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Transcatheter aortic valve replacement (TAVR) continues to grow in the United States. There are limited data on recipients of solid organ transplant (SOT) and patients with liver cirrhosis who undergo aortic valve replacement (AVR). Our study aims to evaluate outcomes in these populations. Using the national readmission database (2016 to 2020), we identified recipients of SOT and patients with liver cirrhosis without previous liver transplants who were admitted for severe aortic stenosis and underwent either TAVR or surgical AVR (SAVR). We used multivariable regression for adjusted analysis and the propensity score matching model, implementing complete Mahalanobis distance matching within the Propensity Score Caliper (0.2) to match TAVR and SAVR cohorts for outcomes. Of 3,394 hospitalizations for AVR in recipients of SOT, 2,181 underwent TAVR, and 1,213 underwent SAVR. On propensity-matched analysis, SAVR was associated with more adverse events than was TAVR, including in-hospital mortality (5.2% vs 1.1%, adjusted odds ratio [aOR] 4.49, p <0.001), acute kidney injury (43.7% vs 10.2%, p <0.001), cardiogenic shock (9.0% vs 1.6%, p <0.001), sudden cardiac arrest (15.9 vs 6.0%, p <0.001), major adverse cardiac and cerebrovascular events (28% vs 10.4%, p <0.001), and net adverse events (72.8 vs 37.6%, p <0.001). A greater median length of stay (10 vs 2 days, p <0.001) and adjusted cost ($80,842 vs $57,014, p <0.001) were also observed. The readmission rates were the same for both cohorts after a 6-month follow-up. Similarly, in 14,763 hospitalizations for AVR in liver cirrhosis, 7,109 patients underwent TAVR, and 7,654 underwent SAVR. In propensity-matched cohorts (nâ¯=â¯2,341), SAVR was found to be associated with greater adverse events, including in-hospital mortality (19.8% vs 10%, aOR 5.52), stroke (6.7% vs 2%), acute kidney injury (67.7% vs 30.3%), cardiogenic shock (41.9% vs 19.9%), sudden cardiac arrest (31.8% vs 13.2%, aOR 2.89), major adverse cardiac and cerebrovascular events (66.2% vs 35.7%), and net adverse events (86% vs 59.5%) (p <0.001). A greater median length of stay (16 vs 3 days) and cost ($500,218 vs $263,383) were also observed (p <0.001). However, the rate of readmissions at 30-day (9% vs 11.1%) and 180-day intervals (33.4% vs 39.8%) was lower for the SAVR cohort (p <0.05). In recipients of SOT and patients with liver cirrhosis, SAVR is associated with greater short-term mortality, adverse events, and healthcare burden than is TAVR. TAVR is a relatively safer alternative to SAVR in these patient populations, although further studies are warranted to compare the long-term outcomes.
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Background: Methamphetamine is an emerging drug threat. The disparity in cardiomyopathy-associated hospital admissions among methamphetamine users (CAHMA) over the decade remains unknown. Objectives: The purpose of this study was to determine the trends and prevalence of CAHMA by age, sex, race, and geographical region. Methods: We used data from 2008 to 2020 from the National Inpatient Sample database. We identified 12,845,919 cardiomyopathy-associated hospital admissions; among them, 222,727 were diagnosed as methamphetamine users. A generalized linear model with binomial link function was used to compute the prevalence ratio and 95% CI. Those who used other substances along with methamphetamine were excluded from the analysis. Results: CAHMA increased by 231% (P trend <0.001) from 2008 to 2020. CAHMA increased 345% for men (P trend <0.001) and 122% for women (P trend <0.001), 271% for non-Hispanic White (P trend <0.001), 254% for non-Hispanic Black (p trend <0.001), 565% for Hispanic (P trend <0.001), and 645% for non-Hispanic Asian (P trend <0.001) population. CAHMA also increased significantly in the West region (530%) (P trend <0.001) and South region (200%) (P trend <0.001) of the United States. Men, Hispanic population, age groups 26 to 40 and 41 to 64 years, and Western regions showed a significantly higher uptrend than their counterparts (P trend <0.001). Conclusions: CAHMA have increased significantly in the United States. Men, Hispanics, non-Hispanic Asian, age groups 41 to 64. and western regions showed a higher proportional increase highlighting gender-based, racial/ethnic, and regional disparities over the study period.
