Neurosyphilis Initially Misdiagnosed as Behavioral Variant Frontotemporal Dementia: Life-Changing Differential Diagnosis.

Diagnosing neurosyphilis can be challenging and it may be misdiagnosed as behavior variant frontotemporal dementia, given its affinity for the frontal and temporal lobes. Here we present a model case, who, in his 40 s, was initially misdiagnosed with behavioral variant frontotemporal dementia based on extreme self-neglect and disinhibition over six months and frontal lobe atrophy. He was later diagnosed as neurosyphilis with positive syphilis tests in his cerebrospinal fluid. He underwent penicillin treatment and fully recovered. Relatively rapid cognitive decline, particularly if young, should prompt physicians to consider neurosyphilis as a treatable dementia, which could completely change a patient's life.

Shadowing Behavior May Be Associated with an Inability to Recognize the External World: A Case Report of Shadowing in a Patient with Posterior Cortical Atrophy.

Although shadowing behavior- when one individual closely follows another- is routinely documented among patients with dementia, its mechanisms have yet to be elucidated. In particular, there have been no detailed descriptions of patients with shadowing behavior. To propose its potential backgrounds, we describe a patient with posterior cortical atrophy who exhibited prominent shadowing behavior. He also experienced severe difficulties recognizing external stimuli, including visuospatial dysfunction, several types of agnosia, difficulties in verbal comprehension, disorientation, and its associated depression. This shadowing behavior may be adaptive relative to his extreme difficulty with recognizing the world around him.

Pneumonia Risk Increased by Dementia-Related Daily Living Difficulties: Poor Oral Hygiene and Dysphagia as Contributing Factors.

OBJECTIVE: Although pneumonia is the leading cause of death among patients with dementia, the specific underlying causes remain unclear. In particular, the potential connection between pneumonia risk and dementia-related daily living difficulties, such as oral hygiene practice and mobility impairment, and the use of physical restraint as a management practice, has not been extensively studied. METHODS: In our retrospective study, we included 454 admissions corresponding to 336 individual patients with dementia who were admitted to a neuropsychiatric unit due to behavioral and psychological symptoms. The admissions were divided into two groups: those who developed pneumonia while hospitalized (n=62) and those who did not (n=392). We investigated differences between the two groups in terms of dementia etiology, dementia severity, physical conditions, medical complications, medication, dementia-related difficulties in daily living, and physical restraint. To control potential confounding variables, we used mixed effects logistic regression analysis to identify risk factors for pneumonia in this cohort. RESULTS: Our study found that the development of pneumonia in patients with dementia was associated with poor oral hygiene, dysphagia, and loss of consciousness. Physical restraint and mobility impairment showed a weaker, nonsignificant association with the development of pneumonia. CONCLUSIONS: Our findings suggest that pneumonia in this population may be caused by two primary factors: increased pathogenic microorganisms in the oral cavity due to poor hygiene, and an inability to clear aspirated contents due to dysphagia and loss of consciousness. Further investigation is needed to clarify the relationship between physical restraint, mobility impairment, and pneumonia in this population.

Clinical characteristics and potential association to Parkinson's disease and dementia with Lewy bodies in patients with major depressive disorder who received maintenance electroconvulsive therapy: a retrospective chart review study.

