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Traumatic Brain Injury (TBI) presents a broad spectrum of clinical presentations and outcomes due to its inherent heterogeneity, leading to diverse recovery trajectories and varied therapeutic responses. While many studies have delved into TBI phenotyping for distinct patient populations, identifying TBI phenotypes that consistently generalize across various settings and populations remains a critical research gap. Our research addresses this by employing multivariate time-series clustering to unveil TBI's dynamic intricates. Utilizing a self-supervised learning-based approach to clustering multivariate time-Series data with missing values (SLAC-Time), we analyzed both the research-centric TRACK-TBI and the real-world MIMIC-IV datasets. Remarkably, the optimal hyperparameters of SLAC-Time and the ideal number of clusters remained consistent across these datasets, underscoring SLAC-Time's stability across heterogeneous datasets. Our analysis revealed three generalizable TBI phenotypes (α, ß, and γ), each exhibiting distinct non-temporal features during emergency department visits, and temporal feature profiles throughout ICU stays. Specifically, phenotype α represents mild TBI with a remarkably consistent clinical presentation. In contrast, phenotype ß signifies severe TBI with diverse clinical manifestations, and phenotype γ represents a moderate TBI profile in terms of severity and clinical diversity. Age is a significant determinant of TBI outcomes, with older cohorts recording higher mortality rates. Importantly, while certain features varied by age, the core characteristics of TBI manifestations tied to each phenotype remain consistent across diverse populations.
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Oral cancer is a malignant neoplasia that can originate in the oral cavity or lips. It is a serious global health problem and one of the ten most common cancers worldwide. Over the years, changes in the trends of the oral cavity and oropharyngeal cancers have been observed. The management of oral cancer is complicated due to the functional and cosmetic consequences of treating malignancies at these anatomical locations. The tumor and its treatment can affect a variety of functional activities, including smell, sight, speaking, respiration, taste, jaw function, and mastication, either temporarily or permanently. Based on the importance of this tumor, screening oral cancer for early detection and finding the best biomarkers for diagnosis is a crucial concern. In this review of literature, the etiology, risk factors, treatment, and diagnosis of oral cancer will be reviewed with a focus on the most important biomarkers.
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Traumatic Brain Injury (TBI) presents a broad spectrum of clinical presentations and outcomes due to its inherent heterogeneity, leading to diverse recovery trajectories and varied therapeutic responses. While many studies have delved into TBI phenotyping for distinct patient populations, identifying TBI phenotypes that consistently generalize across various settings and populations remains a critical research gap. Our research addresses this by employing multivariate time-series clustering to unveil TBI's dynamic intricates. Utilizing a self-supervised learning-based approach to clustering multivariate time-Series data with missing values (SLAC-Time), we analyzed both the research-centric TRACK-TBI and the real-world MIMIC-IV datasets. Remarkably, the optimal hyperparameters of SLAC-Time and the ideal number of clusters remained consistent across these datasets, underscoring SLAC-Time's stability across heterogeneous datasets. Our analysis revealed three generalizable TBI phenotypes (α, ß, and γ), each exhibiting distinct non-temporal features during emergency department visits, and temporal feature profiles throughout ICU stays. Specifically, phenotype α represents mild TBI with a remarkably consistent clinical presentation. In contrast, phenotype ß signifies severe TBI with diverse clinical manifestations, and phenotype γ represents a moderate TBI profile in terms of severity and clinical diversity. Age is a significant determinant of TBI outcomes, with older cohorts recording higher mortality rates. Importantly, while certain features varied by age, the core characteristics of TBI manifestations tied to each phenotype remain consistent across diverse populations.