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Purpose: To train and validate a convolutional neural network to segment nonperfusion areas (NPAs) in multiple retinal vascular plexuses on widefield optical coherence tomography angiography (OCTA). Methods: This cross-sectional study included 202 participants with a full range of diabetic retinopathy (DR) severities (diabetes mellitus without retinopathy, mild to moderate non-proliferative DR, severe non-proliferative DR, and proliferative DR) and 39 healthy participants. Consecutive 6 × 6-mm OCTA scans at the central macula, optic disc, and temporal region in one eye from 202 participants in a clinical DR study were acquired with a 70-kHz OCT commercial system (RTVue-XR). Widefield OCTA en face images were generated by montaging the scans from these three regions. A projection-resolved OCTA algorithm was applied to remove projection artifacts at the voxel scale. A deep convolutional neural network with a parallel U-Net module was designed to detect NPAs and distinguish signal reduction artifacts from flow deficits in the superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Expert graders manually labeled NPAs and signal reduction artifacts for the ground truth. Sixfold cross-validation was used to evaluate the proposed algorithm on the entire dataset. Results: The proposed algorithm showed high agreement with the manually delineated ground truth for NPA detection in three retinal vascular plexuses on widefield OCTA (mean ± SD F-score: SVC, 0.84 ± 0.05; ICP, 0.87 ± 0.04; DCP, 0.83 ± 0.07). The extrafoveal avascular area in the DCP showed the best sensitivity for differentiating eyes with diabetes but no retinopathy (77%) from healthy controls and for differentiating DR by severity: DR versus no DR, 77%; referable DR (rDR) versus non-referable DR (nrDR), 79%; vision-threatening DR (vtDR) versus non-vision-threatening DR (nvtDR), 60%. The DCP also showed the best area under the receiver operating characteristic curve for distinguishing diabetes from healthy controls (96%), DR versus no DR (95%), and rDR versus nrDR (96%). The three-plexus-combined OCTA achieved the best result in differentiating vtDR and nvtDR (81.0%). Conclusions: A deep learning network can accurately segment NPAs in individual retinal vascular plexuses and improve DR diagnostic accuracy. Translational Relevance: Using a deep learning method to segment nonperfusion areas in widefield OCTA can potentially improve the diagnostic accuracy of diabetic retinopathy by OCT/OCTA systems.
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Retinopatia Diabética , Redes Neurais de Computação , Vasos Retinianos , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos , Retinopatia Diabética/diagnóstico por imagem , Retinopatia Diabética/diagnóstico , Estudos Transversais , Vasos Retinianos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Feminino , Angiofluoresceinografia/métodos , Idoso , Algoritmos , Adulto , Aprendizado ProfundoRESUMO
Purpose: To report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector. Design: Single-center, retrospective chart review. Methods: In this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated. Results: Three out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector. Conclusions: We observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes. Translational Relevance: Caution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.
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Terapia Genética , Vetores Genéticos , Tomografia de Coerência Óptica , Acuidade Visual , cis-trans-Isomerases , Humanos , Estudos Retrospectivos , Vetores Genéticos/genética , Terapia Genética/métodos , Masculino , Feminino , Criança , cis-trans-Isomerases/genética , Dependovirus/genética , Atrofia , Campos VisuaisRESUMO
There are several binding groups used within molecular electronics for anchoring molecules to metal electrodes (e.g., R-SMe, R-NH2, R-CS2 -, R-S-). However, some anchoring groups that bind strongly to electrodes have poor/unknown stability, some have weak electrode coupling, while for some their binding motifs are not well defined. Further binding groups are required to aid molecular design and to achieve a suitable balance in performance across a range of properties. We present an in-depth investigation into the use of carbodithioate esters as contact groups for single-molecule conductance measurements, using scanning tunnelling microscopy break junction measurements (STM-BJ) and detailed surface spectroscopic analysis. We demonstrate that the methyl carbodithioate ester acts as an effective contact for gold electrodes in STM-BJ measurements. Surface enhanced Raman measurements demonstrate that the C=S functionality remains intact when adsorbed on to gold nanoparticles. A gold(I) complex was also synthesised showing a stable C=SâAuI interaction from the ester. Comparison with a benzyl thiomethyl ether demonstrates that the C=S moiety significantly contributes to charge transport in single-molecule junctions. The overall performance of the CS2Me group demonstrates it should be used more extensively and has strong potential for the fabrication of larger area devices with long-term stability.