BACKGROUND: Maintaining remission after electroconvulsive therapy (ECT) is clinically relevant in patients with depression, and maintenance ECT has been introduced in patients who fail to maintain remission after ECT. However, the clinical characteristics and biological background of patients who receive maintenance ECT are poorly understood. Thus, this study aimed to examine the clinical background of patients who underwent maintenance ECT. METHODS: Patients with major depressive disorder who underwent ECT followed by maintenance ECT (mECT group) and those who did not (acute ECT [aECT] group) were included. Clinical characteristics, including the results of neuroimaging examinations for Parkinson's disease (PD) and dementia with Levy body (DLB) such as myocardial 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter imaging single-photon emission computerized tomography (DaT-SPECT), were compared between the groups. RESULTS: In total, 13 and 146 patients were included in the mECT and aECT groups, respectively. Compared to the aECT group, the mECT group showed a significantly higher prevalence of melancholic features (92.3% vs. 27.4%, p < 0.001) and catatonic features (46.2% vs. 9.6%, p = 0.002). Overall, 8 of the 13 patients in the mECT group and 22 of the 146 patients in the aECT group underwent neuroimaging examinations for PD/DLB. The rate of patients examined is significantly higher in the mECT group than in the aECT group (61.5% vs. 11.2%, p < 0.001). Among the groups examined, 7/8 patients in the mECT group and 16/22 patients in the aECT group showed relevant neuroimaging findings for PD/DLB; the positive rate was not significantly different between the two groups (87.5% vs. 72.7%, p = 0.638). CONCLUSIONS: Patients who receive acute and maintenance ECT may have underlying neurodegenerative diseases, including PD/DLB. Investigating the neurobiology of patients who receive maintenance ECT is important for developing appropriate treatments for depression.

Caution to psychiatry ward: COVID-19 pneumonia can manifest weeks or months after testing positive with a PCR test in individuals on preexisting immune-suppressing medication.

Background: Some patients are reported to develop depression immediately after COVID-19 infection. Typically, hospitalization is arranged a week to 10 days after symptom onset to avoid outbreak in the psychiatric ward when infectivity is almost eliminated. However, in patients on immunosuppressive drugs, infection is known to persist beyond the 10th day after testing positive with a polymerase chain reaction (PCR) test. Case Presentation: We present a patient with follicular lymphoma who was receiving immune-suppressing medication and contracted a COVID-19 infection; she developed severe depression and eventually required hospitalization 10 days after symptom onset or 5 days after the COVID-19 infection-related symptoms disappeared. Although the patient did not exhibit any symptom of pneumonia upon admission, she developed COVID-19 pneumonia 3 weeks after the initial positive test. She received intravenous infusion of the antiviral drug remdesivir, which led to the improvement of pneumonia, and she was discharged on day 32 from testing COVID-19 positive. However, COVID-19 pneumonia recurred on days 64 and 74. Conclusion: This is the first report of COVID-19 pneumonia developing in a psychiatric ward in a patient on immunosuppressive drugs, weeks to months after testing positive with a PCR test. When patients with compromised immune function, such as those on immunosuppressant medication or those with human immunodeficiency virus disease, are admitted to a psychiatric ward, careful monitoring of the risk of recurrence and sufficient consideration for infection control measures are necessary to avoid outbreaks.

[Bone Marrow Carcinomatosis with Disseminated Intravascular Coagulation in a Breast Cancer Patient Treated with Chemotherapy and CDK4/6 Inhibitor].

We report a case of a breast cancer patient with bone marrow carcinomatosis and disseminated intravascular coagulation who was treated with chemotherapy and a CDK4/6 inhibitor. The patients, a 68-year-old woman, presented to our hospital with anorexia and was found to have multiple liver metastases of breast cancer. Furthermore, she had anemia and thrombocytopenia, and a bone marrow biopsy showed bone metastasis of the breast cancer. Therefore, a diagnosis of bone marrow carcinomatosis and disseminated intravascular coagulation was made. Treatment was started with chemotherapy(epirubicin and cyclophosphamide)and subsequently changed to an aromatase inhibitor(letrozole)and a CDK4/4 inhibitor(abemaciclib) and was maintained without exacerbation of the patient's condition.

Individual Prediction of Remission Based on Clinical Features Following Electroconvulsive Therapy: A Machine Learning Approach.

