Beneficial Effects of Concomitant Long-Acting Injectable Antipsychotics on Time to Rehospitalization in Patients With Treatment-Resistant Schizophrenia Receiving Clozapine: A Retrospective Cohort Study.

Introduction: This study aimed to assess the association between long-acting injectable (LAI) antipsychotic prescription and the risk of psychiatric hospitalization in patients with treatment-resistant schizophrenia (TRS) receiving clozapine.Methods: In this retrospective cohort study at a single tertiary psychiatric center, we analyzed rehospitalization hazard ratios (HRs) in refractory schizophrenia patients, classified by DSM-IV-TR and DSM-5 criteria. We examined various psychotropic regimens-clozapine with or without other oral antipsychotics (OAPs) or LAI antipsychotics. Subgroups were stratified by daily clozapine dosage and previous admissions.Results: A total of 719 patients were included in the study. Analyses were conducted on all the patients over 3- month, 6-month, and 1-year periods. Patients treated with a combination of clozapine and LAI antipsychotics (CLO + LAI) had a significantly higher number of previous hospitalizations (P = .003), and a higher daily dose of clozapine (P < .001) was found in the CLO + OAP group than in the CLO (monotherapy) group and the CLO + LAI group. Patients treated with LAI antipsychotic comedication had significantly lower HRs for rehospitalization in 1 year among 3 studied groups. Moreover, the protective effects of LAI antipsychotics were observed in all the subgroups stratified by daily clozapine dosage and number of previous admissions to represent disease severity.Conclusion: The combination of clozapine and LAI antipsychotics was associated with a significantly lower risk of rehospitalization compared to both the combination of clozapine and OAPs and clozapine monotherapy. The use of LAI antipsychotics should be considered to prevent rehospitalization in patients with TRS who are already being treated with clozapine.

Factors Influencing Health Promotion Lifestyle in Female Breast Cancer Survivors: The Role of Health Behavior Self-Efficacy and Associated Factors.

OBJECTIVES: To examine the factors influencing health-promoting lifestyles and the changes in health behavior self-efficacy and health-promoting lifestyles among female breast cancer survivors over a 6-month period. METHODS: A longitudinal design with purposive sampling was deployed. Data collection occurred at the baseline (T1), 3 months (T2), and 6 months (T3). In total, 53 breast cancer survivors agreed to participate. All participants completed the first two rounds of data collection, 49 participants completed data collection at the 6-month mark (T3). The Chinese versions of the Self-Rated Abilities for Health Practices Scale (SRAHP) and the Health-Promoting Lifestyle Profile (HPLP) were used. RESULTS: Health behavior self-efficacy and health-promoting lifestyle scores increased over time. Age, impaired cardiac function, those taking a career break, psychological well-being, and responsible health practice in self-efficacy for health behaviors were significant predictors of health-promoting lifestyle. CONCLUSIONS: Younger breast cancer survivors, those taking a career break, and those with poor health behavior self-efficacy were less likely to engage in a health-promoting lifestyle and may require guidance in improving overall health behaviors. IMPLICATIONS FOR NURSING PRACTICE: Healthcare providers should not only be aware of the suboptimal health promotion lifestyle in breast cancer survivors but also focus on enhancing health behavior self-efficacy. This is particularly crucial for younger breast cancer survivors or those currently unemployed.

Evaluation of healthcare-related factors influencing mental health of Taiwanese citizens among different age groups.

The issue of mental health has gained heightened recognition as a significant public health concern due to its potential to significantly impact various aspects of individuals' lives. Numerous factors may influence mental health, and this study seeks to investigate and compare potential healthcare-related factors that affect the mental health of Taiwanese individuals across different age groups. Data for this study were taken from the Taiwan Social Change Survey (TSCS), conducted in 2021. Descriptive statistics were calculated to compare the three age groups. Then, multiple regression models were constructed with mental health conditions as the dependent variable and demographics and other key healthcare-related components as independent variables, respectively. Results showed that, among the three age groups, the middle-aged adults had the highest BMI, and the older adults had significantly better mental health. As compared with the other age groups, the older adults had significantly better perceptions of fair distribution of healthcare resources, and their trust in the healthcare system was the highest. With regard to searching for online healthcare information, the frequency reported by the older adults was the lowest. The regression model showed that, religious belief, trust in the healthcare system and searching for online healthcare information were significantly associated with mental health of middle-aged adults. In the younger group, searching for online healthcare information was significantly negatively associated with mental health. The study's findings provide insight into how to provide Taiwanese citizens of different age groups with proper and targeted mental health promotion activities.

