Correction: Masticatory muscle index for indicating skeletal muscle mass in patients with head and neck cancer.

[This corrects the article DOI: 10.1371/journal.pone.0251455.].

The impact of sarcopenia on overall survival in patients with pan-RAS wild-type colorectal liver metastasis receiving hepatectomy.

Sarcopenia has been associated with conventional chemotherapy-related toxicity, postoperative complications and poor overall survival in patients with genotype-unselected metastatic colorectal cancer (mCRC). This study aimed to evaluate the prognostic implications of sarcopenia and its change after perioperative cetuximab plus doublet chemotherapy and hepatectomy in patients with RAS wild-type colorectal liver metastasis (CRLM). Patients with CRLM from 2007 to 2018 in Chang Gung Research Database were retrospectively analyzed. Baseline characteristics as well as skeletal muscle index (SMI) at baseline and dynamic changes after interventions were collected. A multivariate Cox proportional hazard model was used to evaluate the effect of each parameter on overall survival (OS), and the Kaplan-Meier method was used to establish survival curves. A two-sided p value < 0.05 was considered statistically significance. Of 214 RAS wild-type mCRC patients who received both cetuximab and doublet chemotherapy, 77 who received upfront or subsequent hepatectomy were included in this study. The median follow-up time was 2.3 years. The rate of sarcopenia was higher in the patients who received neoadjuvant cetuximab-containing regimens than in those who received upfront hepatectomy (95% versus 63%, p = 0.001). Increased SMI after perioperative systemic therapy remained independently associated with better OS in multivariate analysis [hazard ratio (HR) = 0.27/10% increase, p = 0.013). The patients with sarcopenia had a trend of worse OS than those without sarcopenia (median OS: 4.5 versus 3.6 years, log-rank p = 0.282). Improvement in sarcopenia ([SMI after intervention - initial SMI]/initial SMI × 100%) is an important prognostic factor for OS. Future research is warranted to investigate direct interventions for sarcopenia and the impact on OS.

Targeting the EGFR-ERK axis using the compatible solute ectoine to stabilize CFTR mutant F508del.

Mutations in the CFTR gene lead to cystic fibrosis, a genetic disease associated with chronic infection and inflammation and ultimately respiratory failure. The most common CF-causing mutation is F508del and CFTR modulators (correctors and potentiators) are being developed to rescue its trafficking and activity defects. However, there are currently no modulators that stabilize the rescued membrane F508del-CFTR which is endocytosed and quickly degraded resulting in a shorter half-life than wild-type (WT). We previously reported that the extracellular signal-regulated kinase (ERK) MAPK pathway is involved in CFTR degradation upon cigarette smoke exposure. Interestingly, we found that ERK phosphorylation was increased in CF human bronchial epithelial (HBE) cells (CF-HBE41o- and primary CF-HBE) compared to non-CF controls, and this was likely due to signaling by the epidermal growth factor receptor (EGFR). EGFR can be activated by several ligands, and we provide evidence that amphiregulin (AREG) is important for activating this signaling axis in CF. The natural osmolyte ectoine stabilizes membrane macromolecules. We show that ectoine decreases ERK phosphorylation, increases the half-life of rescued CFTR, and increases CFTR-mediated chloride transport in combination with the CFTR corrector VX-661. Additionally, ectoine reduces production of AREG and interleukin-8 by CF primary bronchial epithelial cells. In conclusion, EGFR-ERK signaling negatively regulates CFTR and is hyperactive in CF, and targeting this axis with ectoine may prove beneficial for CF patients.

Prognostic Role of High-Sensitivity Modified Glasgow Prognostic Score for Patients With Operated Oral Cavity Cancer: A Retrospective Study.