Objective: Previous prediction models for electroconvulsive therapy (ECT) responses have predominantly been based on neuroimaging data, which has precluded widespread application for severe cases in real-world clinical settings. The aims of this study were (1) to build a clinically useful prediction model for ECT remission based solely on clinical information and (2) to identify influential features in the prediction model.Methods: We conducted a retrospective chart review to collect data (registered between April 2012 and March 2019) from individuals with depression (unipolar major depressive disorder or bipolar disorder) diagnosed via DSM-IV-TR criteria who received ECT at Keio University Hospital. Clinical characteristics were used as candidate features. A light gradient boosting machine was used for prediction, and 5-fold cross-validation was performed to validate our prediction model.Results: In total, 177 patients with depression underwent ECT during the study period. The remission rate was 63%. Our model predicted individual patient outcomes with 71% accuracy (sensitivity, 86%; specificity, 46%). A shorter duration of the current episodes, lower baseline severity, higher dose of antidepressant medications before ECT, and lower body mass index were identified as important features for predicting remission following ECT.Conclusions: We developed a prediction model for ECT remission based solely on clinical information. Our prediction model demonstrated accuracy comparable to that in previous reports. Our model suggests that introducing ECT earlier in the treatment course may contribute to improvements in clinical outcomes.

Impact of Sevoflurane and Thiopental Used Over the Course of Electroconvulsive Therapy: Propensity Score Matching Analysis.

Objective: Although anesthetics play an important role in electroconvulsive therapy (ECT), the clinical efficacy and seizure adequacy of sevoflurane in the course of ECT remain unclear. The purpose of this study was to examine the clinical efficacy and seizure adequacy of sevoflurane, compared with those of thiopental, in the course of ECT in patients with mood disorders. Methods: We conducted a retrospective chart review. Patients who underwent a course of ECT and received sevoflurane (n = 26) or thiopental (n = 26) were included. Factors associated with ECT and treatment outcomes were compared between the two groups using propensity score (PS) matching. Between-group differences were examined using an independent t-test for continuous variables and a χ2-test for categorical variables. Results: Patients who received sevoflurane needed more stimulations (sevoflurane: 13.2 ± 4 times, thiopental: 10.0 ± 2.5 times, df = 51, p = 0.001) and sessions (sevoflurane: 10.0 ± 2.1 times, thiopental: 8.4 ± 2.1 times, df = 51, p = 0.01) and had more inadequate seizures (sevoflurane: 5 ± 3.9 times, thiopental: 2.7 ± 2.7 times, df = 51, p = 0.015). Remission and response rates were similar in both groups. Conclusion: The present findings indicate that sevoflurane should be used with caution in ECT and only when the clinical rationale is clear.

Restrictive type and infectious complications might predict nadir hematological values among individuals with anorexia nervosa during the refeeding period: a retrospective study.

BACKGROUND: Although hematological abnormalities in patients with anorexia nervosa have been documented, the mechanisms involved have not been fully clarified, especially during the refeeding period when hematological values further decrease after admission prior to improving. Here we address potential mechanisms underlying the hematological abnormalities of inpatients with anorexia nervosa during the refeeding period. METHODS: We recruited patients from 101 admissions corresponding to 55 individual patients with anorexia nervosa with severe malnutrition (body mass index, 13.4 ± 3.4) from the neuropsychiatry unit in Ashikaga Red Cross Hospital during the period from October 1999 to March 2018. We analyzed three hematological cell measures, i.e., hemoglobin, white cell count, and platelet count, to determine their levels at admission and their lowest levels during the refeeding period and calculated the percent decrease in those values from admission to the nadir levels. We analyzed each measure using a general mixed model with explanatory variables, including data upon admission and a treatment-related indicator, i.e., energy intake. RESULTS: The initial hemoglobin value of 12.1 ± 2.7 g/dl decreased by 22.3% to 9.4 ± 2.5 g/dl; the initial white cell count was 5387 ± 3474/µl, which decreased by 33.6% to 3576 ± 1440/µl; the initial platelet count of 226 ± 101 × 103/µl decreased by 24.3% to 171 ± 80 × 103/µl. All nadir levels were observed during the refeeding period from the fifth to tenth day of hospitalization. Significant correlations among the three hematological cell measures, particularly at the nadir levels, were found. Of note, 41.7% of our patients who received red blood cell transfusion during hospitalization showed normal hemoglobin levels upon admission. The anorexia nervosa restrictive type was associated with a lower nadir level of white blood cell count. Infectious complications were related to a lower nadir level of hemoglobin and a greater percent decrease in hemoglobin level as well as to the need for red blood cell transfusion. CONCLUSIONS: Nadir hematological cell measures of inpatients with anorexia nervosa might be predicted by the restrictive type and infectious complications. The anorexia nervosa restrictive type was associated with further decrease in hematological values during the refeeding period.

