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As cells migrate through biological tissues, they must frequently squeeze through micron-sized constrictions in the form of interstitial pores between extracellular matrix fibers and/or other cells. Although it is now well recognized that such confined migration is limited by the nucleus, which is the largest and stiffest organelle, it remains incompletely understood how cells apply sufficient force to move their nucleus through small constrictions. Here, we report a mechanism by which contraction of the cell rear cortex pushes the nucleus forward to mediate nuclear transit through constrictions. Laser ablation of the rear cortex reveals that pushing forces behind the nucleus are the result of increased intracellular pressure in the rear compartment of the cell. The pushing forces behind the nucleus depend on accumulation of actomyosin in the rear cortex and require Rho kinase (ROCK) activity. Collectively, our results suggest a mechanism by which cells generate elevated intracellular pressure in the posterior compartment to facilitate nuclear transit through three-dimensional (3D) constrictions. This mechanism might supplement or even substitute for other mechanisms supporting nuclear transit, ensuring robust cell migrations in confined 3D environments.
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Movimiento Celular , Núcleo Celular , Núcleo Celular/metabolismo , Movimiento Celular/fisiología , Humanos , Actomiosina/metabolismo , Quinasas Asociadas a rho/metabolismo , Animales , Presión , RatonesRESUMEN
Cell traction force plays a critical role in directing cellular functions, such as proliferation, migration, and differentiation. Current understanding of cell traction force is largely derived from 2D measurements where cells are plated on 2D substrates. However, 2D measurements do not recapitulate a vital aspect of living systems; that is, cells actively remodel their surrounding extracellular matrix (ECM), and the remodeled ECM, in return, can have a profound impact on cell phenotype and traction force generation. This reciprocal adaptivity of living systems is encoded in the material properties of biological gels. In this review, we summarize recent progress in measuring cell traction force for cells embedded within 3D biological gels, with an emphasis on cell-ECM cross talk. We also provide perspectives on tools and techniques that could be adapted to measure cell traction force in complex biochemical and biophysical environments.
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Matriz Extracelular , Esferoides Celulares , Humanos , Matriz Extracelular/metabolismo , Esferoides Celulares/citología , Animales , Movimiento Celular , Geles/química , Adhesión Celular , Microscopía de Fuerza Atómica/métodos , Análisis de la Célula Individual/métodos , Hidrogeles/químicaRESUMEN
One of the hallmarks of cancer cells is their exceptional ability to migrate within the extracellular matrix (ECM) for gaining access to the circulatory system, a critical step of cancer metastasis. RhoA, a small GTPase, is known to be a key molecular switch that toggles between actomyosin contractility and lamellipodial protrusion during cell migration. Current understanding of RhoA activity in cell migration has been largely derived from studies of cells plated on a two-dimensional (2D) substrate using a FRET biosensor. There has been increasing evidence that cells behave differently in a more physiologically relevant three-dimensional (3D) environment. However, studies of RhoA activities in 3D have been hindered by low signal-to-noise ratio in fluorescence imaging. In this paper, we present a a machine learning-assisted FRET technique to follow the spatiotemporal dynamics of RhoA activities of single breast tumor cells (MDA-MB-231) migrating in a 3D as well as a 2D environment. We found that RhoA activity is more polarized along the long axis of the cell for single cells migrating on 2D fibronectin-coated glass versus those embedded in 3D collagen matrices. In particular, RhoA activities of cells in 2D exhibit a distinct front-to-back and back-to-front movement during migration in contrast to those in 3D. Finally, regardless of dimensionality, RhoA polarization is found to be moderately correlated with cell shape.
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Neoplasias de la Mama/metabolismo , Transferencia Resonante de Energía de Fluorescencia , Aprendizaje Automático , Proteína de Unión al GTP rhoA/metabolismo , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Polaridad Celular , Forma de la Célula , Colágeno/metabolismo , Femenino , Humanos , Ratas , Factores de TiempoRESUMEN
ABSTRACT: This case reports on the use of wavefront-guided (wfg) optics on custom ocular impression-based scleral lenses (IBSLs) for visual improvement in a patient with keratoconus (KC). A 28-year-old man with KC, who had previously failed a traditional, diagnostically fit scleral lens (tSL), was fit with IBSLs with traditional optics. Using a system that included a dot matrix on the IBSL and a wavefront aberrometer with pupil and dot registration software, a wfgIBSL was created. When compared with the IBSL, the wfgIBSL reduced the total higher-order root mean square (HORMS) 67% and 64% in the right and left eye, respectively, resulting in a 2-line improvement in best-contact lens visual acuity (BCLVA) for both eyes. This case demonstrates the successful creation and application of a wfgIBSL resulting in a stable lens, a reduction in HORMS, and an improvement in BCLVA, after failure with a diagnostically fit tSL.
