Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

Unipolar myomectomy for congenital muscular torticollis: A retrospective study.

In this study, unipolar myomectomy was used to address limited neck movement and tight muscles in pediatric, adolescent, and adult patients. A retrospective chart review was performed for patients from January 2006 to February 2023, who were diagnosed with congenital muscular torticollis and underwent a unipolar myomectomy. Outcome evaluation, adapted from the Cheng and Tang system - cervicomandibular angle (CMA), facial asymmetry, cranial asymmetry, tilting limitation (TL), rotation limitation (RL), subjective assessment, and residual contracture - included various parameters scored from 0 to 3 points and categorized as poor, fair, good, or excellent. In total, the data for 36 patients (21 males and 15 females) were analyzed. Participants were aged 0.8-38 years. Surgery improved CMA, RL, and TL, with no complications (12.2°-1.2°, 18.6°-5.2°, and 17.6°-6.5° for CMA, RL, and TL, respectively; p < 0.001). The mean overall score was comparable among different age groups (2.8 ± 0.5, 2.2 ± 0.62, and 2.1 ± 0.37 for the pediatric, adolescent, and adult groups, respectively). Within the limitations of the study it seems that unipolar myomectomy is a promising, effective surgical option for individuals of multiple age groups.

Speech Outcomes in 5-Year-Old Korean Children with Bilateral Cleft Lip and Palate.

Background Among the cleft types, bilateral cleft lip and palate (BCLP) generally requires multiple surgical procedures and extended speech therapy to achieve normal speech development. This study aimed to describe speech outcomes in 5-year-old Korean children with BCLP and examine whether normal speech could be achieved before starting school. Methods The retrospective study analyzed 52 children with complete BCLP who underwent primary palatal surgery at a tertiary medical center. Three speech-language pathologists made perceptual judgments on recordings from a speech follow-up assessment of 5-year-old children. They assessed the children's speech in terms of articulation, speech intelligibility, resonance, and voice using the Cleft Audit Protocol for Speech-Augmented-Korean Modification. Results The results indicated that at the age of five, 65 to 70% of children with BCLP presented articulation and resonance within normal or acceptable ranges. Further, seven children with BCLP (13.5%) needed both additional speech therapy and palatal surgery for persistent velopharyngeal insufficiency and speech problems even at the age of five. Conclusion This study confirmed that routine follow-up speech assessments are essential as a substantial number of children with BCLP require secondary surgical procedures and extended speech therapy to achieve normal speech development.

Facial palsy reconstruction.

The facial nerve stimulates the muscles of facial expression and the parasympathetic nerves of the face. Consequently, facial nerve paralysis can lead to facial asymmetry, deformation, and functional impairment. Facial nerve palsy is most commonly idiopathic, as with Bell palsy, but it can also result from a tumor or trauma. In this article, we discuss traumatic facial nerve injury. To identify the cause of the injury, it is important to first determine its location. The location and extent of the damage inform the treatment method, with options including primary repair, nerve graft, cross-face nerve graft, nerve crossover, and muscle transfer. Intracranial proximal facial nerve injuries present a challenge to surgical approaches due to the complexity of the temporal bone. Surgical intervention in these cases requires a collaborative approach between neurosurgery and otolaryngology, and nerve repair or grafting is difficult. This article describes the treatment of peripheral facial nerve injury. Primary repair generally offers the best prognosis. If primary repair is not feasible within 6 months of injury, nerve grafting should be attempted, and if more than 12 months have elapsed, functional muscle transfer should be performed. If the affected nerve cannot be utilized at that time, the contralateral facial nerve, ipsilateral masseter nerve, or hypoglossal nerve can serve as the donor nerve. Other accompanying symptoms, such as lagophthalmos or midface ptosis, must also be considered for the successful treatment of facial nerve injury.

A Grading System-Guided Approach to the Severely Contracted Nose.