Deficiencies in components of the blood, such as a low red blood cell count, low white blood cell count, and low platelet numbers, are observed frequently in patients with anorexia nervosa, particularly those with severe malnutrition, and these deficiencies become manifest after hospitalization during the initial period when patients are reintroduced to food. Why this deterioration occurs even under medical care is not well understood. Here we analyzed the patient factors associated with these blood cell abnormalities. Patients with the restrictive type of anorexia nervosa, and infectious complications were more likely to have the lowest levels of hematological values during the refeeding period.

Differentiating autoimmune encephalitis from schizophrenia spectrum disorders among patients with first-episode psychosis.

BACKGROUND: Although differential diagnosis between autoimmune encephalitis and schizophrenia spectrum disorders is crucial for a good outcome, the psychiatric symptoms that distinguish these two conditions have not been identified even though psychiatric symptoms are often the main manifestation of autoimmune encephalitis. Also, there are many situations in clinical psychiatry in which laboratory testing and imaging studies are not available. Because no comparative study of the psychiatric symptoms between these two conditions has been carried out, we explored diagnostically useful psychiatric symptoms in a retrospective case-control study. METHODS: We recruited 187 inpatients with first-episode psychosis who were admitted to our psychiatric unit and categorized them into two groups: the autoimmune encephalitis group (n = 10) and the schizophrenia spectrum disorders group (n = 177). Differences in the symptoms and signs between the two groups were investigated. RESULTS: Schneider's first-rank symptoms (e.g., verbal commenting hallucinations and delusional self-experience) were observed only in the schizophrenia spectrum disorders group, whereas altered perception was found more frequently in the autoimmune encephalitis group. Functional status was worse in the autoimmune encephalitis group, and neurological and neuropsychological signs were revealed almost exclusively in this group. A history of mental illness was more frequently reported in the schizophrenia spectrum disorders group than in the autoimmune encephalitis group. CONCLUSIONS: The psychiatric symptoms, i.e., Schneider's first-rank symptoms and altered perception, together with neurological and neuropsychological signs, functional status, and past history, may help clinicians accurately differentiate these two conditions among patients with first-episode psychosis.

Symptom changes in patients with pre-existing psychiatric disorders in the initial phase of the COVID-19 pandemic: Vulnerability of female patients and patients with mood disorders.

How patients with pre-existing psychiatric disorders are responding to the COVID-19 pandemic remains unclear, and no comprehensive studies have yet been performed. To elucidate (1) which psychiatric disorders were exacerbated during the initial phase of the COVID-19 pandemic and (2) the contributing factors, we prospectively assessed psychiatric symptoms of 1592 psychiatric outpatients in a single-center study using the Global Assessment of Functioning (GAF) before the state of emergency was declared in Japan and during two months under the state of emergency (study period: April 8 to June 7, 2020). We conducted a chi-squared test for the relationship between psychiatric diagnostic category (ICD-10) and exacerbation. To control for confounders, we conducted a logistic regression analysis using sex, age, diagnostic category, and pre-pandemic GAF score as independent variables. Exacerbation rates of patients with mood disorders (F3) and neurotic disorders (F4) were 4.32% and 5.37%, respectively, and were significantly higher than those for patients with organic disorders (F0) and schizophrenic disorders (F2) (X2 (9, N = 1592) = 27.8, p < .01). Logistic regression analysis revealed that patients with F3 and female patients were significantly more affected than patients with other disorders or male patients, respectively (odds ratio (95% confidence interval) = 2.4 (1.2-4.6), p < .01 for F3; 3.1 (1.5-6.6), p < .01 for females). These findings suggest a need for careful management of patients with mood disorders and female psychiatric patients during a pandemic.

