Atherogenic dyslipidemia promotes autoimmune follicular helper T cell responses via IL-27.

The incidence of atherosclerosis is higher among patients with systemic lupus erythematosus (SLE); however, the mechanism by which an atherogenic environment affects autoimmunity remains unclear. We found that reconstitution of atherosclerosis-prone Apoe-/- and Ldlr-/- mice with bone marrow from lupus-prone BXD2 mice resulted in increased autoantibody production and glomerulonephritis. This enhanced disease was associated with an increase in CXCR3+ follicular helper T cells (TFH cells). TFH cells isolated from Apoe-/- mice had higher expression of genes associated with inflammatory responses and SLE and were more potent in inducing production of the immunoglobulin IgG2c. Mechanistically, the atherogenic environment induced the cytokine IL-27 from dendritic cells in a Toll-like receptor 4 (TLR4)-dependent manner, which in turn triggered the differentiation of CXCR3+ TFH cells while inhibiting the differentiation of follicular regulatory T cells. Blockade of IL-27 signals diminished the increased TFH cell responses in atherogenic mice. Thus, atherogenic dyslipidemia augments autoimmune TFH cell responses and subsequent IgG2c production in a TLR4- and IL-27-dependent manner.

Publisher Correction: Atherogenic dyslipidemia promotes autoimmune follicular helper T cell responses via IL-27.

In the version of this article initially published, the third label along the horizontal axis of Fig. 4b (Il13a) and the middle label above each plot in Fig. 6k (Stat-/-) were incorrect, and the hash marks along the horizontal axis for Fig. 6i were spaced incorrectly. Also, the statistical results in the citation for Supplementary Fig. 5a (*P < 0.05, **P < 0.01 and ***P < 0.001 (unpaired Student's t-test)) in the fifth subsection of Results were incorrect. The correct label for Fig. 4b is Il23a and for Fig. 6k is Stat1-/-, and the right hash mark along the horizontal axis for Fig. 6i should be beneath the data points at right. The correct citation of the statistical results is as follows: "(P < 0.05 and P < 0.01 (unpaired Student's t-test); Supplementary Fig. 5a)." The errors have been corrected in the HTML and PDF version of the article.

Alternative Wnt Signaling Activates YAP/TAZ.

The transcriptional co-activators YAP and TAZ are key regulators of organ size and tissue homeostasis, and their dysregulation contributes to human cancer. Here, we discover YAP/TAZ as bona fide downstream effectors of the alternative Wnt signaling pathway. Wnt5a/b and Wnt3a induce YAP/TAZ activation independent of canonical Wnt/ß-catenin signaling. Mechanistically, we delineate the "alternative Wnt-YAP/TAZ signaling axis" that consists of Wnt-FZD/ROR-Gα12/13-Rho GTPases-Lats1/2 to promote YAP/TAZ activation and TEAD-mediated transcription. YAP/TAZ mediate the biological functions of alternative Wnt signaling, including gene expression, osteogenic differentiation, cell migration, and antagonism of Wnt/ß-catenin signaling. Together, our work establishes YAP/TAZ as critical mediators of alternative Wnt signaling.

Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.

Autophagy is a stress response protecting cells from unfavorable conditions, such as nutrient starvation. The class III phosphatidylinositol-3 kinase, Vps34, forms multiple complexes and regulates both intracellular vesicle trafficking and autophagy induction. Here, we show that AMPK plays a key role in regulating different Vps34 complexes. AMPK inhibits the nonautophagy Vps34 complex by phosphorylating T163/S165 in Vps34 and therefore suppresses overall PI(3)P production and protects cells from starvation. In parallel, AMPK activates the proautophagy Vps34 complex by phosphorylating S91/S94 in Beclin1 to induce autophagy. Atg14L, an autophagy-essential gene present only in the proautophagy Vps34 complex, inhibits Vps34 phosphorylation but increases Beclin1 phosphorylation by AMPK. As such, Atg14L dictates the differential regulation (either inhibition or activation) of different Vps34 complexes in response to glucose starvation. Our study reveals an intricate molecular regulation of Vps34 complexes by AMPK in nutrient stress response and autophagy.