PURPOSE: Capsular contracture is a rare but serious complication of silicone implant-based augmentation rhinoplasty. When severe, the contracture can affect all layers of the nose, causing significant scarring and disfigurement. There is currently no standardized method of evaluating contracted noses and a paucity of literature on the treatment of severe contracture. Therefore, this study aimed to establish a comprehensive grading system and treatment approach for patients with nasal contracture secondary to silicone implant-based rhinoplasty. METHODS: We conducted a retrospective analysis on patients who presented with nasal contracture from 2012 to 2021. All preoperative photographs were evaluated by two plastic surgeons, twice at 1-month intervals. The proposed grading system comprised: normal (grade I), mild contracture with detectable implant (grade II), moderate contracture with skin thinning (grade III), severe contracture with short nose deformity (grade IV), and destructive contracture with scarring of the dorsal skin (grade Va), or columella deficiency (grade Vb). Inter- and intraobserver agreement was assessed using the kappa value to determine the reliability of the system. RESULTS: Based on 87 patients, interobserver agreement was substantial for both evaluation time points (k = 0.701 and 0.723). Intraobserver agreement was excellent for evaluator 1 (k = 0.822) and substantial for evaluator 2 (k = 0.699). CONCLUSIONS: Using this grading system, we propose a graduated treatment algorithm for contracted noses. Most notable is our use of radial forearm free or forehead flaps to reconstruct the columella in grade Vb patients. By combining reconstructive and aesthetic principles, this treatment approach provides an effective and elegant solution for the management of the severely contracted nose. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Functional outcomes and recurrence determinants in craniofacial fibrous dysplasia: Insights from 3D computed tomography and comprehensive clinical evaluation.

BACKGROUND: This study aimed to identify risk factors for postoperative lesion regrowth and to assess functional outcomes in craniofacial fibrous dysplasia, using a three-dimensional computed tomographic volumetric analysis. METHODS: A retrospective analysis was conducted on 47 patients with craniofacial fibrous dysplasia who were treated from July 2005 to December 2020. Patients were treated with either conservative shaving or radical excision followed by reconstruction. Demographic data, surgical details, lesion recurrence, and functional outcomes were assessed. Lesion volume changes and recurrence were evaluated clinically and through a computed tomographic volumetric analysis. RESULTS: Among the patients, 16 underwent conservative treatment, whereas 31 received radical treatment. The radical group showed more significant improvements in functional outcomes, particularly in orbital dystopia and facial asymmetry. Postoperative lesion volume was notably lower in the radical group (41.94 ± 38.13 cm3) compared with the conservative group (78.3 ± 47.3 cm3, p = 0.008). This reduction was maintained over an average follow-up of 3 years. Lesion growth rates were similar between the groups (8.17 ± 5.85% in radical vs. 5.84 ± 6.43% in conservative, p = 0.268). Multivariate analysis indicated that patients aged ≤20 years and those with multifocal involvement had significantly higher risks of recurrence, with adjusted odds ratios of 11.269 (p = 0.039) and 6.914 (p = 0.046), respectively. CONCLUSIONS: Our findings suggest that both conservative and radical treatments for craniofacial fibrous dysplasia provide benefits, with the radical approach notably enhancing functional outcomes. However, neither method definitively reduces lesion recurrence, highlighting the necessity for an individualized treatment strategy. This approach should balance functional enhancement with recurrence risks, tailored to each patient's specific clinical scenario.

Blood Lymphocytes as a Prognostic Factor for Stage III Non-Small Cell Lung Cancer with Concurrent Chemoradiation.

We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

Biomarker Analysis from a Phase I/Ib Study of Regorafenib and Nivolumab in Mismatch Repair-Proficient Advanced Refractory Colorectal Cancer.