Unobtrusive Sensing Technology for Quantifying Stress and Well-Being Using Pulse, Speech, Body Motion, and Electrodermal Data in a Workplace Setting: Study Concept and Design.

Introduction: Mental disorders are a leading cause of disability worldwide. Depression has a significant impact in the field of occupational health because it is particularly prevalent during working age. On the other hand, there are a growing number of studies on the relationship between "well-being" and employee productivity. To promote healthy and productive workplaces, this study aims to develop a technique to quantify stress and well-being in a way that does not disturb the workplace. Methods and analysis: This is a single-arm prospective observational study. The target population is adult (>20 years old) workers at companies that often engage in desk work; specifically, a person who sits in front of a computer for at least half their work hours. The following data will be collected: (a) participants' background characteristics; (b) participants' biological data during the 4-week observation period using sensing devices such as a camera built into the computer (pulse wave data extracted from the facial video images), a microphone built into their work computer (voice data), and a wristband-type wearable device (electrodermal activity data, body motion data, and body temperature); (c) stress, well-being, and depression rating scale assessment data. The analysis workflow is as follows: (1) primary analysis, comprised of using software to digitalize participants' vital information; (2) secondary analysis, comprised of examining the relationship between the quantified vital data from (1), stress, well-being, and depression; (3) tertiary analysis, comprised of generating machine learning algorithms to estimate stress, well-being, and degree of depression in relation to each set of vital data as well as multimodal vital data. Discussion: This study will evaluate digital phenotype regarding stress and well-being of white-collar workers over a 4-week period using persistently obtainable biomarkers such as heart rate, acoustic characteristics, body motion, and electrodermal activity. Eventually, this study will lead to the development of a machine learning algorithm to determine people's optimal levels of stress and well-being. Ethics and dissemination: Collected data and study results will be disseminated widely through conference presentations, journal publications, and/or mass media. The summarized results of our overall analysis will be supplied to participants. Registration: UMIN000036814.

[A Case of Palbociclib plus Fulvestrant‒Resistant Metastatic Breast Cancer That Responded to Abemaciclib plus Fulvestrant].

We report the case of a 72‒year‒old woman with ER(+), PgR(+), HER2(-)metastatic breast cancer with liver involvement. The patient received palbociclib(125 mg daily po 3 weeks on/1 week off)and fulvestrant(500 mg im on days 1, 15, and 29, and once monthly thereafter)as second‒line endocrine therapy. Her metastatic liver lesions initially decreased in size and the tumor‒marker CA15‒3 level decreased. However, they progressed after seven months of therapy. She was subsequently switched to abemaciclib(150 mg twice/daily po)with fulvestrant as third‒line therapy, resulting in a decrease in the same liver lesions. She has continued treatment for 12 months. Based on this case, abemaciclib may be clinically useful for breast cancer that is not responsive or has become resistant to palbociclib, another selective CDK4/6 inhibitor.

Electroconvulsive Therapy for Patients With Depression Who Lack Capacity for Consent: Doing Good and Doing No Harm.