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BACKGROUND: CEP290-associated inherited retinal degeneration causes severe early-onset vision loss due to pathogenic variants in CEP290. EDIT-101 is a clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) gene-editing complex designed to treat inherited retinal degeneration caused by a specific damaging variant in intron 26 of CEP290 (IVS26 variant). METHODS: We performed a phase 1-2, open-label, single-ascending-dose study in which persons 3 years of age or older with CEP290-associated inherited retinal degeneration caused by a homozygous or compound heterozygous IVS26 variant received a subretinal injection of EDIT-101 in the worse (study) eye. The primary outcome was safety, which included adverse events and dose-limiting toxic effects. Key secondary efficacy outcomes were the change from baseline in the best corrected visual acuity, the retinal sensitivity detected with the use of full-field stimulus testing (FST), the score on the Ora-Visual Navigation Challenge mobility test, and the vision-related quality-of-life score on the National Eye Institute Visual Function Questionnaire-25 (in adults) or the Children's Visual Function Questionnaire (in children). RESULTS: EDIT-101 was injected in 12 adults 17 to 63 years of age (median, 37 years) at a low dose (in 2 participants), an intermediate dose (in 5), or a high dose (in 5) and in 2 children 9 and 14 years of age at the intermediate dose. At baseline, the median best corrected visual acuity in the study eye was 2.4 log10 of the minimum angle of resolution (range, 3.9 to 0.6). No serious adverse events related to the treatment or procedure and no dose-limiting toxic effects were recorded. Six participants had a meaningful improvement from baseline in cone-mediated vision as assessed with the use of FST, of whom 5 had improvement in at least one other key secondary outcome. Nine participants (64%) had a meaningful improvement from baseline in the best corrected visual acuity, the sensitivity to red light as measured with FST, or the score on the mobility test. Six participants had a meaningful improvement from baseline in the vision-related quality-of-life score. CONCLUSIONS: The safety profile and improvements in photoreceptor function after EDIT-101 treatment in this small phase 1-2 study support further research of in vivo CRISPR-Cas9 gene editing to treat inherited retinal degenerations due to the IVS26 variant of CEP290 and other genetic causes. (Funded by Editas Medicine and others; BRILLIANCE ClinicalTrials.gov number, NCT03872479.).
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Antígenos de Neoplasias , Proteínas de Ciclo Celular , Proteínas do Citoesqueleto , Edição de Genes , Degeneração Retiniana , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular/genética , Sistemas CRISPR-Cas , Proteínas do Citoesqueleto/genética , Terapia Genética/efeitos adversos , Injeções Intraoculares , Qualidade de Vida , Retina , Degeneração Retiniana/terapia , Degeneração Retiniana/genética , Acuidade VisualRESUMO
Optical coherence tomography (OCT) and its extension OCT angiography (OCTA) have become essential clinical imaging modalities due to their ability to provide depth-resolved angiographic and tissue structural information non-invasively and at high resolution. Within a field of view, the anatomic detail available is sufficient to identify several structural and vascular pathologies that are clinically relevant for multiple prevalent blinding diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR), and vein occlusions. The main limitation in contemporary OCT devices is that this field of view is limited due to a fundamental trade-off between system resolution/sensitivity, sampling density, and imaging window dimensions. Here, we describe a swept-source OCT device that can capture up to a 12 × 23-mm field of view in a single shot and show that it can identify conventional pathologic features such as non-perfusion areas outside of conventional fields of view. We also show that our approach maintains sensitivity sufficient to visualize novel features, including choriocapillaris morphology beneath the macula and macrophage-like cells at the inner limiting membrane, both of which may have implications for disease.