Predicting Lung Cancer in Korean Never-Smokers With Polygenic Risk Scores.

In the last few decades, genome-wide association studies (GWAS) with more than 10,000 subjects have identified several loci associated with lung cancer and these loci have been used to develop novel risk prediction tools for cancer. The present study aimed to establish a lung cancer prediction model for Korean never-smokers using polygenic risk scores (PRSs); PRSs were calculated using a pruning-thresholding-based approach based on 11 genome-wide significant single nucleotide polymorphisms (SNPs). Overall, the odds ratios tended to increase as PRSs were larger, with the odds ratio of the top 5% PRSs being 1.71 (95% confidence interval: 1.31-2.23) using the 40%-60% percentile group as the reference, and the area under the curve (AUC) of the prediction model being of 0.76 (95% confidence interval: 0.747-0.774). The receiver operating characteristic (ROC) curves of the prediction model with and without PRSs as covariates were compared using DeLong's test, and a significant difference was observed. Our results suggest that PRSs can be valuable tools for predicting the risk of lung cancer.

Metabolic Communication by SGLT2 Inhibition.

BACKGROUND: SGLT2 (sodium-glucose cotransporter 2) inhibitors (SGLT2i) can protect the kidneys and heart, but the underlying mechanism remains poorly understood. METHODS: To gain insights on primary effects of SGLT2i that are not confounded by pathophysiologic processes or are secondary to improvement by SGLT2i, we performed an in-depth proteomics, phosphoproteomics, and metabolomics analysis by integrating signatures from multiple metabolic organs and body fluids after 1 week of SGLT2i treatment of nondiabetic as well as diabetic mice with early and uncomplicated hyperglycemia. RESULTS: Kidneys of nondiabetic mice reacted most strongly to SGLT2i in terms of proteomic reconfiguration, including evidence for less early proximal tubule glucotoxicity and a broad downregulation of the apical uptake transport machinery (including sodium, glucose, urate, purine bases, and amino acids), supported by mouse and human SGLT2 interactome studies. SGLT2i affected heart and liver signaling, but more reactive organs included the white adipose tissue, showing more lipolysis, and, particularly, the gut microbiome, with a lower relative abundance of bacteria taxa capable of fermenting phenylalanine and tryptophan to cardiovascular uremic toxins, resulting in lower plasma levels of these compounds (including p-cresol sulfate). SGLT2i was detectable in murine stool samples and its addition to human stool microbiota fermentation recapitulated some murine microbiome findings, suggesting direct inhibition of fermentation of aromatic amino acids and tryptophan. In mice lacking SGLT2 and in patients with decompensated heart failure or diabetes, the SGLT2i likewise reduced circulating p-cresol sulfate, and p-cresol impaired contractility and rhythm in human induced pluripotent stem cell-derived engineered heart tissue. CONCLUSIONS: SGLT2i reduced microbiome formation of uremic toxins such as p-cresol sulfate and thereby their body exposure and need for renal detoxification, which, combined with direct kidney effects of SGLT2i, including less proximal tubule glucotoxicity and a broad downregulation of apical transporters (including sodium, amino acid, and urate uptake), provides a metabolic foundation for kidney and cardiovascular protection.

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.

Enhancing Surgical Approach: Breakthrough Markerless Surface Registration With Augmented Reality for Zygomatic Complex Fracture Surgeries.

BACKGROUND: Innovative technologies with surgical navigation have been used for enhancing surgical accuracies for zygomaticomaxillary complex (ZMC) fractures and offers advantages in precision, accuracy, effectiveness, predictability, and symmetry improvement. Moreover, augmented reality (AR) navigation technology combines virtual reality, 3-dimensional (3D) reconstruction, and real-time interaction, making it ideal for bone tissue operations. Our study explored the usefulness and clinical efficacy of AR technology in intraoperative guidance for reducing ZMC fractures. METHODS: We retrospectively studied 35 patients with zygomatic complex fractures, comparing outcomes of AR-guided and conventional methods. Furthermore, the AR system provided real-time visualization and guidance. The evaluation included reduction accuracy using root mean square (RMS) value and symmetry analysis using a mirror image of 3D models. Results demonstrated the feasibility and effectiveness of the AR-guided method in improving outcomes and patient satisfaction. RESULTS: In 35 patients (25 males, 10 females), AR-guided (n = 19) and conventional (n = 16) approaches were compared. Age, sex, and fracture type exhibited no significant differences between groups. No complications occurred, and postoperative RMS error significantly decreased ( P < 0.001). The AR group had a lower postoperative RMS error ( P = 0.034). CONCLUSIONS: Augmented reality-guided surgery improved accuracy and outcomes in zygomatic complex fractures. Real-time visualization enhanced precision during reduction and fixation. This innovative approach promises enhanced surgical accuracy and patient outcomes in craniofacial surgery.