Previously, we reported the modest but durable anticancer activity of regorafenib/nivolumab in mismatch repair-proficient (pMMR) refractory colorectal cancer in our I/Ib study. Our finding suggests the necessity of biomarkers for better selection of patients. Baseline clinical and pathological characteristics, blood and tumor samples from the patients in the trial were collected and evaluated to discover potential biomarkers. The obtained samples were assessed for immunohistochemistry, ELISA and RNA sequencing. Their correlations with clinical outcome were analyzed. A high albumin level was significantly associated with improved progression-free survival (PFS), overall survival (OS) and disease control. Non-liver metastatic disease showed prolonged PFS and OS. Low regulatory T-cell (Treg) infiltration correlated with prolonged PFS. Low MIP-1ß was associated with durable response and improved OS significantly. Upregulation of 23 genes, including CAPN9, NAPSA and ROS1, was observed in the durable disease control group, and upregulation of 10 genes, including MRPS18A, MAIP1 and CMTR2, was associated with a statistically significant improvement of PFS. This study suggests that pretreatment albumin, MIP-1ß, non-liver metastatic disease and Treg infiltration may be potential predictive biomarkers of regorafenib/nivolumab in pMMR colorectal cancer. Further studies are needed to confirm these findings.

Application of augmented reality using automatic markerless registration for facial plastic and reconstructive surgery.

This study aimed to present a novel markerless augmented reality (AR) system using automatic registration based on machine-learning algorithms that visualize the facial region and provide an intraoperative guide for facial plastic and reconstructive surgeries. This study prospectively enrolled 20 patients scheduled for facial plastic and reconstructive surgeries. The AR system visualizes computed tomographic data in three-dimensional (3D) space by aligning with the point clouds captured by a 3D camera. Point cloud registration consists of two stages: the preliminary registration gives an initial estimate of the transformation using landmark detection, followed by the precise registration using Iterative Closest Point algorithms. Computed Tomography (CT) data can be visualized as two-dimensional slice images or 3D images by the AR system. The AR registration error was defined as the cloud-to-cloud distance between the surface data obtained from the CT and 3D camera. The error was calculated in each facial territory, including the upper, middle, and lower face, while patients were awake and orally intubated, respectively. The mean registration errors were 1.490 ± 0.384 mm and 1.948 ± 0.638 mm while patients were awake and orally intubated, respectively. There was a significant difference in the errors in the lower face between patients while they were awake (1.502 ± 0.480 mm) and orally intubated (2.325 ± 0.971 mm) when stratified by facial territories (p = 0.006). The markerless AR can accurately visualize the facial region with a mean overall registration error of 1-2 mm, with a slight increase in the lower face due to errors arising from tube intubation.

Hemi one-piece distraction osteogenesis for unilateral coronal craniosynostosis.

INTRODUCTION: It was the aim of the study to assess the efficacy of the hemi one-piece distraction osteogenesis and to compare it to the traditional one-piece distraction osteogenesis technique. METHODS: Two different surgical techniques were used; the one-piece distraction and the hemi one-piece distraction. The principal distinction between the two techniques is that in the hemi style approach, the intact sutures on the contralateral side were left undisturbed, with no osteotomy performed. RESULTS: The hemi one-piece group had a significantly lower median value of plastic surgery time, total operation time, and transfusion rate (plastic surgery time 69 min (range 65-120) vs. 20 min (range 17-32.5), p < 0.001; transfusion 80 mL (range 0-150) vs. 0 mL (0-60), p = 0.1. Nasofrontal advancement was successful with no major complications. Median endocranial angulation improved (one-piece: 166.1°-176.0°, hemi: 162.9°-173.0°, p = 0.023 & p = 0.012 respectively). CONCLUSION: This study reveals less invasive, highly effective techniques for craniosynostosis treatment, notably a unilateral osteotomy with distraction method. Nevertheless, to confirm their long-term efficacy and durability, more studies with longer follow-ups are essential.

SGLT2 inhibitor dapagliflozin protects the kidney in a murine model of Balkan nephropathy.