OBJECTIVE: Electroconvulsive therapy (ECT) is provided in real-world clinical settings for patients lacking capacity for consent. The aim of this study was to investigate the clinical characteristics and clinical effectiveness of ECT in this population. METHODS: A retrospective chart review was conducted to collect data from patients who received ECT to treat their depressive episodes between April 2012 and March 2019. Differences in clinical characteristics and short-/long-term clinical outcomes between patients who received ECT with their relatives' consent and patients who received ECT by their own consent were examined. The short-/long-term clinical outcomes were determined by clinical global impression scores and readmission rate, respectively. RESULTS: Of 168 patients with depressive episodes, 34 (20.2%) received ECT with their relatives' consent. Those patients were older, had lower body mass index, and had shorter episode duration. They also exhibited more frequent psychotic, melancholic, and catatonic features. The main indication for ECT in this population was the need for rapid recovery. Patients lacking capacity for consent showed similar remission (61.8%) and response (82.4%) rates to those with capacity for consent. Readmission rate was not significantly different between groups. CONCLUSIONS: There were no significant differences in short-/long-term ECT effectiveness between patients with/without capacity for consent. Electroconvulsive therapy is the only established and effective treatment in clinical settings for the most severe cases, wherein patients are incapable of giving consent but need rapid recovery. A general rejection of this practice due to concerns surrounding consent may be unethical under the ethical principles of medical care.

"Case series: ischemic stroke associated with dehydration and arteriosclerosis in individuals with severe anorexia nervosa".

BACKGROUND: Numerous reports have indicated that patients with anorexia nervosa (AN) are at a relatively high risk of developing vascular diseases, including cardiovascular events and venous thromboembolism. However, there have been no previous reports of the development of ischemic stroke during refeeding therapy in patients with severe AN. This report is aimed at reporting the characteristics of an ischemic stroke in patients with AN. CASE PRESENTATIONS: Our study included 29 admissions by independent 19 female patients cases (19 patients), who received thorough medical, neurological, and psychiatric examinations. Two patients were diagnosed as having developed ischemic stroke; the first patient showed multiple infarctions in the brain, while the second showed symptomatic focal infarction. Our findings suggest that dehydration and arteriosclerosis, in association with severe malnutrition, could predispose to the development of ischemic stroke in patients with severe AN. CONCLUSIONS: Development of ischemic stroke in patients with AN might be overlooked. Watching out for neurological signs would help in early diagnosis of ischemic stroke in patients with AN during refeeding. Specific etiology could induce ischemic stroke in patients with AN even if they have no common risk factors of ischemia.

Electroconvulsive Therapy for Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Electroconvulsive therapy (ECT) is a well-established treatment for psychiatric disorders, including depression and psychosis. ECT has been reported to be effective in treating such psychiatric symptoms in patients with Parkinson's disease (PD) and has been also reported to be effective in treating motor symptoms. The aim of the study is to summarize previous clinical studies investigating the efficacy of ECT for symptoms in patients with PD. METHODS: A systematic review and meta-analysis of any study designs assessing motor and/or non-motor symptoms in patients with PD before and after ECT. Co-primary outcomes were set as motor manifestations assessed using the Unified Parkinson's Disease Rating Scale or other rating scales, and non-motor symptoms included depression and psychosis. Secondary outcomes were wearing-off phenomenon and cognitive function. The impact of ECT on those symptoms was examined by comparing the severity of the symptoms before and after ECT using a random effect model and was expressed in standardized mean difference. RESULTS: Of 1219 identified citations, 14 studies (n = 129; 1 randomized controlled study, 9 prospective observational studies, and 4 retrospective studies) were analyzed. The findings were as follows: ECT significantly improved motor manifestations in patients with PD, and the improvement was significant in the subpopulation without psychiatric symptoms; ECT significantly improved depression and psychosis; and ECT significantly relieved wearing-off phenomenon and did not worsen cognitive functioning. CONCLUSION: The current meta-analysis suggests the potential benefit of ECT on motor and non-motor symptoms in presumably complicated and difficult-to-treat subgroups. © 2020 International Parkinson and Movement Disorder Society.

Virtual reality exposure therapy for social anxiety disorder: a systematic review and meta-analysis.