Genetic requirement for Mycl and efficacy of RNA Pol I inhibition in mouse models of small cell lung cancer.

Small cell lung cancer (SCLC) is a devastating neuroendocrine carcinoma. MYCL (L-Myc) is frequently amplified in human SCLC, but its roles in SCLC progression are poorly understood. We isolated preneoplastic neuroendocrine cells from a mouse model of SCLC and found that ectopic expression of L-Myc, c-Myc, or N-Myc conferred tumor-forming capacity. We focused on L-Myc, which promoted pre-rRNA synthesis and transcriptional programs associated with ribosomal biogenesis. Deletion of Mycl in two genetically engineered models of SCLC resulted in strong suppression of SCLC. The high degree of suppression suggested that L-Myc may constitute a therapeutic target for a broad subset of SCLC. We then used an RNA polymerase I inhibitor to target rRNA synthesis in an autochthonous Rb/p53-deleted mouse SCLC model and found significant tumor inhibition. These data reveal that activation of RNA polymerase I by L-Myc and other MYC family proteins provides an axis of vulnerability for this recalcitrant cancer.

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 .

Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Expression of leptin receptor in renal tubules is sparse but implicated in leptin-dependent kidney gene expression and function.

Leptin regulates energy balance via leptin receptors expressed in central and peripheral tissues, but little is known about leptin-sensitive kidney genes and the role of the tubular leptin receptor (Lepr) in response to a high-fat diet (HFD). Quantitative RT-PCR analysis of Lepr splice variants A, B, and C revealed a ratio of ∼100:10:1 in the mouse kidney cortex and medulla, with medullary levels being ∼10 times higher. Leptin replacement in ob/ob mice for 6 days reduced hyperphagia, hyperglycemia, and albuminuria, associated with normalization of kidney mRNA expression of molecular markers of glycolysis, gluconeogenesis, amino acid synthesis, and megalin. Normalization of leptin for 7 h in ob/ob mice did not normalize hyperglycemia or albuminuria. Tubular knockdown of Lepr [Pax8-Lepr knockout (KO)] and in situ hybridization revealed a minor fraction of Lepr mRNA in tubular cells compared with endothelial cells. Nevertheless, Pax8-Lepr KO mice had lower kidney weight. Moreover, while HFD-induced hyperleptinemia, increases in kidney weight and glomerular filtration rate, and a modest blood pressure lowering effect were similar compared with controls, they showed a blunted rise in albuminuria. Use of Pax8-Lepr KO and leptin replacement in ob/ob mice identified acetoacetyl-CoA synthetase and gremlin 1 as tubular Lepr-sensitive genes that are increased and reduced by leptin, respectively. In conclusion, leptin deficiency may increase albuminuria via systemic metabolic effects that impinge on kidney megalin expression, whereas hyperleptinemia may induce albuminuria by direct tubular Lepr effects. Implications of Lepr variants and the novel tubular Lepr/acetoacetyl-CoA synthetase/gremlin 1 axis remain to be determined.NEW & NOTEWORTHY This study provides new insights into kidney gene expression of leptin receptor splice variants, leptin-sensitive kidney gene expression, and the role of the leptin receptor in renal tubular cells for the response to diet-induced hyperleptinemia and obesity including albuminuria.

Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations.

BACKGROUND: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. METHODS: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy. RESULTS: As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment. CONCLUSIONS: Among patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.).