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Lentes de Contacto , Queratocono , Cristalino , Masculino , Humanos , Adulto , Queratocono/complicaciones , Queratocono/terapia , Esclerótica , Agudeza VisualRESUMEN
PURPOSE: Near infrared spectroscopy (NIRS) measures tissue oximetry and perfusion of free tissue transfer with the advantage of remote wireless monitoring for free tissue transfer. It has been widely used in breast and extremity reconstruction but has had limited adoption in the head and neck. MATERIALS AND METHODS: A retrospective review of head and neck microvascular reconstruction by three different surgical services over 15 months at one tertiary care hospital was performed. Demographics, flap type, monitoring technique, complications, and flap outcomes were recorded. Monitoring techniques were (1) implantable/handheld Doppler or (2) NIRS. Flap monitoring outcomes were evaluated using multivariate analysis. RESULTS: 119 flaps were performed by four surgeons with a success rate of 92% (109/119). Flaps were monitored with Doppler (40%) or NIRS (60%). There was no difference in flap success based on monitoring technique. An ROC analysis identified that the optimal cutoff in immediate StO2 for classifying flap success at discharge was 68%. CONCLUSIONS: NIRS was successfully implemented in a high-volume head and neck reconstructive practice. NIRS remote monitoring allowed for flap surveillance without requiring in-hospital presence and was able to identify both arterial and venous compromise.
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Neoplasias de Cabeza y Cuello/cirugía , Microvasos/cirugía , Monitoreo Fisiológico/métodos , Oximetría/métodos , Perfusión/métodos , Procedimientos de Cirugía Plástica/métodos , Tecnología de Sensores Remotos/métodos , Espectroscopía Infrarroja Corta , Colgajos Quirúrgicos/fisiología , Colgajos Quirúrgicos/trasplante , Procedimientos Quirúrgicos Vasculares/métodos , Anciano , Femenino , Neoplasias de Cabeza y Cuello/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Moving from group level to individual level functional parcellation maps is a critical step for developing a rich understanding of the links between individual variation in functional network architecture and cognitive and clinical phenotypes. Still, the identification of functional units in the brain based on intrinsic functional connectivity and its dynamic variations between and within subjects remains challenging. Recently, the bootstrap analysis of stable clusters (BASC) framework was developed to quantify the stability of functional brain networks both across and within subjects. This multi-level approach utilizes bootstrap resampling for both individual and group-level clustering to delineate functional units based on their consistency across and within subjects, while providing a measure of their stability. Here, we optimized the BASC framework for functional parcellation of the basal ganglia by investigating a variety of clustering algorithms and similarity measures. Reproducibility and test-retest reliability were computed to validate this analytic framework as a tool to describe inter-individual differences in the stability of functional networks. The functional parcellation revealed by stable clusters replicated previous divisions found in the basal ganglia based on intrinsic functional connectivity. While we found moderate to high reproducibility, test-retest reliability was high at the boundaries of the functional units as well as within their cores. This is interesting because the boundaries between functional networks have been shown to explain most individual phenotypic variability. The current study provides evidence for the consistency of the parcellation of the basal ganglia, and provides the first group level parcellation built from individual-level cluster solutions. These novel results demonstrate the utility of BASC for quantifying inter-individual differences in the functional organization of brain regions, and encourage usage in future studies.
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Ganglios Basales/diagnóstico por imagen , Ganglios Basales/fisiología , Mapeo Encefálico/métodos , Individualidad , Imagen por Resonancia Magnética/métodos , Adulto , Mapeo Encefálico/normas , Femenino , Humanos , Imagen por Resonancia Magnética/normas , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or instead utilize existing extracellular matrix microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3-dimensional migration, few recapitulate these natural migration paths. Here, we develop a biopolymer-based bicontinuous hydrogel system that comprises a covalent hydrogel of enzymatically crosslinked gelatin and a physical hydrogel of guest and host moieties bonded to hyaluronic acid. Bicontinuous hydrogels form through controlled solution immiscibility, and their continuous subdomains and high micro-interfacial surface area enable rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior is mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which is shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a design that leverages important local interfaces to guide rapid cell migration.