BACKGROUND: Virtual reality exposure therapy (VRET) is currently being used to treat social anxiety disorder (SAD); however, VRET's magnitude of efficacy, duration of efficacy, and impact on treatment discontinuation are still unclear. METHODS: We conducted a meta-analysis of studies that investigated the efficacy of VRET for SAD. The search strategy and analysis method are registered at PROSPERO (#CRD42019121097). Inclusion criteria were: (1) studies that targeted patients with SAD or related phobias; (2) studies where VRET was conducted for at least three sessions; (3) studies that included at least 10 participants. The primary outcome was social anxiety evaluation score change. Hedges' g and its 95% confidence intervals were calculated using random-effect models. The secondary outcome was the risk ratio for treatment discontinuation. RESULTS: Twenty-two studies (n = 703) met the inclusion criteria and were analyzed. The efficacy of VRET for SAD was significant and continued over a long-term follow-up period: Hedges' g for effect size at post-intervention, -0.86 (-1.04 to -0.68); three months post-intervention, -1.03 (-1.35 to -0.72); 6 months post-intervention, -1.14 (-1.39 to -0.89); and 12 months post-intervention, -0.74 (-1.05 to -0.43). When compared to in vivo exposure, the efficacy of VRET was similar at post-intervention but became inferior at later follow-up points. Participant dropout rates showed no significant difference compared to in vivo exposure. CONCLUSION: VRET is an acceptable treatment for SAD patients that has significant, long-lasting efficacy, although it is possible that during long-term follow-up, VRET efficacy lessens as compared to in vivo exposure.

Small GTP-Binding Protein GDP Dissociation Stimulator Prevents Thoracic Aortic Aneurysm Formation and Rupture by Phenotypic Preservation of Aortic Smooth Muscle Cells.

BACKGROUND: Thoracic aortic aneurysm (TAA) and dissection are fatal diseases that cause aortic rupture and sudden death. The small GTP-binding protein GDP dissociation stimulator (SmgGDS) is a crucial mediator of the pleiotropic effects of statins. Previous studies revealed that reduced force generation in aortic smooth muscle cells (AoSMCs) causes TAA and thoracic aortic dissection. METHODS: To examine the role of SmgGDS in TAA formation, we used an angiotensin II (1000 ng·min-1·kg-1, 4 weeks)-induced TAA model. RESULTS: We found that 33% of Apoe-/- SmgGDS+/- mice died suddenly as a result of TAA rupture, whereas there was no TAA rupture in Apoe-/- control mice. In contrast, there was no significant difference in the ratio of abdominal aortic aneurysm rupture between the 2 genotypes. We performed ultrasound imaging every week to follow up the serial changes in aortic diameters. The diameter of the ascending aorta progressively increased in Apoe-/- SmgGDS+/- mice compared with Apoe-/- mice, whereas that of the abdominal aorta remained comparable between the 2 genotypes. Histological analysis of Apoe-/- SmgGDS+/- mice showed dissections of major thoracic aorta in the early phase of angiotensin II infusion (day 3 to 5) and more severe elastin degradation compared with Apoe-/- mice. Mechanistically, Apoe-/- SmgGDS+/- mice showed significantly higher levels of oxidative stress, matrix metalloproteinases, and inflammatory cell migration in the ascending aorta compared with Apoe-/- mice. For mechanistic analyses, we primary cultured AoSMCs from the 2 genotypes. After angiotensin II (100 nmol/L) treatment for 24 hours, Apoe-/- SmgGDS+/- AoSMCs showed significantly increased matrix metalloproteinase activity and oxidative stress levels compared with Apoe-/- AoSMCs. In addition, SmgGDS deficiency increased cytokines/chemokines and growth factors in AoSMCs. Moreover, expressions of fibrillin-1 ( FBN1), α-smooth muscle actin ( ACTA2), myosin-11 ( MYH11), MYLLK, and PRKG1, which are force generation genes, were significantly reduced in Apoe-/- SmgGDS+/- AoSMCs compared with Apoe-/- AoSMCs. A similar tendency was noted in AoSMCs from patients with TAA compared with those from control subjects. Finally, local delivery of the SmgGDS gene construct reversed the dilation of the ascending aorta in Apoe-/- SmgGDS+/- mice. CONCLUSIONS: These results suggest that SmgGDS is a novel therapeutic target for the prevention and treatment of TAA.