Effects of aromatherapy on agitation in patients with dementia in the community: A quasi-experimental study.

The behavioral and psychological symptoms of dementia (BPSD) are experienced by up to 90% of patients with dementia throughout dementia. This study aims to investigate the effect of aromatherapy on agitation in patients with dementia in the community. This prospective cohort study was conducted at a single day-care center for patients with dementia located in northern Taiwan with 2-week and 4-week follow-ups, comparing the severity of agitation between 3 measure points as the primary outcome. The aromatherapy was performed over 5 consecutive days for 4 weeks. Throughout the four-week observation were analyzed by GEE. Significant differences were found in the Chinese version of Cohen-Mansfield Agitation Inventory (CCMAI) total agitation score (ß=-3.622, p=0.037) and physically non-aggressive behavior subscale (ß=-4.005, p=0.004) between aromatherapy group and control group. The severity of dementia-related agitation, especially the severity of physically non-aggressive behavior in demented patients, could be significantly reduced by a four-week intervention of aromatherapy.

Diverse genetic spectrum among patients who met the criteria of hereditary breast, ovarian and pancreatic cancer syndrome.

OBJECTIVE: Genetic high-risk assessment combines hereditary breast, ovarian and pancreatic cancer into one syndrome. However, there is a lack of data for comparing the germline mutational spectrum of the cancer predisposing genes between these three cancers. METHODS: Patients who met the criteria of the hereditary breast, ovarian and pancreatic cancer were enrolled and received multi-gene sequencing. RESULTS: We enrolled 730 probands: 418 developed breast cancer, 185 had ovarian cancer, and 145 had pancreatic cancer. Out of the 18 patients who had two types of cancer, 16 had breast and ovarian cancer and 2 had breast and pancreatic cancer. A total of 167 (22.9%) patients had 170 mutations. Mutation frequency in breast, ovarian and pancreatic cancer was 22.3%, 33.5% and 17.2%, respectively. The mutation rate was significantly higher in patients with double cancers than those with a single cancer (p<0.001). BRCA1 and BRCA2 were the most dominant genes associated with hereditary breast and ovarian cancer, whereas ATM was the most prevalent gene related to hereditary pancreatic cancer. Genes of hereditary colon cancer such as lynch syndrome were presented in a part of patients with pancreatic or ovarian cancer but seldom in those with breast cancer. Families with a history of both ovarian and breast cancer were associated with a higher mutation rate than those with other histories. CONCLUSION: The mutation spectrum varies across the three cancer types and family histories. Our analysis provides guidance for physicians, counsellors, and counselees on the offer and uptake of genetic counseling.

Development and validation of the Visual Function Battery for Children with Special Needs.

AIM: To develop and validate the Visual Function Battery for Children with Special Needs (VFB-CSN). METHOD: This was a scale development and validation study with (1) construct and item generation and (2) evaluations of interrater reliability, acceptability, and content, ecological, and convergent validities. RESULTS: Children with special needs were recruited for the reliability (n = 32) and validity (n = 95) investigations. The construct and items were generated based on literature review and an expert panel. We constructed eight categories, namely visual reflex, ocular muscle balance, visual acuity, oculomotor, visual field, contrast sensitivity, colour/form vision, and visual attention. Both functional assessment and standardized tests were adopted. The reliabilities were high for the whole VFB-CSN (intraclass correlation coefficient [ICC] = 0.90, 95% confidence interval [CI] = 0.80-0.90) and good for the oculomotor, contrast sensitivity, and colour/form vision (ICC = 0.80-0.86, 95% CI = 0.50-0.93). Correlations between the VFB-CSN and the Functional Vision Questionnaire were strong and acceptable for the contrast sensitivity, acuity, and colour/form vision (r = 0.79, r = 0.69, r = 0.69, r = 0.70 respectively). The correlation between the VFB-CSN and standardized visual acuity test was acceptable (r = -0.72). INTERPRETATION: The VFB-CSN is a reliable and valid multifaceted battery for children with special needs. Acceptable psychometric properties were also found for the acuity and contrast sensitivity. WHAT THIS PAPER ADDS: The Visual Function Battery for Children with Special Needs (VFB-CSN) can measure several types of visual function. The VFB-CSN also measures varying degrees of visual impairment in children with special needs. The VFB-CSN provides functional assessment and quantitative measurement for children with disability and difficulty in cooperating on standardized tests.