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Matriz Extracelular , Hidrogeles , Hidrogeles/química , Movimiento Celular , Matriz Extracelular/metabolismo , Esferoides Celulares , Biopolímeros/metabolismoRESUMEN
Background: Vitamin D deficiency (VDD) is associated with coronary heart disease (CHD) and poor outcomes, but supplementation does not improve prognosis. VDD has been implicated in and may promote greater risk through inflammation and impaired progenitor cell function. Objectives: The authors examined VDD, high-sensitivity C-reactive protein (hsCRP), circulating progenitor cell (CPC) counts, and outcomes in patients with CHD. They hypothesized that the higher risk with VDD is mediated by inflammation and impaired regenerative capacity. Methods: A total of 5,452 individuals with CHD in the Emory Cardiovascular Biobank had measurement of 25-hydroxyvitamin D, subsets of whom had hsCRP measurements and CPCs estimated as CD34-expressing mononuclear cell counts. Findings were validated in an independent cohort. 25-hydroxyvitamin D <20 ng/mL was considered VDD. Cox and Fine-Gray models determined associations between marker levels and: 1) all-cause mortality; 2) cardiovascular mortality; and 3) major adverse cardiovascular events, a composite of adverse CHD outcomes. Results: VDD (43.6% of individuals) was associated with higher adjusted cardiovascular mortality (HR: 1.57, 95% CI: 1.09-2.28). There were significant interactions between VDD and hsCRP and CPC counts in predicting cardiovascular mortality. Individuals with both VDD and elevated hsCRP had the greatest risk (HR: 2.82, 95% CI: 2.16-3.67). Only individuals with both VDD and low CPC counts were at high risk (HR: 2.25, 95% CI: 1.46-3.46). These findings were reproduced in the validation cohort. Conclusions: VDD predicts adverse outcomes in CHD. Those with VDD, inflammation and/or diminished regenerative capacity are at a significantly greater risk of cardiovascular mortality. Whether targeted supplementation in these high-risk groups improves risk warrants further study.
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Functional connectomics is one of the most rapidly expanding areas of neuroimaging research. Yet, concerns remain regarding the use of resting-state fMRI (R-fMRI) to characterize inter-individual variation in the functional connectome. In particular, recent findings that "micro" head movements can introduce artifactual inter-individual and group-related differences in R-fMRI metrics have raised concerns. Here, we first build on prior demonstrations of regional variation in the magnitude of framewise displacements associated with a given head movement, by providing a comprehensive voxel-based examination of the impact of motion on the BOLD signal (i.e., motion-BOLD relationships). Positive motion-BOLD relationships were detected in primary and supplementary motor areas, particularly in low motion datasets. Negative motion-BOLD relationships were most prominent in prefrontal regions, and expanded throughout the brain in high motion datasets (e.g., children). Scrubbing of volumes with FD>0.2 effectively removed negative but not positive correlations; these findings suggest that positive relationships may reflect neural origins of motion while negative relationships are likely to originate from motion artifact. We also examined the ability of motion correction strategies to eliminate artifactual differences related to motion among individuals and between groups for a broad array of voxel-wise R-fMRI metrics. Residual relationships between motion and the examined R-fMRI metrics remained for all correction approaches, underscoring the need to covary motion effects at the group-level. Notably, global signal regression reduced relationships between motion and inter-individual differences in correlation-based R-fMRI metrics; Z-standardization (mean-centering and variance normalization) of subject-level maps for R-fMRI metrics prior to group-level analyses demonstrated similar advantages. Finally, our test-retest (TRT) analyses revealed significant motion effects on TRT reliability for R-fMRI metrics. Generally, motion compromised reliability of R-fMRI metrics, with the exception of those based on frequency characteristics - particularly, amplitude of low frequency fluctuations (ALFF). The implications of our findings for decision-making regarding the assessment and correction of motion are discussed, as are insights into potential differences among volume-based metrics of motion.
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Artefactos , Mapeo Encefálico/métodos , Encéfalo/fisiología , Conectoma/métodos , Vías Nerviosas/fisiología , Movimientos de la Cabeza , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Movimiento (Física) , Descanso/fisiologíaRESUMEN
Dyslipidemia is a treatable risk factor for atherosclerotic cardiovascular disease that can be addressed through lifestyle changes and/or lipid-lowering therapies. Adherence to statins can be a clinical challenge in some patients due to statin-associated muscle symptoms and other side effects. There is a growing interest in integrative cardiology and nutraceuticals in the management of dyslipidemia, as some patients desire or are actively seeking a more natural approach. These agents have been used in patients with and without established atherosclerotic cardiovascular disease. We provide an updated review of the evidence on many new and emerging nutraceuticals. We describe the mechanism of action, lipid-lowering effects, and side effects of many nutraceuticals, including red yeast rice, bergamot and others.