Proximal tubular uptake of aristolochic acid (AA) forms aristolactam (AL)-DNA adducts, which cause a p53/p21-mediated DNA damage response and acute tubular injury. Recurrent AA exposure causes kidney function loss and fibrosis in humans (Balkan endemic nephropathy) and mice and is a model of (acute kidney injury) AKI to chronic kidney disease (CKD) transition. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. C57BL/6J mice (15-wk-old) were administered vehicle or AA every 3 days for 3 wk (10 and 3 mg/kg ip in females and males, respectively). Dapagliflozin (dapa, 0.01 g/kg diet) or vehicle was initiated 7 days prior to AA injections. All dapa effects were sex independent, including a robust glycosuria. Dapa lowered urinary kidney-injury molecule 1 (KIM-1) and albumin (both normalized to creatinine) after the last AA injection and kidney mRNA expression of early DNA damage response markers (p53 and p21) 3 wk later at the study end. Dapa also attenuated AA-induced increases in plasma creatinine as well as AA-induced up-regulation of renal pro-senescence, pro-inflammatory and pro-fibrotic genes, and kidney collagen staining. When assessed 1 day after a single AA injection, dapa pretreatment attenuated AL-DNA adduct formation by 10 and 20% in kidney and liver, respectively, associated with reduced p21 expression. Initiating dapa application after the last AA injection also improved kidney outcome but in a less robust manner. In conclusion, the first evidence is presented that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.NEW & NOTEWORTHY Recurrent exposure to aristolochic acid (AA) causes kidney function loss and fibrosis in mice and in humans, e.g., in the form of the endemic Balkan nephropathy. Inhibitors of the proximal tubule sodium-glucose transporter SGLT2 can protect against CKD progression, but their effect on AA-induced kidney injury remains unknown. Here we provide the first evidence in a murine model that pretreatment with an SGLT2 inhibitor can attenuate the AA-induced DNA damage response and subsequent nephropathy.

Efficacy and feasibility of a forehead flap surgical guide for nasal reconstruction.

For successful nasal reconstruction using a forehead flap, three-dimensional (3D) nasal defects need to be translated into a two-dimensional (2D) forehead surface. For this study, a patient-specific 3D-printed forehead flap guide that could precisely translate a virtually simulated nasal shape into a 2D flap template was developed. The study aimed to evaluate the feasibility and efficacy of a 3D-printed forehead flap guide for nasal reconstructions. The 3D nasal surface was scanned using a 3D camera, and a 'digital clay' process was performed to correct the nasal deformity. The 3D morphology was flattened into a 2D forehead flap guide. The guide was 3D-printed and used for the forehead flap design. Photographic records were used to conduct anthropometric and aesthetic evaluations. Between October 2016 and August 2020, forehead flaps were performed using the forehead flap guide (guide group) and traditional templating method (control group) in 16 and 15 patients, respectively. The alar shape was more symmetric in the guide group than in the control group, with smaller right-to-left differences in alar width (p = 0.01) and height (p = 0.05). Regarding aesthetic evaluations, nose contour (p = 0.02) and nasal symmetry (p = 0.033) were better in the guide group than in the control group. The mean operative time was significantly shorter (91.9 ± 10.7 min) in the guide group than in the control group (116.4 ± 13.6 min) (p = 0.001). Our findings suggest that a 3D-printed forehead flap surgical guide can be effectively used in nasal reconstruction to reduce operative time and improve aesthetic outcomes.

Real-world first-line afatinib for advanced EGFR mutation-positive non-small cell lung cancer in Korea: updated survival data.