Superior gait performance and balance ability in Latin dancers.

Background: Latin dance consists of various fast and stability-challenging movements that require constant body adjustments to maintain proper posture and balance. Although human gaits are assumed to be symmetrical, several factors can contribute to asymmetrical behavior of the lower extremities in healthy adults. These include lower limb dominance, ground reaction forces, lower limb muscle power, foot placement angle, and range of joint motion. Gait impairment can lead to a high risk of falling, diminished mobility, and even cognition impairment. We hypothesized that Latin dancers might have a more symmetric gait pattern and better balance ability than healthy non-dancer controls. Methods: We investigated the impact of Latin dance training on gait behaviors and body balance. We recruited twenty Latin dancers and 22 normal healthy subjects to conduct walking experiments and one-leg stance tests, and we measured their kinematic data by inertial measurement units. We then defined four performance indexes to assess gait performance and body stability to quantify the potential advantages of dance training. Results: We found that the two gait asymmetric indexes during the walking test and the two performance indexes during the one-leg stance tests were better in Latin dancers compared with the healthy control group. The results confirmed the superiority of Latin dancers over the healthy control group in gait symmetry and balance stability. Our results suggest that Latin dancing training could effectively strengthen lower limb muscles and core muscle groups, thereby improving coordination and enhancing gait performance and balance. Conclusion: Latin dance training can benefit gait performance and body balance. Further studies are needed to investigate the effect of Latin dance training on gait and balance outcomes in healthy subjects and patients with gait disorders.

Dose-response analysis of aripiprazole in patients with schizophrenia in Taiwan.

Background: Aripiprazole is a third-generation antipsychotic agent with acceptable efficacy and a good safety profile. Previous studies have indicated the therapeutic serum concentration of aripiprazole to be 100 to 350 ng/ml; however, most of these studies examined a Western population. Patients with schizophrenia from Tungs' Taichung MetroHarbor Hospital in central Taiwan were recruited to analyze the dose-response relationship of aripiprazole in the Chinese population. Objective: We aimed to investigate whether a serum concentration of aripiprazole higher than the current suggested range leads to higher response rates. Design: A prospective cohort study was designed to investigate the response rates in different studied cohorts grouped by serum concentration of aripiprazole. Data Sources and Methods: Data of 64 patients who presented to a single medical center in central Taiwan and who received therapeutic drug monitoring (TDM) were obtained. Serum concentrations of aripiprazole were correlated with the clinical response of patients by using the Clinical Global Impressions (CGI) scores. Results: The mean concentration of aripiprazole was 432.1 ± 275.1 ng/ml in the study cohort. Among the much-improved patients, the mean serum concentration of aripiprazole was 494 ± 273 ng/ml (25th-75th percentiles 264-666 ng/ml), which was higher than the current recommended therapeutic target of 100-350 ng/ml for aripiprazole. The response rate in the severe group (baseline CGI score of 6 or 7) was significantly higher than in the moderate group (baseline CGI score of 4 or 5; 86.7% versus 55.9%, p = 0.007). Conclusion: A significantly higher response rate was observed in the study cohort with serum aripiprazole concentrations over 300 ng/ml. Therefore, dosing higher than the current recommended range may potentially improve the treatment efficacy in the Chinese population. Because the serum concentration varies among patients due to multiple intrinsic and extrinsic factors, TDM, especially in outpatients, is recommended if the clinical response is limited.

Association of Postpartum Depression with Maternal Suicide: A Nationwide Population-Based Study.