AIM: We probed the prognostic value of the preoperative high-sensitivity modified Glasgow prognostic score (HS-mGPS), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) for patients with oral cavity squamous cell carcinoma (OSCC) to identify patients with the highest risk of having poor survival outcomes. MATERIALS AND METHODS: We executed a retrospective assessment of the records of 303 patients with OSCC who had been subjected to curative surgery between January 2008 and December 2017. The HS-mGPS was categorized using C-reactive protein and albumin thresholds of 3 mg/L and 35 g/L, respectively. Moreover, receiver operating characteristic curve analyses were executed to find out the optimal PLR and NLR cutoffs. We plotted survival curves and compared them through the use of the Kaplan-Meier method and log-rank test, respectively. Through a Cox proportional hazard model, we identified prognostic variables. We also plotted a nomogram comprising the HS-mGPS and clinicopathological factors and assessed its performance with the concordance index. RESULTS: The PLR and NLR cutoffs were 119.34 and 4.51, respectively. We noted an HS-mGPS of 1-2 to be associated with a shorter median overall survival (OS) and disease-fee survival (DFS) compared with an HS-mGPS of 0. Multivariate analysis revealed that an HS-mGPS of 1-2 and an NLR of ≥4.51 were independent risk factors related to poor OS and DFS. The HS-mGPS appeared to have better prognostic effect than did the PLR and NLR, and the combination of the HS-mGPS and NLR appeared to exhibit optimal discriminative ability for OS prognostication. The nomogram based on the HS-mGPS and NLR yielded accurate OS prediction (concordance index = 0.803). CONCLUSION: Our findings suggest that preoperative HS-mGPS is a promising prognostic biomarker of OSCC, and the nomogram comprising the HS-mGPS and NLR provided accurate individualized OSCC survival predictions.

Changes in cardiovascular mortality in Chile during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 pandemic has impacted regular cardiovascular healthcare access and delivery. Service utilisation has declined, and excess cardiovascular mortality has been reported in several countries. We aim to estimate excess cardiovascular deaths in Chile during 2020. METHODS: We collected mortality data from the Chilean Department of Statistics and Health Information and refined them using the maps of Global Burden of Disease Studies in 2017 and 2010. We conducted a time series analysis using quasi-Poisson distribution to predict cardiovascular mortality in 2020 and compared it with observed numbers and calculated attributable fractions (AFs) with 95% uncertainty intervals, as a whole and by sex, age group and type of cardiovascular disease. RESULTS: During 2015-2020, 173 283 cardiovascular deaths were recorded, with 28 141 deaths in 2020. The observation in 2020 was lower than our projection in the overall data (-4.0% (-5.0% to -2.8%)) and in male (-11.7% (-13% to -10.3%)). However, positive AFs were noted among female (5.0% (3.2% to 6.8%)), people in age group 80-89 years (11.0% (8.6% to 13.5%)) and people who died from hypertensive heart diseases (18.9% (14.7% to 23.5%)). CONCLUSIONS: Less overall cardiovascular deaths were observed in 2020 compared with our projection, possibly associated with competing risks from COVID-19 infection in men. Nonetheless, excess cardiovascular deaths were observed among women, people in the age group 80-89 years and people who died from hypertensive heart diseases suggesting possible negative cardiovascular impacts brought by the pandemic on these vulnerable groups.

Preoperative prognostic nutritional index predicts prognosis of patients with oral cavity cancer.

OBJECTIVE: To investigate whether prognostic nutritional index (PNI) predicts patient survival outcomes in oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The data of a total of 360 patients subjected to primary surgery for OSCC were retrospectively analysed. Patients were categorised into high-PNI (≥51.75) and low-PNI (<51.75) groups based on the PNI cut-off value attained from receiver operating characteristic analyses (p < .001), and the intergroup differences in clinicopathological features were determined. The Kaplan-Meier method and Cox proportional hazard model were employed to determine the survival prediction ability of the PNI, and a nomogram based on the PNI was established for individualised survival prediction. RESULTS: A low PNI was noted to exhibit a significant association with shorter overall survival (OS) and disease-free survival (DFS) (both p < .001). Multivariate Cox analyses showed that a lower PNI independently indicated shorter OS and DFS (hazard ratio [HR] = 2.187; p = .001 and HR = 1.459; p = .023, respectively). The concordance index and calibration plots of the PNI-based nomogram revealed the high discriminative ability for OS. CONCLUSIONS: Preoperative PNI is a valuable biomarker for predicting OSCC prognosis, and the proposed PNI-based nomogram can provide individualised prognostic prediction.

Masticatory muscle index for indicating skeletal muscle mass in patients with head and neck cancer.