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Background: Tumor-infiltrating lymphocytes (TILs) and brain stromal cells produce immunosuppressive cytokines, contributing to an immunosuppressive tumor microenvironment (TME). Interleukin-38 (IL-38) is a novel anti-inflammatory cytokine and a natural modulator of the innate and adaptive immune system. However, its biological roles in brain tumors are not well defined. Objective: To assess the serum levels of IL-38 and the percentages of TILs in the tumor tissues of patients with primary brain tumors and to determine their associations with the pathological features of the disease. Methods: IL-38 was evaluated in sera using the enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (H&E)-stained sections were scored to determine the percentages of TILs in four different areas: the invasive margin, central tumor, perivascular and perinecrotic areas. Results: IL-38 serum levels were significantly higher in low- and high-grade tumors than in healthy individuals, meanwhile, its levels remained consistent between these two grades. Although no significant difference was found in IL-38 serum levels between different histological subtypes of brain tumors, its levels were significantly higher in intra-axial brain tumors than in extra-axial ones. Additionally, a significant positive correlation was observed between serum levels of IL-38 and tumor size in patients with low-grade tumors. TILs were detected in at least one of the four examined areas; however, no statistically significant correlation was found between IL-38 levels and TILs. Conclusion: Our data may suggest a connection between IL-38 and immune suppression and tumor progression in primary brain tumors. Further investigation is needed to uncover the role of IL-38 in the brain tumor microenvironment.
Subject(s)
Brain Neoplasms , Interleukins , Lymphocytes, Tumor-Infiltrating , Humans , Brain Neoplasms/metabolism , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Prognosis , Tumor MicroenvironmentABSTRACT
BACKGROUND: The end of 2019 marked the emergence of the COVID-19 pandemic. Public avoidance of health care facilities, including the emergency department (ED), has been noted during prior pandemics. OBJECTIVE: This study described pandemic-related changes in adult and pediatric ED presentations, acuity, and hospitalization rates during the pandemic in a major metropolitan area. METHODS: The study was a cross-sectional analysis of ED visits occurring before and during the pandemic. Sites collected daily ED patient census; monthly ED patient acuity, as the Emergency Severity Index (ESI) score; and disposition. Prepandemic ED visits occurring from January 1, 2019 through December 31, 2019 were compared with ED visits occurring during the pandemic from January 1, 2020 through March 31, 2021. The change in prepandemic and pandemic ED volume was found using 7-day moving average of proportions. RESULTS: The study enrolled 83.8% of the total ED encounters. Pandemic adult and pediatric visit volume decreased to as low as 44.7% (95% CI 43.1-46.3%; p < 0.001) and 22.1% (95% CI 19.3-26.0%; p < 0.001), respectively, of prepandemic volumes. There was also a relative increase in adult and pediatric acuity (ESI level 1-3) and the admission percentage for adult (20.3% vs. 22.9%; p < 0.01) and pediatric (5.1% vs. 5.6%; p < 0.01) populations. CONCLUSIONS: Total adult and pediatric encounters were reduced significantly across a major metropolitan area. Patient acuity and hospitalization rates were relatively increased. The development of strategies for predicting ED avoidance will be important in future pandemics.
Subject(s)
COVID-19 , Adult , Humans , Child , COVID-19/epidemiology , Pandemics , Cross-Sectional Studies , Retrospective Studies , Emergency Service, HospitalABSTRACT
Aims: Salivary gland tumors (SGTs) are a rare and diverse group of tumors that account for 3 to 10% of all head and neck malignancies. We aimed to conduct a comprehensive epidemiological analysis of SGTs in the south of Iran and compare the findings with previous reports from Iran and other parts of the world. Methods: Using a retrospective study, 405 patients diagnosed with SGTs were observed over an eight-year period between April 2013 and October 2021 in Shiraz, Iran. Patients' demographic and clinicopathological features were obtained from patients' records. Quantitative and descriptive data analysis was performed using SPSS software. Results: There were 302 benign (74.5%) and 103 (25.4%) malignant SGTs. Pleomorphic adenoma and Warthin's tumors were the most common benign SGTs (70.5% and 21.5%, respectively). The most common malignant SGTs were mucoepidermoid carcinoma and adenoid cystic carcinoma (26.2% and 22.3%, respectively). There was a statistically significant association between tumor origin and its malignancy status (p < 0.001). In addition, the results indicated that benign tumors were most commonly detected in the parotid gland (p < 0.05). The benign tumors were more frequently observed among the younger population (p = 0.006). Conclusion: In summary, the findings of the current study were mainly consistent with the previous reports from Iran and the rest of the world. Benign tumors were the most prevalent type of SGTs, and the parotid gland was the most common site. While the majority of cases that developed from the major salivary glands were benign, all the minor SGTs were malignant. Older patients were more likely to develop malignant tumors compared to younger ones. This study provides insights into the prevalence, age-related incidence, gender distribution, and geographic variation of salivary gland tumors. This can be instrumental to develop a guideline for screening, diagnosis, and determining an optimal treatment.