Background: Data from clinical trials and real-world studies show that afatinib is effective in treating non-small cell lung cancer (NSCLC) harboring activating mutations in the epidermal growth factor receptor (EGFR) gene. A previous analysis of patients enrolled in the Korean Academy of Tuberculosis and Respiratory Disease (KATRD) EGFR cohort showed that first-line afatinib was well tolerated and effectiveness results were encouraging. At the time of the previous analysis, survival data were not mature. Here we briefly present updated survival data from the cohort. Methods: The study was a retrospective, multicenter (15 sites) review of electronic records of Korean adult patients (aged >20 years) with advanced EGFR mutation-positive NSCLC who initiated first-line afatinib (N=421). Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier survival curves. Results: Overall, median PFS was 20.2 months and median OS was 48.6 months. OS rates at 36 and 60 months were 60.1% and 42.3%, respectively. Presence vs. absence of baseline brain metastases was associated with significantly reduced median PFS (14.9 vs. 28.0 months; P<0.001) and median OS (32.2 vs. 65.6 months; P<0.001). The presence of common baseline EGFR mutations (Del19, L858R) was associated with significantly prolonged median OS (49.6 vs. 30.1 months; P=0.017). In patients stratified by the presence/absence of T790M EGFR mutation, the T790M mutation was associated with significantly reduced median PFS (P=0.0005) but there was no significant difference between groups in survival (P=0.263). There were no significant differences in PFS or OS for patients stratified by afatinib dose reduction or by age group (<70 vs. ≥70 years). Conclusions: Afatinib was effective in Korean patients with EGFR mutation-positive NSCLC with median OS over 4 years. The presence of baseline brain metastases and/or uncommon EGFR mutations were associated with reduced survival. In the absence of baseline brain metastases, median OS was more than 5 years.

Genetic Alterations and Risk Factors for Recurrence in Patients with Non-Small Cell Lung Cancer Who Underwent Complete Surgical Resection.

A definitive surgical resection is the preferred treatment for early-stage non-small cell lung cancer (NSCLC). Research on genetic alterations, including epidermal growth factor receptor (EGFR) mutations, in early-stage NSCLC remains insufficient. We investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutations and recurrence after a complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resections at a single regional cancer center in Korea were recruited. We retrospectively compared the clinical and pathological data between the recurrence and non-recurrence groups. Among the 659 enrolled cases, the median age was 65.86 years old and the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutations was 43% (194/451). Among them, L858R point mutations and exon 19 deletions were 52.3% and 42%, respectively. Anaplastic lymphoma kinase (ALK) rearrangement was found in 5.7% of patients (26/453) and ROS proto-oncogene 1 (ROS1) fusion was found in 1.6% (7/441). The recurrence rate for the entire population was 19.7%. In the multivariate analysis, the presence of EGFR mutations (hazard ratio (HR): 2.698; 95% CI: 1.458-4.993; p = 0.002), stage II (HR: 2.614; 95% CI: 1.29-5.295; p = 0.008) or III disease (HR: 9.537; 95% CI: 4.825-18.852; p < 0.001) (vs. stage I disease), and the presence of a pathologic solid type (HR: 2.598; 95% CI: 1.405-4.803; p = 0.002) were associated with recurrence. Among the recurrence group, 86.5% of the patients with EGFR mutations experienced distant metastases compared with only 66.7% of the wild type (p = 0.016), with no significant difference in median disease-free survival (52.21 months vs. not reached; p = 0.983). In conclusion, adjuvant or neoadjuvant targeted therapy could be considered more actively because EGFR mutations were identified as an independent risk factor for recurrence and were associated with systemic recurrence. Further studies on perioperative therapy for other genetic alterations are necessary.

Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B.

High-level MET amplification (METamp) is a primary driver in ∼1%-2% of non-small cell lung cancers (NSCLCs). Cohort B of the phase 2 VISION trial evaluates tepotinib, an oral MET inhibitor, in patients with advanced NSCLC with high-level METamp who were enrolled by liquid biopsy. While the study was halted before the enrollment of the planned 60 patients, the results of 24 enrolled patients are presented here. The objective response rate (ORR) is 41.7% (95% confidence interval [CI], 22.1-63.4), and the median duration of response is 14.3 months (95% CI, 2.8-not estimable). In exploratory biomarker analyses, focal METamp, RB1 wild-type, MYC diploidy, low circulating tumor DNA (ctDNA) burden at baseline, and early molecular response are associated with better outcomes. Adverse events include edema (composite term; any grade: 58.3%; grade 3: 12.5%) and constipation (any grade: 41.7%; grade 3: 4.2%). Tepotinib provides antitumor activity in high-level METamp NSCLC (ClinicalTrials.gov: NCT02864992).