BACKGROUND: To examine the association of postpartum depression (PPD) with maternal suicide in the Taiwanese population. METHODS: We examined the medical records of women aged 18-50 years who experienced childbirth and had PPD (the study cohort, n = 2882), who experienced childbirth but did not have PPD (comparison cohort 1, n = 5764), and who neither experienced childbirth nor had PPD (comparison cohort 2, n = 5764) between 2000 and 2015. The patients were followed up until suicide, withdrawal from the National Health Insurance program, or 31 December 2015. RESULTS: The rates of anxiety and depression symptoms, as well as the cumulative risk of suicide, were significantly higher in the study cohort. PPD was significantly correlated with an increased risk of maternal suicide and was associated with a greater risk of developing comorbidities such as hypertension, diabetes mellitus, hyperlipidemia, and stroke. The comparison cohorts did not differ significantly in terms of suicide risk. CONCLUSION: PPD was associated with a significantly higher rate of suicide and a shorter time to suicide after childbirth. Younger age, winter, and subclinical depression and anxiety positively predicted suicide in the study cohort. To prevent maternal suicide, clinicians should be observant of subclinical depression and anxiety symptoms among patients.

Deep-Learning Approach to Predict Survival Outcomes Using Wearable Actigraphy Device Among End-Stage Cancer Patients.

Survival prediction is highly valued in end-of-life care clinical practice, and patient performance status evaluation stands as a predominant component in survival prognostication. While current performance status evaluation tools are limited to their subjective nature, the advent of wearable technology enables continual recordings of patients' activity and has the potential to measure performance status objectively. We hypothesize that wristband actigraphy monitoring devices can predict in-hospital death of end-stage cancer patients during the time of their hospital admissions. The objective of this study was to train and validate a long short-term memory (LSTM) deep-learning prediction model based on activity data of wearable actigraphy devices. The study recruited 60 end-stage cancer patients in a hospice care unit, with 28 deaths and 32 discharged in stable condition at the end of their hospital stay. The standard Karnofsky Performance Status score had an overall prognostic accuracy of 0.83. The LSTM prediction model based on patients' continual actigraphy monitoring had an overall prognostic accuracy of 0.83. Furthermore, the model performance improved with longer input data length up to 48 h. In conclusion, our research suggests the potential feasibility of wristband actigraphy to predict end-of-life admission outcomes in palliative care for end-stage cancer patients. Clinical Trial Registration: The study protocol was registered on ClinicalTrials.gov (ID: NCT04883879).

Diagnostic Accuracy of Female Pelvic Ultrasonography in Differentiating Precocious Puberty From Premature Thelarche: A Systematic Review and Meta-analysis.

Background: The gonadotropin-releasing hormone (GnRH) stimulation test is the benchmark for diagnosing precocious puberty (PP). However, it is invasive, time-consuming, costly, and may create an unpleasant experience for participants. Moreover, some overlaps may occur between PP and premature thelarche (PT) in the early stage of PP. Female pelvic ultrasonography may provide additional information to help differentiate PP from PT and subsequently initiate early treatment. In this study, we aimed to first directly compare pelvic ultrasonography parameters between PP and PT groups and secondly, investigate their diagnostic accuracy compared with the GnRH stimulation test. Methods: A systematic search of the PubMed/MEDLINE, EMBASE, Scopus, and Cochrane Library databases was performed up to March 31, 2021. All types of studies, except for case reports and review articles, were included. The GnRH stimulation test was used to confirm PP diagnosis. Those whose organic conditions might cause PP were excluded. The mean, standard deviation, sensitivity, and specificity of each parameter were documented. Forest plots were constructed to display the estimated standardized mean differences (SMDs) from each included study and the overall calculations. A bivariate model was used to calculate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Results: A total of 13 studies were included for analysis. The SMDs (95% confidence interval - CI) in ovarian volume, fundal-cervical ratio, uterine length, uterine cross-sectional area, and uterine volume between PP and PT groups were 1.12 (0.78-1.45; p < 0.01), 0.90 (0.07-1.73; p = 0.03), 1.38 (0.99-1.78; p < 0.01), 1.06 (0.61-1.50; p < 0.01), and 1.21 (0.84-1.58; p <0.01), respectively. A uterine length of 3.20 cm yielded a pooled sensitivity of 81.8% (95% CI 78.3%-84.9%), specificity of 82.0% (95% CI 61.0%-93.0%), PLR of 4.56 (95% CI 2.15-9.69), NLR of 0.26 (95% CI 0.17-0.39), and DOR of 19.62 (95% CI 6.45-59.68). The area under the summary receiver operating characteristics curve was 0.82. Conclusion: Female pelvic ultrasonography may serve as a complementary tool to the GnRH stimulation test in differentiating PP from PT. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232427, ID: CRD42021232427.