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Mechanical properties of the extracellular matrices (ECMs) critically regulate a number of important cell function including growth, differentiation and migration. Type I collagen and glycosaminoglycans (GAGs) are two primary components of ECMs that contribute to tissue mechanics with the collagen fiber network sustaining tension and GAGs withstanding compression. Collagen stiffness as well as its architecture are known to be important role players in cell-ECM mechanical interactions, however, much less is known about how GAGs within ECMs regulate cell force generation and invasion. Inspired by a recent theoretical work from the Shenoy lab that GAGs play important roles in cell - ECM interactions, we hereby present experimental studies on the role of hyaluronic acid (HA, an unsulfated GAG) in single tumor cell traction force generation within HA collagen cogels using a recently developed 3D cell traction force microscopy. Our work revealed that CD44, a cell surface adhesion receptor to HA, was engaged in cell traction force generation in conjunction with ß1-integrin. Furthermore, we found that HA significantly modified the architecture and mechanics of the collagen fiber network, decreased tumor cells' propensity to remodel the collagen network, decreased traction force generation and transmission distance, and attenuated tumor invasion in agreement with theoretical predictions. Our findings highlighted the significance of CD44 and HA engagement in cell-ECM mechanical interactions, providing new insights on the mechanical model of cellular force transmission.
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Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or may instead utilize existing ECM microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3D migration, few have recapitulated these natural migration paths. Here, we developed a biopolymer-based (i.e., gelatin and hyaluronic acid) bicontinuous hydrogel system formed through controlled solution immiscibility whose continuous subdomains and high micro-interfacial surface area enabled rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior was mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which was shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a new design that leverages important local interfaces to guide rapid cell migration.
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Importance: The clinical significance of hemodynamic reactivity to mental stress in the population with coronary artery disease (CAD) is unclear. Objective: To investigate the association between hemodynamic reactivity to mental stress and the risk of adverse cardiovascular events in patients with stable CAD. Design, Setting, and Participants: This cohort study included individuals with stable CAD from 2 prospective studies from a university-based hospital network: the Mental Stress Ischemia Prognosis Study (MIPS) and the Myocardial Infarction and Mental Stress Study 2 (MIMS2). Participants were enrolled between June 2011 and March 2016 and followed up for a median of 6.0 (IQR, 5.6-6.0) years in MIPS and 4.6 (IQR, 3.8-5.3) years in MIMS2. Data were analyzed from December 1, 2022, to February 15, 2023. Exposures: The rate-pressure product (RPP) was calculated as the mean systolic blood pressure times the mean heart rate at rest. Rate-pressure product reactivity was calculated as the maximum RPP during a standardized mental stress test minus the RPP at rest. Main Outcomes and Measures: The primary outcome was a composite of cardiovascular death or nonfatal myocardial infarction. The secondary end point additionally included hospitalizations for heart failure. Results: From the total of 938 individuals from the pooled cohort (mean [SD] age, 60.2 [10.1] years; 611 [65.1%] men), 631 participated in MIPS and 307 in MIMS2. A total of 373 individuals (39.8%) were Black, 519 (55.3%) were White, and 46 (4.9%) were of unknown race or ethnicity. The RPP increased by a mean (SD) of 77.1% (23.1%) during mental stress (mean [SD] absolute change, 5651 [2878]). For every SD decrease in RPP reactivity with mental stress, the adjusted hazard ratios for the primary and secondary end points were 1.30 (95% CI, 1.04-1.72) and 1.30 (95% CI, 1.06-1.56), respectively, in MIPS and 1.41 (95% CI, 1.06-1.97) and 1.21 (95% CI, 1.02-1.60), respectively, in MIMS2. In the pooled sample, when RPP reactivity to mental stress was added to a model including traditional clinical risk characteristics, model discrimination for adverse events improved (increase in C statistic of 5% for the primary end point; P = .009). Conclusions and Relevance: In this cohort study of individuals with stable CAD, a blunted cardiovascular reactivity to mental stress was associated with adverse outcomes. Future studies are needed to assess the clinical utility of mental stress reactivity testing in this population.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios de Cohortes , Estudios Prospectivos , Infarto del Miocardio/epidemiología , Infarto del Miocardio/complicaciones , HemodinámicaRESUMEN
Although artificial neural networks (ANNs) were inspired by the brain, ANNs exhibit a brittleness not generally observed in human perception. One shortcoming of ANNs is their susceptibility to adversarial perturbations-subtle modulations of natural images that result in changes to classification decisions, such as confidently mislabelling an image of an elephant, initially classified correctly, as a clock. In contrast, a human observer might well dismiss the perturbations as an innocuous imaging artifact. This phenomenon may point to a fundamental difference between human and machine perception, but it drives one to ask whether human sensitivity to adversarial perturbations might be revealed with appropriate behavioral measures. Here, we find that adversarial perturbations that fool ANNs similarly bias human choice. We further show that the effect is more likely driven by higher-order statistics of natural images to which both humans and ANNs are sensitive, rather than by the detailed architecture of the ANN.