Serum KL-6 levels predict the occurrence and severity of treatment-related interstitial lung disease in lung cancer.

In this study, we aimed to investigate the feasibility of serum Krebs von den Lungen-6 (KL-6) as a potential biomarker for treatment-related ILD (TR-ILD) in lung cancer. We recruited patients with lung cancer in whom KL-6 was measured to differentiate between pneumonia and ILD (category 1), diagnose and assess the severity of suspicious ILD (category 2), or evaluate baseline levels before cancer treatment (category 3). Among 1,297 patients who underwent KL-6 testing, 422 had lung cancer, and TR-ILD was detected in 195 patients. In categories 1-2, median KL-6 level was higher in drug-induced ILD or acute exacerbation of underlying ILD than in no ILD or radiation-induced pneumonitis, and it was correlated with the severity of TR-ILD. High KL-6 level (cut-off: > 436U/mL) was an independent risk factor for severe TR-ILD, and low KL-6 level with high procalcitonin level (> 0.5 ng/mL) could exclude severe TR-ILD. Patients with severe TR-ILD had worse overall survival than those without, whereas high baseline KL-6 level was associated with worse survival, especially in patients without severe TR-ILD. Therefore, serum KL-6 may be a surrogate marker for predicting the occurrence and assessing the severity of TR-ILD at the time of suspected ILD and before lung cancer treatment.

"Gearing Effect in Clockwise Rotational Orthognathic Surgery".

BACKGROUND: The standard procedure for the management of skeletal class III malocclusion is maxillary advancement with mandibular setback. Occlusal plane altering orthognathic surgery, such as jaw rotation, is useful as well. Although clockwise jaw rotation is a common procedure, its mechanism has not been well-investigated. Therefore, in this study, we aim to introduce the gearing effect to correct class III malocclusion in Asians by maxillary posterior impaction via clockwise rotation without advancing the maxilla. METHODS: Patients with class III correction with clockwise rotation of the maxillomandibular complex without maxillary advancement were included, while those with genioplasty were excluded. Various facial skeletal cephalometric landmarks were measured through artificial intelligence based cephalometric analysis software. The gearing effect was determined by dividing the lower anterior facial height (LAFH) in relatively short and long groups compared to those in the ANS‒PNS length. RESULTS: In a total of 29 patients, the amount of Menton setback between group 1 (n=15, short LAFH) and group 2 (n=14, long LAFH) was 1.67±0.66 and 2.74±0.99 mm per 1 mm of PNS impaction, respectively (p=0.002), and 1.58(interquartile range(IQR) 0.78) and 1.95(IQR 1.05) mm per 1° clockwise rotation of palatal angle, respectively (p=0.007). The convexity of the A point was improved without any significant change in the SNA angle before and after surgery. CONCLUSIONS: This article addressed the scientific evidence in impact of clockwise rotational orthognathic surgery based on the gearing effect. Considering the gearing effect, the mandibular setback turned out to be more effective in patients with a long LAFH.

A Comparative Study of Titanium Cranioplasty for Extensive Calvarial Bone Defects: Three-Dimensionally Printed Titanium Implants Versus Premolded Titanium Mesh.