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Self-supervised learning approaches provide a promising direction for clustering multivariate time-series data. However, real-world time-series data often include missing values, and the existing approaches require imputing missing values before clustering, which may cause extensive computations and noise and result in invalid interpretations. To address these challenges, we present a Self-supervised Learning-based Approach to Clustering multivariate Time-series data with missing values (SLAC-Time). SLAC-Time is a Transformer-based clustering method that uses time-series forecasting as a proxy task for leveraging unlabeled data and learning more robust time-series representations. This method jointly learns the neural network parameters and the cluster assignments of the learned representations. It iteratively clusters the learned representations with the K-means method and then utilizes the subsequent cluster assignments as pseudo-labels to update the model parameters. To evaluate our proposed approach, we applied it to clustering and phenotyping Traumatic Brain Injury (TBI) patients in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study. Clinical data associated with TBI patients are often measured over time and represented as time-series variables characterized by missing values and irregular time intervals. Our experiments demonstrate that SLAC-Time outperforms the baseline K-means clustering algorithm in terms of silhouette coefficient, Calinski Harabasz index, Dunn index, and Davies Bouldin index. We identified three TBI phenotypes that are distinct from one another in terms of clinically significant variables as well as clinical outcomes, including the Extended Glasgow Outcome Scale (GOSE) score, Intensive Care Unit (ICU) length of stay, and mortality rate. The experiments show that the TBI phenotypes identified by SLAC-Time can be potentially used for developing targeted clinical trials and therapeutic strategies.
Subject(s)
Brain Injuries, Traumatic , Humans , Brain Injuries, Traumatic/diagnosis , Cluster Analysis , Time Factors , Intensive Care Units , Supervised Machine LearningABSTRACT
Salivary glands naturally play central roles in oral immunity. The salivary glands microenvironment inevitable may be exposed to exogenous factors consequently triggering the initiation and formation of various malignant and benign tumors. Mesenchymal stem cells are recruited into salivary gland microenvironment, interact with tumor cells, and induce inhibitory cytokines as well as cells with immunosuppressive phenotypes such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). The immune components and tumor immune responses in malignant and benign SGTs are still under investigation. Immune responses may directly play a limiting role in tumor growth and expansion, or may participate in formation of a rich milieu for tumor growth in cooperation with other cellular and regulatory molecules. Immune checkpoint molecules (e.g. PDLs, HLA-G and LAG3) are frequently expressed on tumor cells and/or tumor-infiltrating lymphocytes (TILs) in salivary gland microenvironment, and an increase in their expression is associated with T cell exhaustion, immune tolerance and tumor immune escape. Chemokines and chemokine receptors have influential roles on aggressive behaviors of SGTs, and thereby they could be candidate targets for cancer immunotherapy. To present a broad knowledge on salivary glands, this review first provides a brief description on immunological functions of normal salivary glands, and then describe the SGT's tumor microenvironment, by focusing on mesenchymal stem cells, immune cell subsets, immune checkpoint molecules, chemokines and chemokine receptors, and finally introduces immune checkpoint inhibitors as well as potential targets for cancer therapy.
Subject(s)
Immune Checkpoint Proteins , Salivary Gland Neoplasms , Humans , Salivary Gland Neoplasms/therapy , Salivary Gland Neoplasms/genetics , Salivary Gland Neoplasms/metabolism , Salivary Glands/metabolism , Salivary Glands/pathology , Chemokines , Receptors, Chemokine , Tumor Microenvironment , ImmunotherapyABSTRACT
There have been very rare reports on the migration of foreign bodies that are left or implanted in the body, and so far, they have only been reported in the gastrointestinal tract and intestines (a process similar to phagocytosis), later manifesting as an obstruction in the lumen. Meanwhile, no such cases have yet been reported in the cardiovascular system. The case reported here is a 14-month-old girl who had undergone pulmonary artery banding (PA band made of PTFE) around the pulmonary artery at the age of 8 months due to severe pulmonary hypertension and failure to thrive. She underwent reoperation six months later for a final treatment. It was discovered that the PA band was no longer around the pulmonary artery and had migrated completely into the pulmonary artery while remaining intact and circular and was drawn into the pulmonary artery in a process similar to phagocytosis. The PA band was removed completely. The uneven surface inside the main pulmonary artery was resected and the artery was repaired end-to-end. A total heart repair surgery was again performed on the patient. No problem was observed in the 2.5-year follow-up after the second surgery. Overall, the authors' case is the first instance of migration of a biologically-neutral foreign body into the cardiovascular system that had occurred six months after the PA-band implantation, and the first case of erosion of a foreign body into the lumen outside the gastrointestinal tract. Although the authors could not find the cause of the presented case, reports on future cases can help find the underlying reason.