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Encéfalo , Redes Neurales de la Computación , Humanos , Encéfalo/diagnóstico por imagen , PercepciónRESUMEN
Objective: Coronary heart disease is a leading cause of death and disability. Although psychological stress has been identified as an important potential contributor, mechanisms by which stress increases risk of heart disease and mortality are not fully understood. The purpose of this study was to assess mechanisms by which stress acts through the brain and heart to confer increased CHD risk. Methods: Coronary Heart Disease patients (N=10) underwent cardiac imaging with [Tc-99m] sestamibi single photon emission tomography at rest and during a public speaking mental stress task. Patients returned for a second day and underwent positron emission tomography imaging of the brain, heart, bone marrow, aorta (indicating inflammation) and subcutaneous adipose tissue, after injection of [18F]2-fluoro-2-deoxyglucose for assessment of glucose uptake followed mental stress. Patients with (N=4) and without (N=6) mental stress-induced myocardial ischemia were compared for glucose uptake in brain, heart, adipose tissue and aorta with mental stress. Results: Patients with mental stress-induced ischemia showed a pattern of increased uptake in the heart, medial prefrontal cortex, and adipose tissue with stress. In the heart disease group as a whole, activity increase with stress in the medial prefrontal brain and amygdala correlated with stress-induced increases in spleen (r=0.69, p=0.038; and r=0.69, p=0.04 respectfully). Stress-induced frontal lobe increased uptake correlated with stress-induced aorta uptake (r=0.71, p=0.016). Activity in insula and medial prefrontal cortex was correlated with post-stress activity in bone marrow and adipose tissue. Activity in other brain areas not implicated in stress did not show similar correlations. Increases in medial prefrontal activity with stress correlated with increased cardiac glucose uptake with stress, suggestive of myocardial ischemia (r=0.85, p=0.004). Conclusions: These findings suggest a link between brain response to stress in key areas mediating emotion and peripheral organs involved in inflammation and hematopoietic activity, as well as myocardial ischemia, in Coronary Heart Disease patients.
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Acute suppurative thyroiditis (AST) is a rare infection of the thyroid gland, and most patients are euthyroid upon presentation. We present an interesting case of a 42-year-old man with a history of intravenous drug use (IVDU) and poorly controlled type 2 diabetes mellitus who was admitted for sepsis and thyrotoxicosis from infective endocarditis (IE), AST, prostate abscess, and pyelonephritis. He suffered from a cerebral vascular accident (CVA) from septic embolic showering. Thyroid-stimulating hormone (TSH) was <0.10 mIU/L, and free thyroxine (T4) levels were>90 pmol/L. Methicillin-resistant Staphylococcus aureus (MRSA) was cultured in the patient's blood and urine. He was treated with prompt intravenous (IV) antimicrobials and source control from a transurethral resection of the prostate. This case demonstrates that AST can be a potential complication of IE and IVDU.
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BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is a paraneoplastic phenomenon with sterile vegetations. It is associated with adenocarcinoma and can shower emboli, which can be the presenting symptom. CASE PRESENTATION: A 44-year-old woman with adenocarcinoma of the lung presented with chest pain, left hand weakness, and ataxia due to repeated embolic showering from NBTE to the central nervous system (CNS) and spleen. CONCLUSION: NBTE is a rare condition that should be on the differential diagnosis in patients with culture-negative endocarditis and a history of adenocarcinoma. LEARNING POINTS: Differentiating non-bacterial thrombotic endocarditis (NBTE) from infective endocarditis can be a diagnostic challenge due to slow growing organisms; laboratory findings that suggest NBTE include the lack of leucocytosis, normal C-reactive protein, negative blood culture sets, and positive antiphospholipid antibodies.Serial transesophageal echocardiogram (TEE) should be performed if suspicion of valvular vegetations is high despite the initial TEE showing no vegetations.The mainstay treatment of NBTE is anticoagulation and addressing the underlying condition.