BACKGROUND: A typical assessment for sarcopenia involves the use of abdominal computed tomography (CT) for calculating the skeletal muscle index (SMI) at the level of the third lumbar vertebra (L3). However, abdominal CT is not regularly performed on patients with head and neck cancer (HNC). We investigated whether masticatory SMI (M-SMI) measurements based on head and neck CT scans can be used to conduct sarcopenia assessments by evaluating whether M-SMI is correlated with L3-SMI. METHODS: Abdominal and head and neck CT images of patients with trauma (n = 50) and HNC (n = 52) were analyzed retrospectively. Both manual delineation and threshold selection methods were used to measure cross-sectional areas of masticatory muscles and those of muscles at the L3 level on CT images. Muscle cross-sectional areas were normalized to height squared to calculate SMI, and a multivariate linear regression model was established to evaluate the correlation between the M-SMI and L3-SMI. Receiver operating characteristic curve analysis was used to assess the ability of the M-SMI to identify sarcopenia, and Cox logistic regression was used to identify predictors of sarcopenia. RESULTS: Patients with HNC had significantly lower M-SMI and L3-SMI than did patients with trauma (p = 0.011 and 0.03, respectively). M-SMI and L3-SMI were strongly correlated (r = 0.901, p < 0.001); in the multivariate model that included sex, the correlation was stronger (r = 0.913, p < 0.001). The associations of sarcopenia with a lower M-SMI (p < 0.001), male sex (p = 0.028), and advanced age (p = 0.011) were significant, and multivariate logistic analysis demonstrated that an M-SMI of <5.5 was an independent predictor of sarcopenia (hazard ratio = 5.37, p < 0.001). CONCLUSIONS: M-SMI assessment in routine head and neck CT scans is feasible and can be an alternative for detecting sarcopenia in patients with HNC.

Prognostic Value of Third Cervical Vertebra Skeletal Muscle Index in Oral Cavity Cancer: A Retrospective Study.

OBJECTIVES/HYPOTHESIS: To assess the prognostic utility of third cervical vertebra skeletal muscle index (C3 SMI) measured from preoperative head and neck computed tomography (CT) in patients with oral cavity squamous cell carcinoma (OSCC). STUDY DESIGN: Retrospective study. METHODS: We retrospectively reviewed the medical records of 125 patients who underwent primary curative surgery for OSCC between 2009 and 2017. Their preoperative C3 SMI was calculated by adjusting the C3 cross-sectional area delineated on head and neck CT by body height squared. A Cox proportional hazard model was employed to identify prognostic factors, and a novel nomogram based on C3 SMI was built for individualized survival prediction. RESULTS: In Kaplan-Meier analysis, high C3 SMI was significantly associated with higher 5-year disease-free survival (DFS) and overall survival (OS) than low C3 SMI. In multivariate analysis, low C3 SMI was an independent risk factor for poor DFS and OS (hazard ratio [HR]: 2.197; 95% confidence interval [CI], 1.170-4.512, P = .032 and HR: 2.143; 95% CI, 1.232-3.728, P = .007, respectively). The concordance-index (C-index) of the nomogram based on C3 SMI was 0.814 for OS, higher than that of the nomogram based on tumor-node-metastasis staging alone (C-index = 0.731). CONCLUSIONS: C3 SMI might serve as a novel prognosticator in OSCC patients undergoing curative surgery, and the nomogram based on C3 SMI might provide good prognostic discrimination ability for individualized survival prediction. LEVEL OF EVIDENCE: IV Laryngoscope, 131:E2257-E2265, 2021.

Robotic Transanal Minimally Invasive Surgery for Rectal Lesions.

Background. Transanal minimally invasive surgery (TAMIS) was developed as a less aggressive alternative treatment for rectal lesions. The purpose of this study was to report the results of robotic TAMIS for such patients. Methods. Patients eligible for TAMIS were operated on using the da Vinci robotic surgical system and GelPOINT Path Transanal Access Platform. Patient demographics, lesion characteristics, perioperative data, complications, and follow-up of all patients were recorded retrospectively. Results. Between March 2015 and August 2018, 24 patients underwent robotic TAMIS by using the da Vinci Si or Xi. The median operative time was 129.6 minutes, and the estimated blood loss was minimal. The mean length of hospital stay was 4.6 days, with no operative complications and no 30-day mortality. There were no statistically significant differences in clinical results and pathological outcomes between the 2 generations of da Vinci systems. Conclusions. With the use of robotic technology, transanal local excision for rectal lesions can be performed with relative ease and safety and can be potentially decreasing the morbidity associated with more aggressive surgical techniques.

Gender differences in the acquisition of suturing skills with the da Vinci surgical system.