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Retinopatia Diabética , Vasos Retinianos , Humanos , Vasos Retinianos/patologia , Angiofluoresceinografia , Tomografia de Coerência Óptica/métodos , RetinaRESUMO
BACKGROUND: Background incidence rates (IRs) of health outcomes in Lyme disease endemic regions are useful to contextualize events reported during Lyme disease vaccine clinical trials or post-marketing. The objective of this study was to estimate and compare IRs of health outcomes in Lyme disease endemic versus non-endemic regions in the US during pre-COVID and COVID era timeframes. METHODS: IQVIA PharMetrics® Plus commercial claims database was used to estimate IRs of 64 outcomes relevant to vaccine safety monitoring in the US during January 1, 2017-December 31, 2019 and January 1, 2020-December 31, 2021. Analyses included all individuals aged ≥ 2 years with ≥ 1 year of continuous enrollment. Outcomes were defined by International Classification of Diseases Clinical Modification, 10th Revision (ICD-10-CM) diagnosis codes. IRs and 95 % confidence intervals (CIs) were calculated for each outcome and compared between endemic vs. non-endemic regions, and pre-COVID vs. COVID era using IR ratios (IRR). RESULTS: The study population included 8.7 million (M) in endemic and 27.8 M in non-endemic regions. Mean age and sex were similar in endemic and non-endemic regions. In both study periods, the IRs were statistically higher in endemic regions for anaphylaxis, meningoencephalitis, myocarditis/pericarditis, and rash (including erythema migrans) as compared with non-endemic regions. Conversely, significantly lower IRs were observed in endemic regions for acute kidney injury, disseminated intravascular coagulation, heart failure, myelitis, myopathies, and systemic lupus erythematosus in both study periods. Most outcomes were statistically less frequent during the COVID-era. CONCLUSION: This study identified potential differences between Lyme endemic and non-endemic regions of the US in background IRs of health conditions during pre-COVID and COVID era timeframes to inform Lyme disease vaccine safety monitoring. These regional and temporal differences in background IRs should be considered when contextualizing possible safety signals in clinical trials and post-marketing of a vaccine targeted at Lyme disease prevention.
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Vacinas contra Doença de Lyme , Doença de Lyme , Humanos , Incidência , Doença de Lyme/epidemiologia , Fatores de Risco , Avaliação de Resultados em Cuidados de SaúdeRESUMO
OBJECTIVE: Deep learning classifiers provide the most accurate means of automatically diagnosing diabetic retinopathy (DR) based on optical coherence tomography (OCT) and its angiography (OCTA). The power of these models is attributable in part to the inclusion of hidden layers that provide the complexity required to achieve a desired task. However, hidden layers also render algorithm outputs difficult to interpret. Here we introduce a novel biomarker activation map (BAM) framework based on generative adversarial learning that allows clinicians to verify and understand classifiers' decision-making. METHODS: A data set including 456 macular scans were graded as non-referable or referable DR based on current clinical standards. A DR classifier that was used to evaluate our BAM was first trained based on this data set. The BAM generation framework was designed by combing two U-shaped generators to provide meaningful interpretability to this classifier. The main generator was trained to take referable scans as input and produce an output that would be classified by the classifier as non-referable. The BAM is then constructed as the difference image between the output and input of the main generator. To ensure that the BAM only highlights classifier-utilized biomarkers an assistant generator was trained to do the opposite, producing scans that would be classified as referable by the classifier from non-referable scans. RESULTS: The generated BAMs highlighted known pathologic features including nonperfusion area and retinal fluid. CONCLUSION/SIGNIFICANCE: A fully interpretable classifier based on these highlights could help clinicians better utilize and verify automated DR diagnosis.