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This report describes a case involving a balloon kyphoplasty bone tamp becoming lodged inside the vertebral body and unable to be withdrawn, the first report of its kind in the literature. A board certified interventional pain management physician was performing a balloon kyphoplasty for an L3 osteoporotic vertebral compression fracture using a bipedicular approach with two bone tamps. Cannulation and cavity formation were completed without complication; however, upon removal of the balloons it was noted that one had become lodged in the vertebral body. Several attempts were made to remove the balloon. Neurosurgery and the balloon manufacturer were consulted intraoperative, and it was decided to leave the balloon fragments in situ and complete the interventional fixation of the vertebral body with bone cement. The patient followed up in the clinic several months later without neurologic complications. Postoperative radiography confirmed the presence of a retained foreign body consistent with balloon fragments. Balloon kyphoplasty and its various procedural complications will be discussed, as well as the intraoperative decision making faced when encountering a complication.
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INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in the United States, and efforts have been made to develop termination of resuscitation protocols utilizing clinical criteria predictive of successful resuscitation and survival to discharge. A termination of resuscitation protocol utilizing longer resuscitation time and end-tidal carbon dioxide (EtCO2) monitoring criteria for termination was implemented for Emergency Medical Service (EMS) providers in an urban prehospital system in 2017. This study examines the effect the modified termination of resuscitation protocol had on rates of patient transport to a hospital, return of spontaneous circulation (ROSC), and survival to discharge. METHODS: A retrospective analysis was performed utilizing data from the Cardiac Arrest Registry to Enhance Survival (CARES) database. A total of 1,005 prehospital cardiac arrest patients 18 years and older from 2016 through 2017 were included in the analysis. Patients with traumatic cardiac arrest or had valid do-not-resuscitate orders were excluded. Unadjusted analysis using chi-square statistics was performed, including an analysis stratified by Utstein style reporting. Adjusted analysis was also performed using logistic regression with multiple imputation for missing values. RESULTS: Unadjusted analysis showed a significant decrease in ROSC on emergency department (ED) arrival (30% versus 13%; P <.001) following the change in protocol. There was no significant difference in patient transport rate (62%) and a statistically non-significant decrease in overall survival (15% versus 11%). When stratified by Utstein style analysis, statistically significant decreases in ED arrival with ROSC were seen for unwitnessed asystolic, as well as bystander witnessed asystolic, pulseless electrical activity (PEA), and shockable OHCA. Adjusted analysis showed a decreased likelihood of ROSC with the protocol change (0.337; 95% CI, 0.235-0.482). CONCLUSION: The modification of termination of resuscitation protocol was not associated with a statistically significant change in transport rate or survival. A significant decrease in rate of arrivals to the ED with ROSC was seen, particularly for bystander witnessed OHCA.
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Dióxido de Carbono/análisis , Reanimación Cardiopulmonar , Paro Cardíaco Extrahospitalario/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pruebas Respiratorias , Bases de Datos Factuales , Servicios Médicos de Urgencia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/fisiopatología , Estudios Retrospectivos , Estados Unidos , Población Urbana , Adulto JovenRESUMEN
Borrelia burgdorferi (B. burgdorferi) is a spirochete bacterium that is transmitted via the Ixodes tick. Infection results in Lyme disease with possible cardiac manifestations, which is also known as Lyme carditis. Patients can present with bradycardia due to rapidly fluctuating atrioventricular block (AVB), which is the hallmark of Lyme carditis. However, we present a rare case of sick sinus syndrome (SSS) without AVB in a 47-year-old man with Lyme disease. He initially presented with a headache and subsequently developed new onset bradycardia and a right cranial nerve (CN) VI palsy with diplopia. B. burgdorferi enzyme-linked immunosorbent assay (ELISA) screen and IgM western blot were positive. He was admitted to the intensive care unit. Electrocardiography (EKG) indicated a heart rate in the high 30â¯s beats per minute (BPM) with several pauses, but no AVB was present. The patient responded well to therapy, and was discharged with an outpatient regimen of doxycycline. Lyme carditis should be considered in patients who develop new onset bradycardia and live in endemic areas.