Detection and Classification of Stroke Gaits by Deep Neural Networks Employing Inertial Measurement Units.

This paper develops Deep Neural Network (DNN) models that can recognize stroke gaits. Stroke patients usually suffer from partial disability and develop abnormal gaits that can vary widely and need targeted treatments. Evaluation of gait patterns is crucial for clinical experts to make decisions about the medication and rehabilitation strategies for the stroke patients. However, the evaluation is often subjective, and different clinicians might have different diagnoses of stroke gait patterns. In addition, some patients may present with mixed neurological gaits. Therefore, we apply artificial intelligence techniques to detect stroke gaits and to classify abnormal gait patterns. First, we collect clinical gait data from eight stroke patients and seven healthy subjects. We then apply these data to develop DNN models that can detect stroke gaits. Finally, we classify four common gait abnormalities seen in stroke patients. The developed models achieve an average accuracy of 99.35% in detecting the stroke gaits and an average accuracy of 97.31% in classifying the gait abnormality. Based on the results, the developed DNN models could help therapists or physicians to diagnose different abnormal gaits and to apply suitable rehabilitation strategies for stroke patients.

Diagnostic Accuracy of Ambulatory Devices in Detecting Atrial Fibrillation: Systematic Review and Meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. Early diagnosis of AF is crucial for preventing AF-related morbidity, mortality, and economic burden, yet the detection of the disease remains challenging. The 12-lead electrocardiogram (ECG) is the gold standard for the diagnosis of AF. Because of technological advances, ambulatory devices may serve as convenient screening tools for AF. OBJECTIVE: The objective of this review was to investigate the diagnostic accuracy of 2 relatively new technologies used in ambulatory devices, non-12-lead ECG and photoplethysmography (PPG), in detecting AF. We performed a meta-analysis to evaluate the diagnostic accuracy of non-12-lead ECG and PPG compared to the reference standard, 12-lead ECG. We also conducted a subgroup analysis to assess the impact of study design and participant recruitment on diagnostic accuracy. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. MEDLINE and EMBASE were systematically searched for articles published from January 1, 2015 to January 23, 2021. A bivariate model was used to pool estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the summary receiver operating curve (SROC) as the main diagnostic measures. Study quality was evaluated using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. RESULTS: Our search resulted in 16 studies using either non-12-lead ECG or PPG for detecting AF, comprising 3217 participants and 7623 assessments. The pooled estimates of sensitivity, specificity, PLR, NLR, and diagnostic odds ratio for the detection of AF were 89.7% (95% CI 83.2%-93.9%), 95.7% (95% CI 92.0%-97.7%), 20.64 (95% CI 10.10-42.15), 0.11 (95% CI 0.06-0.19), and 224.75 (95% CI 70.10-720.56), respectively, for the automatic interpretation of non-12-lead ECG measurements and 94.7% (95% CI 93.3%-95.8%), 97.6% (95% CI 94.5%-99.0%), 35.51 (95% CI 18.19-69.31), 0.05 (95% CI 0.04-0.07), and 730.79 (95% CI 309.33-1726.49), respectively, for the automatic interpretation of PPG measurements. CONCLUSIONS: Both non-12-lead ECG and PPG offered high diagnostic accuracies for AF. Detection employing automatic analysis techniques may serve as a useful preliminary screening tool before administering a gold standard test, which generally requires competent physician analyses. Subgroup analysis indicated variations of sensitivity and specificity between studies that recruited low-risk and high-risk populations, warranting future validity tests in the general population. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42020179937; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179937.

Dexamethasone accelerates muscle regeneration by modulating kinesin-1-mediated focal adhesion signals.

