosed in these patients. The authors propose a simultaneous genioplasty, in addition to platysmaplasty and face/neck lift, to address both soft-tissue and bony components, and enhance the cervicomental area. The platysmaplasty is performed in a novel fashion using the intraoral genioplasty incision. The operative sequence includes intraoral incision, platysmal exposure, fat excision, platysmal tightening, genioplasty osteotomy/fixation, and external skin redraping (face/neck lift). Case examples are shown to illustrate appropriate candidate selection and results. Parameters for success include increased chin-throat distance and definition, improved cervicomental angle, and soft-tissue rejuvenation. The novel approach the authors describe enables discrete access to the platysmal and submental region and provides bony definition to help optimize the soft-tissue drape and definition. CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, V.

Management of Unstable Distal Radius Fractures: A Survey of Hand Surgeons.

Background Length of immobilization after operative fixation of unstable distal radius fractures and management in elderly patients is an area of debate. Purpose The purpose of this study is to delineate common practices of fellowship-trained hand surgeons and how they compare with current evidence-based protocols. Methods Surveys were distributed to American Society for Surgery of the Hand members on preferred methods of fixation, postoperative immobilization, and variations in treatment of elderly patients with unstable distal radius fractures. Responses were analyzed in comparison to a literature review. Subgroups were compared with regard to training, practice type, and years in practice. Results Four-hundred eighty-five surveys were analyzed. Volar fixed-angle plating was the most common choice of fixation (84.7%). Patients are most often immobilized for 1 to 2 weeks (40.0%) with range of motion (ROM) therapy begun most commonly between 1 and 4 weeks (47.2%). The majority of surgeons do not treat fractures differently in patients more than 65 years old. Physicians with more than 20 years of experience were significantly more likely to begin wrist ROM sooner with volar plating versus other fixation techniques compared with physicians with less than 20 years of experience (40.7% vs. 34.2%, respectively). Also, physicians in academic-only practices were more likely to immobilize patients for a shorter time after volar plating compared with those in privademics. Conclusion Volar fixed-angle plating is the dominant fixation method for unstable distal radius fractures among fellowship-trained hand surgeons. Elderly patients are not treated more conservatively and rigid immobilization after operative fixation remains the treatment of choice despite current evidence-based protocols.

Concurrent High Condylectomy and Orthognathic Surgery to Address Mandibular and Facial Asymmetry.

Correction of facial asymmetry caused by active unilateral condylar hyperplasia (CH) requires proper diagnosis, arrested ongoing condylar growth, and ultimately orthognathic surgery. Traditionally, prior to performing orthognathic surgery, active CH is addressed either by: awaiting natural cessation of condylar overgrowth, or performing an interval high condylectomy (to stop growth). However, these strategies both add to the total treatment time, by either waiting and confirming no active growth, or performing a first stage growth-arresting procedure. In this report, the authors describe concurrent high condylectomy, and 3-jaw orthognathic surgery, to address the root of the problem and provide aesthetic correction in the same setting. This clinical series illustrates a detailed description of this approach, highlighting operative order, and an analysis of outcomes.

Comparing Outcomes in Orthognathic Surgery Using Clear Aligners Versus Conventional Fixed Appliances.

PURPOSE: Orthognathic surgery for dentofacial deformities is typically preceded and followed by orthodontic treatment. Traditionally, orthodontic hardware is secured to the dentition to allow dental movement and stabilization. Clear-aligner therapy (eg, Invisalign) provides an aesthetic alternative, consisting of a series of transparent trays. Its use has not been described in complex triple-jaw orthognathic surgery. The purpose of this study is to evaluate perioperative outcomes and 3-dimensionally quantify postoperative edema in Invisalign patients undergoing triple-jaw orthognathic procedures, comparing this to patients treated with conventional fixed appliances. The surgical approach to patients with clear-aligners is also outlined. METHODS: The authors conducted a retrospective chart review and 3-dimensional morphometric study of Invisalign patients undergoing triple-jaw surgery (LeFort I osteotomy, bilateral sagittal split osteotomy, and genioplasty). An identical assessment of demographically matched patients treated with conventional fixed appliances was performed and compared with the Invisalign group. RESULTS: Thirty-three patients, with a mean age of 19.99 years, were included: 13 with Invisalign and 20 with conventional fixed appliances. No significant difference was observed in operating time, concurrent extraction of teeth, fat grafting, duration of hospital stay, diet advancement, and use of narcotic analgesics between the 2 groups. Nine patients had sufficient 3-dimensional images for volumetric analysis (4 with Invisalign and 5 with conventional fixed appliances). Postoperative edema was not significantly different (P = 0.712) when comparing conventional fixed appliances (44.29 ±â€Š23.16 cm) to Invisalign (37.36 ±â€Š31.19 cm). CONCLUSION: The present study demonstrates that complex multiple-jaw orthognathic procedures can be successfully performed in Invisalign patients. Perioperative and short-term clinical outcomes are not compromised.