OBJECTIVE: This study compared the complications and symmetry outcomes between 3-dimensionally printed titanium implants and premolded titanium mesh in patients with extensive calvarial bone defects. METHODS: This retrospective analysis included patients with calvarial defects >50 cm2 undergoing cranioplasty who received either a 3-dimensionally printed titanium implant manufactured by selective laser melting techniques (N = 12) or a premolded titanium mesh customized onto a 3-dimensionally printed skull template (N = 23). Complications including intracranial infection, hardware extrusion, wound dehiscence, and cerebrospinal fluid leaks were investigated. Predictive factors affecting complications were investigated to identify the odds ratios in univariate and multivariate analyses. The symmetry was assessed by calculating the root mean square deviation, which showed the morphological deviation of the selected area compared with the mirrored image of the contralateral region. RESULTS: The overall complication rate was 26.1% (6/23 patients) in the premolded titanium group and 16.7% (2/12 patients) in the 3-dimensionally printed group. The reoperation rates did not differ significantly between the 2 groups (3-dimensionally printed group, 16.7%, versus premolded group, 21.7%). In multivariate analysis, only the number of previous cranial operation was significantly associated with the complication rate (odds ratio, 2.42; 95% confidence interval, 1.037-5.649; P = 0.041). The mean ± SD of the root mean square deviation was significantly smaller in the 3-dimensionally printed group (2.58 ± 0.93 versus 4.82 ± 1.31 mm, P < 0.001). CONCLUSIONS: The 3-dimensionally printed titanium implant manufactured by the selective laser melting technique showed comparable stability and improved symmetry outcomes compared with the conventional titanium mesh in the reconstruction of extensive calvarial defects.

Three-Dimensional Analysis of Flap Volume Change in Total Tongue Reconstruction: Focus on Reinnervated Dynamic Tongue Reconstruction.

In general, flap volume decreases over time and further in the case of a denervated muscle flap. In our institution, dynamic reconstruction, including functional muscle flaps, has been used to aid functional recovery in the past 6 years. This study aimed to determine the effect of volume change of the fat and muscular sections of reconstructed tongue flaps after motor nerve reinnervation in dynamic total tongue reconstruction using 3-dimensional measurement and analysis. A retrospective chart review was performed on 21 patients who underwent total tongue reconstruction using an anterolateral thigh free flap from 2015 to 2020. The fat and muscle volumes of the flap were measured using computed tomography data obtained before surgery (T0), 2 weeks after surgery (T1), and 6 months after surgery (T2) using a 3-dimensional rendering software. Among the 21 patients that underwent tongue reconstruction, 10 underwent dynamic reconstruction, whereas 11 underwent conventional reconstruction using a fasciocutaneous flap. T2 volume compared with T1 was 69.08% in the conventional reconstruction group, and the fat and muscle portions in the dynamic reconstruction group were 77.04% and 69.06%, respectively. No significant difference was noted in the volume change between the 2 groups. After dynamic tongue reconstruction, the muscular volume of the flap had similar volume reduction rate as the fat volume. The dynamic reconstruction was effective not only for functional muscle transfer but also for maintaining the volume of the reconstructed muscle flap.

Differences in the stability of the lesser and greater maxillary segments after cleft orthognathic surgery: A retrospective study using 3D analysis.

The aim of this study was to determine whether significant differences in postoperative stability exist between the lesser and the greater maxillary segments after cleft orthognathic surgery in patients with and without residual alveolar cleft. A retrospective study of orthognathic patients with unilateral cleft was conducted. The patients were divided into two groups according to maxillary status before surgery, with group 1 comprising single-piece maxilla and group 2 comprising two-piece maxilla. Four maxillary points were used for intra- and intergroup comparisons of movements and relapses between the two maxillary segments. In total, 24 patients were included. The intragroup comparison showed significant differences in vertical relapses between lesser and greater segments in both group 1 (anterior, p = 0.004 and posterior, p = 0.01) and group 2 (posterior, p = 0.013). With regard to intergroup comparison, the lesser segments in the two groups differed in transverse movements (anterior, p = 0.048) and relapses (posterior; p = 0.04), while the greater segments differed in transverse movements (anterior, p = 0.014 and posterior, p = 0.019), with significant differences in relapses anteriorly (vertical, p = 0.031 and sagittal, p = 0.036) and posteriorly (transverse, p = 0.022). Maxillary changes following cleft orthognathic surgery showed significant differences between the lesser and the greater segments. These findings imply that 3D images should be used to assess each maxillary segment separately with regard to planning and outcome evaluation.