During differentiation, skeletal muscle develops mature multinucleated muscle fibers, which could contract to exert force on a substrate. Muscle dysfunction occurs progressively in patients with muscular dystrophy, leading to a loss of the ability to walk and eventually to death. The synthetic glucocorticoid dexamethasone (Dex) has been used therapeutically to treat muscular dystrophy by an inhibition of inflammation, followed by slowing muscle degeneration and stabilizing muscle strength. Here, in mice with muscle injury, we found that Dex significantly promotes muscle regeneration via promoting kinesin-1 motor activity. Nevertheless, how Dex promotes myogenesis through kinesin-1 motors remains unclear. We found that Dex directly increases kinesin-1 motor activity, which is required for the expression of a myogenic marker (muscle myosin heavy chain 1/2), and also for the process of myoblast fusion and the formation of polarized myotubes. Upon differentiation, kinesin-1 mediates the recruitment of integrin ß1 onto microtubules allowing delivery of the protein into focal adhesions. Integrin ß1-mediated focal adhesion signaling then guides myoblast fusion towards a polarized morphology. By imposing geometric constrains via micropatterns, we have proved that cell adhesion is able to rescue the defects caused by kinesin-1 inhibition during the process of myogenesis. These discoveries reveal a mechanism by which Dex is able to promote myogenesis, and lead us towards approaches that are more efficient in improving skeletal muscle regeneration.

Impact of breath-hold level on positional error aligned by stent/Lipiodol in Hepatobiliary radiotherapy with breath-hold respiratory control.

BACKGROUND: Respiratory motion management with breath hold for patients with hepatobiliary cancers remain a challenge in the precise positioning for radiotherapy. We compared different image-guided alignment markers for estimating positional errors, and investigated the factors associated with positional errors under breath-hold control. METHODS: Spirometric motion management system (SDX) for breath holds was used in 44 patients with hepatobiliary tumor. Among them, 28 patients had a stent or embolized materials (lipiodol) as alignment markers. Cone-beam computed tomography (CBCT) and kV-orthogonal images were compared for accuracy between different alignment references. Breath-hold level (BHL) was practiced, and BHL variation (ΔBHL) was defined as the standard deviation in differences between actual BHLs and baseline BHL. Mean BHL, ΔBHL, and body-related factors were analyzed for the association with positional errors. RESULTS: Using the reference CBCT, the correlations of positional errors were significantly higher in those with stent/lipiodol than when the vertebral bone was used for alignment in three dimensions. Patients with mean BHL > 1.4 L were significantly taller (167.6 cm vs. 161.6 cm, p = 0.03) and heavier (67.1 kg vs. 57.4 kg, p = 0.02), and had different positional error in the craniocaudal direction (- 0.26 cm [caudally] vs. + 0.09 cm [cranially], p = 0.01) than those with mean BHL < 1.4 L. Positional errors were similar for patients with ΔBHL< 0.03 L and > 0.03 L. CONCLUSION: Under rigorous breath-hold respiratory control, BHL correlated with body weight and height. With more accurate alignment reference by stent/lipiodol, actual BHL but not breath-hold variation was associated with craniocaudal positional errors.

Targeting human epidermal growth factor receptor 2 enhances radiosensitivity and reduces the metastatic potential of Lewis lung carcinoma cells.

BACKGROUND: Sublethal radiation induces matrix metalloproteinase 9 (MMP-9)-mediated radioresistance in Lewis lung carcinoma (LLC) cells and their metastatic dissemination. We aim to determine if EGFR/HER2 activation associates with MMP-9-mediated radioresistance and invasiveness in irradiated LLC cells. METHODS: LLC cells were treated with erlotinib or afatinib followed by sublethal radiation. After irradiation, we examined the phosphorylation of EGFR/HER2 and MMP-9 expression. Colony formation assay determined if the kinase inhibitors sensitize LLC cells to radiation. Matrigel-coated Boyden chamber assay assessed cellular invasiveness. Resulting tumors of wild-type LLC cells or HER2 knock-down mutant cells were irradiated to induce pulmonary metastases. RESULTS: Afatinib more effectively sensitized LLC cells to radiation and decreased invasiveness by inhibiting phosphorylation of EGFR, HER2, Akt, ERK, and p38, and down-regulating MMP-9 when compared to erlotinib. Afatinib abolished radiation-induced lung metastases in vivo. Furthermore, LLC HER2 knock-down cells treated with radiation had growth inhibition. CONCLUSION: Dual inhibition of radiation-activated EGFR and HER2 signaling by afatinib suppressed the proliferation and invasion of irradiated LLC cells. Increased radiosensitivity and decreased metastatic dissemination were observed by pharmacological or genetic HER2 inhibition in vivo. These findings indicate that HER2 plays a pivotal role in enhancing radioresistance and reducing metastatic potential of LLC cells.