BACKGROUND: The percentage of female medical students has been significant elevating worldwide. The demographic shift is expected to influence the proportion of male versus female surgeons soon. The objective of this study was to evaluate the gender differences in the acquisition of robotic suturing skills. METHODS: We compared the robotic suturing performance between 39 male and 19 female medical students. We separated the training into two parts: phase I, involving virtual reality (VR) robotic simulation, and phase II, involving robotic dry-laboratory simulation training. Participants first conducted step-by-step exercises on the VR robotic simulator and then the robotic skin-suturing pad using the da Vinci robot. RESULTS: The metric analysis of the VR task "suture sponge" showed that female students required less time (difference: -170.7 seconds, 95% CI: -247.4 to -94.0) and had fewer errors (error difference: -50, 95% CI: -74.2 to -25.8) to complete the suture sponge exercise compared to male students. Moreover, female students completed more stitches than male students (differences in mean stitch achieved: .35; 95% CI: .06 to .65). However, there was no difference in the quality scores of stitches by gender (p = 0.85). CONCLUSION: Female medical students performed better in the VR task of suture spongy and achieved more stitches than male students with the da Vinci system despite no difference in robotic suture quality by gender. Because this is the first study comparing gender performance on a robotic platform, further studies are required to investigate if different training approaches will affect the performance by gender.

Automatic Machine-Learning-Based Outcome Prediction in Patients With Primary Intracerebral Hemorrhage.

Background: A predictive model can provide physicians, relatives, and patients the accurate information regarding the severity of disease and its predicted outcome. In this study, we used an automated machine-learning-based approach to construct a prognostic model to predict the functional outcome in patients with primary intracerebral hemorrhage (ICH). Methods: We retrospectively collected data on demographic characteristics, laboratory studies and imaging findings of 333 patients with primary ICH. The functional outcomes at the 1st and 6th months after ICH were defined by the modified Rankin scale. All of the attributes were used for preprocessing and for automatic model selection with Automatic Waikato Environment for Knowledge Analysis. Confusion matrix and areas under the receiver operating characteristic curves (AUC) were used to test the predictive performance. Results: Among the models tested, the random forest provided the best predictive performance for functional outcome. The overall accuracy for predicting the 1st month outcome was 83.1%, with 77.4% sensitivity and 86.9% specificity, and the AUC was 0.899. The overall accuracy for predicting the 6th month outcome was 83.9%, with 72.5% sensitivity and 90.6% specificity, and the AUC was 0.917. Conclusions: Using an automatic machine learning technique to predict functional outcome after ICH is feasible, and the random forest model provides the best predictive performance across all tested models. This prediction model may provide information regarding functional outcome for clinicians that will help provide appropriate medical care for patients and information for their caregivers.

Reduced expression of the Ion channel CFTR contributes to airspace enlargement as a consequence of aging and in response to cigarette smoke in mice.

Chronic Obstructive Pulmonary Disease (COPD) is a complex disease resulting in respiratory failure and represents the third leading cause of global death. The two classical phenotypes of COPD are chronic bronchitis and emphysema. Owing to similarities between chronic bronchitis and the autosomal-recessive disease Cystic Fibrosis (CF), a significant body of research addresses the hypothesis that dysfunctional CF Transmembrane Conductance Regulator (CFTR) is implicated in the pathogenesis of COPD. Much less attention has been given to emphysema in this context, despite similarities between the two diseases. These include early-onset cellular senescence, similar comorbidities, and the finding that CF patients develop emphysema as they age. To determine a potential role for CFTR dysfunction in the development of emphysema, Cftr+/+ (Wild-type; WT), Cftr+/- (heterozygous), and Cftr-/- (knock-out; KO) mice were aged or exposed to cigarette smoke and analyzed for airspace enlargement. Aged knockout mice demonstrated increased alveolar size compared to age-matched wild-type and heterozygous mice. Furthermore, both heterozygous and knockout mice developed enlarged alveoli compared to their wild-type counterparts following chronic smoke exposure. Taken into consideration with previous findings that cigarette smoke leads to reduced CFTR function, our findings suggest that decreased CFTR expression sensitizes the lung to the effects of cigarette smoke. These findings may caution normally asymptomatic CF carriers against exposure to cigarette smoke; as well as highlight emphysema as a future challenge for CF patients as they continue to live longer. More broadly, our data, along with clinical findings, may implicate CFTR dysfunction in a pathology resembling accelerated aging.

Robotic transanal minimally invasive surgery for rectal cancer after clinical complete response to neoadjuvant chemoradiation.