Impact of Dynamic Tongue Reconstruction on Sequential Changes of Swallowing Function in Patients Undergoing Total or Near-Total Glossectomy.

PURPOSE: This study aimed to compare the effects of motor-innervated free flap on sequential changes of swallowing function in patients undergoing total or near-total glossectomy with laryngeal preservation. MATERIALS AND METHODS: The medical charts of 21 patients who underwent tongue reconstruction after total or near-total glossectomy between April 2015 and December 2020 were retrospectively reviewed. Patients were divided into groups by reconstruction type: conventional, reconstruction using an anterolateral thigh free flap (n = 11), and dynamic, reconstruction using an anterolateral thigh with innervated vastus lateralis flap (n = 10). Demographics, surgical details, and survival outcomes were investigated. A videofluoroscopic penetration-aspiration scale and functional outcome swallowing scale were analyzed according to postoperative time courses, classified as within 6 months, 6 to 12 months, and after 12 months postoperative. A time-to-event analysis was performed for gastrostomy tube status. RESULTS: The dynamic group showed improved swallowing outcomes at 6 to 12 months postoperative (dynamic vs conventional group, penetration-aspiration scale: 3 ± 1.51 vs 6 ± 1.63, P = 0.024; functional outcome swallowing scale: 1.89 ± 1.36 vs 4 ± 1.41, P = 0.009). In the multivariate analysis, the dynamic group showed a decreased probability of decompensated swallowing function at 6 to 12 months postoperative (odds ratio, 0.062; 95% confidence interval, 0.004-1.084; P = 0.057). A time-to-event analysis revealed no significant difference in gastrostomy tube status between the dynamic and the conventional group. CONCLUSIONS: Considering higher mortality in patients subjected to total or near-total glossectomy, dynamic reconstruction with motor-innervated free flap is worth to perform in terms of enhancing the swallowing function within 1-year postoperative period, thereby improving the quality of life.

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.

Dual Application of Patient-Specific Occlusion-Based Positioning Guide and Fibular Cutting Guide for Accurate Reconstruction of Segmental Mandibular Defect.

In this study, the authors introduced a dual application of patient-specific occlusion-based positioning guide and fibular cutting guide to obtain ideal occlusal relationship and mandibular contour in patients undergoing mandibular reconstruction. A retrospective review was performed in 21 patients who underwent mandibular reconstruction with a fibular osteocutaneous free flap. Using computed tomography and intraoral scanning data, fibular cutting guide and occlusion-based positioning guide were simulated in a modeling software and 3-dimensionally printed. Both guides were applied in 9 patients, defined as dual guide group, while the fibular cutting guide was solely used in the remaining patients, defined as single guide group. Functional outcomes including occlusion status, trismus, presence of osseointegrated implant were assessed at 1-year postoperative period. To evaluate the accuracy of the reconstruction, the discrepancy between the planned simulation and actual surgical result was quantified by measuring mandibular deviation angle and volume conformity. Regarding the functional outcomes, all patients in dual guide group showed satisfactory occlusion and intact oral capacity at postoperative 1-year assessment, while 3 patients in single guide group had prolonged malocclusion. The dual guide group showed significantly decreased deviation angle in coronal (right side, 2.93°±1.98° vs. 7.02°±2.81°, P =0.003) and axial plane (right side, 3.20°±2.04° vs. 7.63°±3.40°, P =0.006). The mean volume conformity between the simulation and actual fibular object was significantly higher in the dual guide group (75.27%±6.12% vs. 59.06%±8.57%, P =0.001). In conclusion, the use of occlusion-based positioning guide combined with the fibular cutting guide can enhance the accuracy of mandible reconstruction and functional outcomes.

A Novel Bone Contouring Technique Using Multiple Tangential Shaving for Conservative Management of Craniofacial Fibrous Dysplasia.