Facial dysmorphology and odontogenic tumor development associated with inborn errors of metabolism: a case report.

PURPOSE: Inborn errors of metabolism (IEMs) are genetic disorders that alter normal physiologic functioning. Deficiency of 3-methylcrotonyl-coenzyme A carboxylase is one such IEM that can lead to major episodes of metabolic dysfunction. Certain IEMs are associated with characteristic congenital dysmorphic facial features. This can be problematic, because these dysmorphisms can mask underlying tumor growth. Literature is lacking on a causal relation between IEM and odontogenic tumor development. MATERIALS AND METHODS: This case was explained in detail and a review of the literature was undertaken. PubMed was used to search for articles involving surgical management of odontogenic myxoma (OM) and associations between odontogenic tumors and IEM. RESULTS: It was determined that the development of odontogenic tumors, specifically OM, is associated with IEMs. These tumors can easily be overlooked as a common dysmorphic feature of an IEM. CONCLUSION: IEMs lead to major metabolic disturbances and, thus, can alter the cellular microenvironment. Hypothetically, these alterations can lead to the development of odontogenic tumors. With the diagnosis of IEM becoming more common owing to improved newborn screening, careful attention should be given to these patients because of the possibility that dysmorphologic facial features could be masking underlying tumor growth.

Takotsubo cardiomyopathy precipitated by maxillofacial surgery and general anesthesia: a case report and review of literature.

PURPOSE: Takotsubo cardiomyopathy (TCM) is a syndrome characterized by a transient episode of heart failure. The specific etiology of this condition is widely speculated. The purpose of this case report and literature review was to investigate the incidence of TCM with regard to general anesthesia, especially those cases involving operative procedures within the realm of oral and maxillofacial surgery. It is intended that the present case serve as a guide for fellow surgeons to identify and manage this syndrome. MATERIALS AND METHODS: The present case was explained and a review of the literature was performed. PubMed was used to search for articles involving surgical procedures under general anesthesia, including oral and maxillofacial surgery. RESULTS: It was determined that TCM rarely occurs in conjunction with surgical procedures under general anesthesia, especially those of the head and neck region. CONCLUSIONS: TCM is an uncommon medical condition with significant morbidity and mortality when managed incorrectly. The occurrence of this syndrome in relation to oral and maxillofacial procedures is also rare, although it is imperative that surgeons be able to recognize and treat this condition appropriately.

Mutational analyses of the BRAF, KRAS, and PIK3CA genes in oral squamous cell carcinoma.

OBJECTIVES: The development of oral squamous cell carcinoma (OSCC) is a complex, multistep process. To date, numerous oncogenes and tumor-suppressor genes have been implicated in oral carcinogenesis. Of particular interest in this regard are genes involved in cell cycling and apoptosis, such BRAF, KRAS, and PIK3CA genes. STUDY DESIGN: Mutations of BRAF, KRAS, and PIK3CA were evaluated by direct genomic sequencing of exons 1 of KRAS, 11 and 15 of BRAF, and 9 and 20 of PIK3CA in OSCC specimens. RESULTS: Both BRAF and KRAS mutations were detected with a mutation frequency of 2% (1/42). PIK3CA mutations were detected at 3% (1/35). CONCLUSIONS: This is the first report implicating BRAF mutation in OSCC. Our study supports that mutations in the BRAF, KRAS, and PIK3CA genes make at least a minor contribution to OSCC tumorigenesis, and pathway-specific therapies targeting these 2 pathways should be considered for OSCC in a subset of patients with these mutations.

Preferred treatment methods for primary tooth vital pulpotomies. A survey.

This investigation evaluated preferred treatment methods for primary tooth vital pulpotomies. One hundred and thirty surveys were sent to a randomly selected sample of board-certified pediatric dentists practicing in the United States. Ninety-two questionnaires were returned, for a 71% response rate. This yielded a sample group of 92 board-certified pediatric dentists. The most commonly used medicament was formocresol. Seventy-three percent using formocresol said they were not concerned about adverse side effects of formocresol and formaldehyde. Sixty-one percent of respondents used formocresol for primary tooth vital pulpotomies. Twenty-eight percent of respondents used undiluted, and 33% used diluted. The results of this survey suggest that the majority of dentists who used formocresol were not concerned with any adverse effects.

BRAF and KRAS gene mutations in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) of the pancreas.

The Raf/MEK/ERK (MAPK) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Our study was performed to elucidate a possible role of BRAF in the development of IPMN (Intraductal Papillary Mucinous Neoplasm) and IPMC (Intraductal Papillary Mucinous Carcinoma) of the pancreas. Mutations of BRAF and KRAS were evaluated in 36 IPMN/IPMC samples and two mucinous cystadenomas by direct genomic sequencing. Exons 1 for KRAS, and 5, 11, and 15 for BRAF were examined. Totally we identified 17 (47%) KRAS mutations in exon 1, codon 12 and one missense mutation (2.7%) within exon 15 of BRAF. The mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. Our data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.