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Determining clinically relevant physiological states from multivariate time-series data with missing values is essential for providing appropriate treatment for acute conditions such as Traumatic Brain Injury (TBI), respiratory failure, and heart failure. Utilizing non-temporal clustering or data imputation and aggregation techniques may lead to loss of valuable information and biased analyses. In our study, we apply the SLAC-Time algorithm, an innovative self-supervision-based approach that maintains data integrity by avoiding imputation or aggregation, offering a more useful representation of acute patient states. By using SLAC-Time to cluster data in a large research dataset, we identified three distinct TBI physiological states and their specific feature profiles. We employed various clustering evaluation metrics and incorporated input from a clinical domain expert to validate and interpret the identified physiological states. Further, we discovered how specific clinical events and interventions can influence patient states and state transitions.
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Brain Injuries, Traumatic , Humans , Brain Injuries, Traumatic/diagnosis , Algorithms , Cluster Analysis , Time Factors , BenchmarkingABSTRACT
In this paper, we examined informatics challenges and opportunities related to emergency department visit data during public health emergencies. We investigated the impact of COVID-19 pandemic on the volume and acuity of adult patients visiting the emergency department (ED) of a medical center in Arizona during the pandemic compared to the pre-pandemic period. We performed a negative binomial regression analysis to understand how different public health-related mandates and statewide business opening/closing orders in Arizona affected the daily emergency department visits. The results of this study show that the average daily ED visits decreased by 20% during the COVID-19 pandemic in comparison with the same period in 2019. In addition, the business closure order had the most impact on emergency department visits in comparison to other public health mandates.
Subject(s)
COVID-19 , Pandemics , Adult , COVID-19/epidemiology , Emergency Service, Hospital , Humans , Informatics , Public HealthABSTRACT
Lack of protein-coding capacity is a main characteristic of long noncoding RNAs (lncRNAs) which, as molecular biomarkers, have found a novel pharmacological application in cancer and are reported to be important regulators of gene expression. H19 is reportedly involved in cancer progression and tumorigenesis. One of the most common types of head and neck cancers is oral squamous cell carcinoma (OSCC). The main objective of the present study was to evaluate the correlation of OSCC susceptibility with H19 gene in an Iranian population. This research was performed on 400 subjects of both sexes referred to the Namazi Hospital affiliated with the Shiraz University of Medical Sciences (SUMS). Individuals aged 15-88 years were divided into two groups: pathologically diagnosed patients with new-onset OSCC and healthy controls. After written and informed consent was obtained from the individuals, genomic DNA was extracted. The tetra-primer ARMS-PCR technique was performed for DNA genotyping by the use of specific primer pairs. The susceptibility of OSCC and H19 gene polymorphism sites was further analyzed (rs217727 and rs2107425). The allele and genotype frequencies of H19 rs2107425 polymorphism were similar between OSCC cases and controls. The H19 rs217727T allele frequency was significantly higher in OSCC cases (P = 0.002), and the polymorphism of H19 rs217727 was associated with OSCC susceptibility in the codominant (OR = 6.04, 95%CI = 1.70 - 21.42, P = 0.001 for TT genotype), dominant (OR = 1.62, 95%CI = 1.08 - 2.43, P = 0.01), and recessive (OR = 5.32, 95%CI = 1.51 - 18.69, P = 0.003) models. This study showed that rs217727 and OSCC susceptibility were statistically correlated in the Iranian population.