BACKGROUND: Full-thickness local excision (FTLE) for rectal cancer showing clinical complete remission (cCR) after neoadjuvant chemoradiation therapy (NCRT) is associated with good oncological results. The purpose of this study was to report the results of robotic transanal minimally invasive surgery for such patients. METHODS: Patients were treated with a 5-fluorouracil-based NCRT regimen. The determination of cCR was based on digital rectal examination, colonoscopy, and magnetic resonance imaging. RESULTS: Six patients underwent transanal FTLE using the da Vinci Xi surgical system. The median operative time was 106.5 minutes, and the estimated blood loss was minimal. The mean length of hospital stay was 4.2 days. After 18.2 months of follow-up, none of the patients developed local recurrences or distant disease. CONCLUSIONS: With the use of robotic technology, FTLE can be performed with relative ease and can be considered as a viable alternative to radical resection or a "Watch and Wait" strategy.

The psychoactive substance of cannabis Δ9-tetrahydrocannabinol (THC) negatively regulates CFTR in airway cells.

BACKGROUND: Marijuana consumption is on the rise in the US but the health benefits of cannabis smoking are controversial and the impact of cannabis components on lung homeostasis is not well-understood. Lung function requires a fine regulation of the ion channel CFTR, which is responsible for fluid homeostasis and mucocilliary clearance. The goal of this study was to assess the effect that exposure to Δ9-tetrahydrocannabinol (THC), the psychoactive substance present in marijuana, has on CFTR expression and function. METHODS: Cultures of human bronchial epithelial cell line 16HBE14o- and primary human airway epithelial cells were exposed to THC. The expression of CFTR protein was determined by immunoblotting and CFTR function was measured using Ussing chambers. We also used specific pharmacological inhibitors of EGFR and ERK to determine the role of this pathway in THC-induced regulation of CFTR. RESULTS: THC decreased CFTR protein expression in primary human bronchial epithelial cells. This decrease was associated with reduced CFTR-mediated short-circuit currents. THC also induced activation of the ERK MAPK pathway via activation of EGFR. Inhibition of EGFR or MEK/ERK prevented THC-induced down regulation of CFTR protein expression. CONCLUSIONS AND GENERAL SIGNIFICANCE: THC negatively regulates CFTR and this is mediated through the EGFR/ERK axis. This study provides the first evidence that THC present in marijuana reduces the expression and function of CFTR in airway epithelial cells.

Association of Chronic Kidney Disease With Small Vessel Disease in Patients With Hypertensive Intracerebral Hemorrhage.

BACKGROUND: Chronic kidney disease (CKD) has been closely associated with hypertension and stroke. Although studies have reported the relationship between CKD and cerebral small vessel disease (SVD), the link between CKD, hypertension, and SVD is uncertain. The aim of this study was to investigate the association between CKD and SVD in patients with strictly hypertensive intracerebral hemorrhage (ICH). METHODS: 142 patients with acute hypertensive ICH were enrolled in this study. Magnetic resonance imaging was performed to assess imaging markers for SVD. Patients were categorized into three CKD groups based on the degree of kidney dysfunction [glomerular filtration rate (GFR) in milliliters per minute per 1.73 m2]: normal kidney function (GFR ≥ 90), mild kidney disease (60 ≤ GFR < 90), and moderate to severe kidney disease (GFR < 60). RESULTS: The prevalence rate of mild and moderate to severe CKD was 50 and 14.8%, respectively. The stage of CKD was associated with history of chronic hypertension (p = 0.046) as well as the prevalence rate of overall and deep cerebral microbleed (CMB) (p = 0.001 and p = 0.002, respectively). The stage of CKD was a significant risk factor for deep white matter hyperintensity (WMH) (OR 1.848; 95% CI 1.022-3.343, p = 0.042), overall CMB (OR 2.628; 95% CI 1.462-4.724, p = 0.001), lobar CMB (OR 2.106; 95% CI 1.119-3.963, p = 0.021), and deep CMB (OR 2.237; 95% CI 1.263-3.960, p = 0.006), even after adjustment for confounders. CONCLUSION: In patients with hypertensive ICH, the prevalence of CKD is high even at the early stage of renal function impairment and is associated with the prevalence of CMB and deep WMH. These results reinforce the notion of a link between hypertensive vasculopathy, renal function impairment, and cerebral SVD.

Accuracy of Presurgical Functional MR Imaging for Language Mapping of Brain Tumors: A Systematic Review and Meta-Analysis.