This study aimed to propose a novel surgical technique, named multiple tangential shaving of bone contour, for the conservative management of craniofacial fibrous dysplasia. We retrospectively reviewed 17 patients who underwent conservative management of craniofacial fibrous dysplasia using multiple tangential shaving technique between July 2005 and December 2020. Demographics, tumor characteristics, and surgery-related factors were investigated. All patients underwent preoperative (T0) and postoperative computed tomography scans taken at least twice within 1 month for immediate assessment (T1) and at least 12 months postoperatively for long-term assessment (T2). Clinical outcomes, including tumor recurrence, perioperative complications, and physician measure of esthetic outcomes (Whitaker score), were investigated. This technique was applied for contouring of the zygomatic-maxillary and calvarial bone for patients aged between 16 and 60 years (mean age: 26 y). The mean±SD tumor volume reduction was 15.5±8.95 cm 3 , and the postoperative mean±SD tumor growth rate was 5.52±6.26% per year. Satisfactory outcome was obtained in terms of esthetics with a mean±SD Whitaker score of 1.41±0.62. Patients required a mean operation time of 1.67±0.43 hours and a mean number of shaving operations of 1.35±0.61 during the follow-up period. Five of 17 patients required reoperation because of the tumor recurrence (N=4) and to correct new-onset diplopia after surgery (N=1). In conclusion, the multiple tangential shaving technique allows an easy approach for conservative management of craniofacial fibrous dysplasia. An acceptable rate of tumor recurrence and esthetic outcomes can be obtained by selecting the appropriate candidate for a conservative approach.

Extended Superficial Musculoaponeurotic System Face-Lift With Vertical Vector for Asian Patients: A 3-Dimensional Analysis of Facial Contour.

In this study, the authors report the experience of extended superficial musculoaponeurotic system (SMAS) face-lift with the vertical vector in Asian ethnicity and investigate the 3-dimensional change of facial contour. A total of 32 patients with Korean ethnicity underwent extended SMAS face-lift with vertical vector from 2015 to 2018. Patients with aging face were included for the study subjects, whereas those who were diagnosed with any craniofacial deformity were excluded. Using 3-dimensional photogrammetry, surface contour analysis was performed in the cheek region to calculate the mean, maximal, and minimal difference of surface projection and global root mean square error between the preoperative and 1-year postoperative period. The change of horizontal facial widths and jawline angle was evaluated. In contour analysis, the mean difference of surface contour was highest in anterior, followed by lateral cheek and lower face, sequentially. The maximal difference of surface contour was highest in anterior cheek, followed by lateral cheek and lower face, whereas the minimal difference of surface contour was lowest in lower face, followed by anterior cheek and lateral cheek, sequentially. No significant differences in the midfacial and lower facial distances were observed between the preoperative and postoperative periods. There was significant increase of jawline angle, from 20.78 to 23.14 degree of mean value ( P =0.001). In conclusion, the extended SMAS face-lift with vertical vector can be an optimal option for Asian subjects in terms of the midfacial volumetric shift, sharpening of jawline and avoidance of midfacial widening.

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.

Are We Correctly Measuring Mandibular Stability After Surgery-First Approach? A Comparative Study Based on Novel 3-Dimensional Measurements.

Using traditional measures to assess mandibular stability after the surgery-first approach (SFA) may produce inaccurate results because unlike the conventional orthodontic-first approach (OFA), the main dental movements occur after surgery in SFA, which produce unavoidable mandibular movements, especially in cases with postsurgical premature dental contact. As these movements are part of the surgical-orthodontic plan, they should not be considered an actual relapse. In this study, to avoid postsurgical dental movement effects, the authors used the relationship between proximal and distal mandibular segments to evaluate stability after SFA. Four easily located points on computerized tomography/cone-beam computerized tomography reconstructed 3-dimensional images were used to calculate 4 measurements between proximal and distal mandibular segments across the osteotomy line in two matched groups of patients (SFA and OFA) at 3 different time points (before, immediately after, and 1 year after the surgery). A high level of skeletal stability was found in the SFA group, with changes 1 year after surgery not exceeding 0.5 mm. The SFA was as skeletally stable as OFA, and the mandibular counterclockwise rotation after surgery was related to the planned dental movements and not the instability of the surgery itself. To avoid the illusion of this preplanned relapse, stability should be measured as a relation between proximal and distal mandibular segments, across the osteotomy and fixation line, and not as a relation between maxillary and mandibular landmarks or between the mandible and facial planes as classically described.