Subject(s)
Genetic Predisposition to Disease/genetics , Mouth Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , RNA, Long Noncoding/genetics , Squamous Cell Carcinoma of Head and Neck/genetics , Adult , Aged , Case-Control Studies , Female , Genetic Predisposition to Disease/epidemiology , Genotype , Humans , Iran/epidemiology , Male , Middle Aged , Mouth Neoplasms/epidemiology , Squamous Cell Carcinoma of Head and Neck/epidemiologyABSTRACT
Background: The association between programmed cell death protein 1 (PD-1) variations and susceptibility to autoimmune diseases has been recurrently reported. However, there is no report about its relationship with oral lichen planus (OLP) as one of autoimmune diseases. Methods: We investigated the association between genetic predisposition to OLP and two single nucleotide polymorphisms in PD-1. Results: GG, GA, and AA genotypes at position +7146 were found in 59 (80.8 %), 10 (13.7 %), and 4 (5.5 %) patients, and in 132 (77 %), 34 (20 %), and 5 (3 %) healthy participants. CC, CT, and TT genotypes at position +7785 were found in 32 (43.8 %), 35 (47.9 %), and 6 (8.2 %) patients and in 99 (58 %), 66 (39 %), and 6 (3 %) controls. Analysis indicated that patients' genotypes were not statistically different from controls' genotypes at both positions +7146 (P = 0.35 and P = 0.98) and +7785 (P = 0.07 and P = 0.06). Conclusion: The findings indicated that PD-1 SNPs at +7146 [PD-1.3] G/A and +7785 [PD-1.5] C/T was not associated with susceptibility to OLP. However, further research with higher sample size and in different geographical regions is needed in order to achieve the generalizability of the findings.
Subject(s)
Biomarkers/analysis , Lichen Planus, Oral/genetics , Polymorphism, Single Nucleotide , Programmed Cell Death 1 Receptor/genetics , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Follow-Up Studies , Genotype , Humans , Lichen Planus, Oral/pathology , Male , Middle Aged , PrognosisABSTRACT
BACKGROUND: Critical aortic stenosis (AS) is an unusual cardiac pathology in pregnancy, but has significant impact on the fetal and maternal outcomes of pregnancy. Pregnant patients with aortic stenosis and heart failure represent a major challenge for the heart team and anesthesiologist who should balance the risks and benefits of different treatment strategies and their effects on the mother and fetus. CASE REPORT: We present a 26-year-old parturient who underwent cesarean section at 30 weeks of gestation under general anesthesia in the presence of cardiac surgical team followed by deferred aortic valve replacement after two weeks. CONCLUSION: This report describes the importance of multidisciplinary preoperative evaluation, and careful surgical and anesthetic planning to avoid the deterioration of perioperative cardiac condition in such patients.
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STATEMENT OF THE PROBLEM: One major goal of tissue engineering and regenerative medicine is to find an appropriate source of mesenchymal stem cells (MSCs) with higher differentiation ability. PURPOSE: In this experimental study, the osteogenic and chondrogenic differentiation ability of buccal fat pad derived MSCs (BFP-MSCs) with gingival derived cells (GDCs) were compared. MATERIALS AND METHOD: BFP-MSCs and GDCs were cultured enzymatically and expanded. The expanded cells were analyzed for membrane-associated markers, using flow cytometry. Then the ability of these cells to differentiate into osteocyte and chondrocyte was assessed morphologically and by mRNA expression of collagen I (COLL), BGLA and bone morphogenetic protein 2 (BMP2) using qRT-PCR. RESULTS: Flow cytometry analysis showed that both BFP-MSCs and GDCs expressed the characteristic stem cell markers such as CD73, CD44, and CD90, whereas they did not express hematopoietic markers. Mineralized calcium deposition was observed apparently in BFP-MSCs cultured in osteogenic medium but GDCs showed fewer mineralized nodules. The mRNA expression levels of BGLA and BMP2 showed 7×105 and 733-fold more mRNA expression in BFP-MSCs treated with differentiation media compared to the control group. In chondrogenic differentiation, BFP-MSCs transformed from a spindle to a cuboidal shape while GDCs showed only a slight transformation. In addition, mRNA expression of COLL showed 282-fold higher expression in BFP-MSCs in comparison to the control group. Such significant difference in mRNA expression of BGLA, BMP2, and COLL was not observed in GDCs compared to their corresponding controls. CONCLUSION: Based on the present results, BFP yields a greater proportion of stem cells compared to gingiva. Therefore, this tissue can be introduced as an easily available source for the treatment of periodontal defects and other maxillofacial injuries.