Purpose To compare functional magnetic resonance (MR) imaging for language mapping (hereafter, language functional MR imaging) with direct cortical stimulation (DCS) in patients with brain tumors and to assess factors associated with its accuracy. Materials and Methods PubMed/MEDLINE and related databases were searched for research articles published between January 2000 and September 2016. Findings were pooled by using bivariate random-effects and hierarchic summary receiver operating characteristic curve models. Meta-regression and subgroup analyses were performed to evaluate whether publication year, functional MR imaging paradigm, magnetic field strength, statistical threshold, and analysis software affected classification accuracy. Results Ten articles with a total of 214 patients were included in the analysis. On a per-patient basis, the pooled sensitivity and specificity of functional MR imaging was 44% (95% confidence interval [CI]: 14%, 78%) and 80% (95% CI: 54%, 93%), respectively. On a per-tag basis (ie, each DCS stimulation site or "tag" was considered a separate data point across all patients), the pooled sensitivity and specificity were 67% (95% CI: 51%, 80%) and 55% (95% CI: 25%, 82%), respectively. The per-tag analysis showed significantly higher sensitivity for studies with shorter functional MR imaging session times (P = .03) and relaxed statistical threshold (P = .05). Significantly higher specificity was found when expressive language task (P = .02), longer functional MR imaging session times (P < .01), visual presentation of stimuli (P = .04), and stringent statistical threshold (P = .01) were used. Conclusion Results of this study showed moderate accuracy of language functional MR imaging when compared with intraoperative DCS, and the included studies displayed significant methodologic heterogeneity. © RSNA, 2017 Online supplemental material is available for this article.

Correction: The learning curve of endoscopic total mastectomy in Taiwan: A multi-center study.

[This corrects the article DOI: 10.1371/journal.pone.0178251.].

The learning curve of endoscopic total mastectomy in Taiwan: A multi-center study.

INTRODUCTION: Laparoscopic techniques are commonly used in abdominal and gynecologic surgery, while breast cancer surgery has remained largely unchanged. In Asia, especially in Japan, many surgeons have started to use endoscopic surgery for breast cancer. In Taiwan, endoscopy-assisted breast surgery started in 2010. The benefits of this surgical method include smaller incisions, an axillary anatomic approach, clear vision, no oncologic compromise, and good cosmetic outcomes. This is the first report to discuss the learning curve of endoscopy-assisted breast surgery, including the difficulties experienced. MATERIALS AND METHODS: From June 2011 to December 2013, data were collected from 134 patients who received an endoscopic total mastectomy at the Taipei Medical University Hospital (TMUH) or Changhua Christian Hospital (CCH). We divided these patients into a learning group (TMUH, n = 15; CCH, n = 15) and a mature group (TMUH, n = 50; CCH, n = 54). Patient data and perioperative variables were recorded by retrospective chart review. Variables were compared using the χ2 test and Student's t-test. RESULTS: There was a significant difference in operation time (275.3 vs. 228.9 minutes, p < 0.01) between the learning and mature groups. Perioperative variables (lymph node dissection method, nipple preservation, and reconstruction method) were also analyzed, but there were no demographic differences between the groups. The complication rate was higher in the learning group, although this difference was also not statistically significant. CONCLUSION: Our study is the first to discuss the learning curve of endoscopic total mastectomy. The operation time decreased significantly after 15 cases at each hospital. Although the operation is still more time-consuming than traditional methods, it has the benefit of smaller wounds and improved cosmetic outcomes if combined with immediate reconstruction.

Fully Automatic System for Accurate Localisation and Analysis of Cephalometric Landmarks in Lateral Cephalograms.

Cephalometric tracing is a standard analysis tool for orthodontic diagnosis and treatment planning. The aim of this study was to develop and validate a fully automatic landmark annotation (FALA) system for finding cephalometric landmarks in lateral cephalograms and its application to the classification of skeletal malformations. Digital cephalograms of 400 subjects (age range: 7-76 years) were available. All cephalograms had been manually traced by two experienced orthodontists with 19 cephalometric landmarks, and eight clinical parameters had been calculated for each subject. A FALA system to locate the 19 landmarks in lateral cephalograms was developed. The system was evaluated via comparison to the manual tracings, and the automatically located landmarks were used for classification of the clinical parameters. The system achieved an average point-to-point error of 1.2 mm, and 84.7% of landmarks were located within the clinically accepted precision range of 2.0 mm. The automatic landmark localisation performance was within the inter-observer variability between two clinical experts. The automatic classification achieved an average classification accuracy of 83.4% which was comparable to an experienced orthodontist. The FALA system rapidly and accurately locates and analyses cephalometric landmarks in lateral cephalograms, and has the potential to significantly improve the clinical work flow in orthodontic treatment.