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Pericardial cysts are rare lesions. These benign anomalies are located in the middle mediastinum. In this article, we present a 24-year-old man who was referred to the emergency department with dyspnea and persistent cough. In physical exam, no abnormality was found. His past medical history was normal. His trans-thoracic echocardiogram showed an echo-lucent space next to the right atrium at the right cardiophrenic angle. No pericardial effusion was found. The patient underwent surgery. After midsternotomy, a huge cyst measuring approximately 13 × 8 × 5 cm in diameters was found on the right side and outside the pericardium that was totally excised. After 5 days, the patient was discharged and pathologic report confirmed preoperative diagnosis of pericardial cyst. Giant pericardial cysts are not common and in this report, we will review published case reports.
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Guillain-Barre syndrome is a neurologic disorder that may appear after infection or major surgery. Guillain-Barré syndrome following cardiac surgery is rare and only based on case reports, and we review all of the published cases. A 52-year-old man after 5 months suffering from chest pain was referred to our hospital and underwent coronary artery bypass graft for 3 vessel disease. The patient was discharged without complication on the 5th postoperative day. He presented Guillain-Barré syndrome after 12 months. He has not completely recovered weakness of upper extremities grade 4/5 with atrophy of both upper extremities remains after 18 months. This disorder is similar to classic GBS. It is important to be alert to de novo autoimmune neurological disorders after cardiac surgery. These disorders are similar to classic autoimmune disease and treated with standard therapies.
Subject(s)
Coronary Artery Bypass/adverse effects , Guillain-Barre Syndrome/etiology , Humans , Male , Middle AgedABSTRACT
At the final stages of a coronary artery bypass graft operation on a 64-year-old man, an experienced physician attempted to insert an intra-aortic balloon pump into the femoral artery via the Seldinger technique. However, while the balloon pump was being passed over the guide wire, the latter was completely lost. The guide wire should be held at the tip at all times to prevent passage into the vessel. Strict adherence to this rule will prevent guide-wire loss, which is, albeit rare and completely avoidable, a potentially life-threatening complication of central vein or artery catheterization, with reported fatality rates of up to 20% when the whole wire is lost. The literature contains several reports on guide-wire loss during central venous, arterial, and hemodialysis catheterization, but we report for the first time the loss of a guide wire as a rare complication of intra-aortic balloon pump insertion.
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UNLABELLED: Although cardiac tumors are not common they may vary in terms of race and surgical approach in different countries. METHOD: Patients data of 20 years was collected and evaluated in the "Shahid Modarres Hospital"--a tertiary university hospital--Tehran, Iran. RESULTS: 42 patients with cardiac myxoma (all cases in 20 years) were included in study, 17 males and 25 females, age difference: 13 to 76 years (mean 50.6). Most of patients were in functional classes I, II. 35 patients complained of dyspnea and 3 patients had embolic events. 97.6% of tumors were primary (41 patients) and one tumor was recurrent (2.4%), 85.7% of tumors (36 cases) were located in LA, and 88.1% of tumors (37 cases) were pediculated. 40 patients (95%) had one tumor. In 22 patients (52.3%) after tumor resection septal defects were repaired primarily while in 18 patients (42.8%) the defects were repaired with pericardial patch and In one patient, tumor resected without any septal defect. Mean tumor size was about 5.22 cm (range of 2.2 to 8.2 cm). Postoperatively, 33 patients discharged from hospital without any complication. DISCUSSION: The research reveals that patients' age and gender were similar to that of other studies in other countries while tumor's incidence seems to be higher. 3 patients were diagnosed after remote embolic event and one patient was diagnosed after MI reflecting relatively high tumor complications and late diagnosis. CONCLUSION: In our study mean time from diagnosis to operation was too long. The patients had more preoperative embolic events and complication. However, size of myxoma and location of that was as same as its rate in the other literature. As recommendation we suggested that in all patients with vague chest pain or remote embolic events cardiac myxomas should be ruled out.