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Diabetes Mellitus , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico por imagem , Retina/diagnóstico por imagem , Algoritmos , Angiografia , Tomografia de Coerência Óptica/métodos , BiomarcadoresRESUMO
Purpose: To assess whether the combination of en face OCT and OCT angiography (OCTA) can capture observable, but subtle, structural changes that precede clinically evident retinal neovascularization (RNV) in eyes with diabetic retinopathy (DR). Design: Retrospective, longitudinal study. Participants: Patients with DR that had at least 2 visits. Methods: We obtained wide-field OCTA scans of 1 eye from each participant and generated en face OCT, en face OCTA, and cross-sectional OCTA. We identified eyes with RNV sprouts, defined as epiretinal hyperreflective materials on en face OCT with flow signals breaching the internal limiting membrane on the cross-sectional OCTA without recognizable RNV on en face OCTA and RNV fronds, defined as recognizable abnormal vascular structures on the en face OCTA. We examined the corresponding location from follow-up or previous visits for the presence or progression of the RNV. Main Outcome Measures: The characteristics and longitudinal observation of early signs of RNV. Results: From 71 eyes, we identified RNV in 20 eyes with the combination of OCT and OCTA, of which 13 (65%) were photographically graded as proliferative DR, 6 (30%) severe nonproliferative DR, and 1 (5%) moderate nonproliferative diabetic retinopathy. From these eyes, we identified 38 RNV sprouts and 26 RNV fronds at the baseline. Thirty-four RNVs (53%) originated from veins, 24 (38%) were from intraretinal microabnormalities, and 6 (9%) were from a nondilated capillary bed. At the final visit, 53 RNV sprouts and 30 RNV fronds were detected. Ten eyes (50%) showed progression, defined as having a new RNV lesion or the development of an RNV frond from an RNV sprout. Four (11%) RNV sprouts developed into RNV fronds with a mean interval of 7.0 months. Nineteen new RNV sprouts developed during the follow-up, whereas no new RNV frond was observed outside an identified RNV sprout. The eyes with progression were of younger age (P = 0.014) and tended to be treatment naive (P = 0.07) compared with eyes without progression. Conclusions: Longitudinal observation demonstrated that a combination of en face OCT and cross-sectional OCTA can identify an earlier form of RNV before it can be recognized on en face OCTA. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) are promising candidates for cell-based therapy for several immune-mediated inflammatory diseases (IMIDs) due to their multiplicity of immunomodulatory and reparative properties and favorable safety profile. However, although preclinical data were encouraging, the clinical benefit demonstrated in clinical trials of autologous MSC transplantation in a number of conditions has been less robust. This may be explained by the growing body of evidence pointing to abnormalities of the bone marrow microenvironment in IMIDs, including impaired MSC function. However, it is not currently known whether these abnormalities arise as a cause or consequence of disease, the role they play in disease initiation and/or progression, or whether they themselves are targets for disease modification. Here, we review current knowledge about the function of the BM microenvironment in IMIDs including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and type I diabetes, focusing on MSCs in particular. We predict that an improved understanding of disease-related changes in the bone marrow microenvironment including the role of MSCs in vivo, will yield new insights into pathophysiology and aid identification of new drug targets and optimization of cell-based therapy in IMIDs.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Medula Óssea , Células da Medula Óssea , Agentes de Imunomodulação , Células-Tronco Mesenquimais/fisiologia , Transplante Autólogo , HumanosRESUMO
IMPORTANCE: Methamphetamine use is a growing public health concern nationwide. Suicide is the second leading cause of death in 2019 for US citizens aged 10-14 years and 25-34 years and is also a significant public health concern. Understanding the intersection of methamphetamine use and suicidal ideation (SI) is necessary to develop public health and policy solutions that mitigate these ongoing severe public health issues. OBJECTIVE: Our objective was to examine SI in methamphetamine users to allow us to determine prevalence and trends by age, sex, race, and geographical region. DESIGN, SETTINGS, AND PARTICIPANTS: Using data collected between 2008 and 2019 from the National Inpatient Sample (NIS) database, we identified hospital admissions (HA) of patients ≥18 years of age with a primary or secondary diagnosis of SI who were also diagnosed as methamphetamine users. Those who used other substances with methamphetamine were excluded from the analysis. MAIN OUTCOME AND MEASURES: To determine the trend and prevalence of hospital admissions due to SI and SI among methamphetamine users, we used trend weights to calculate the national estimates and performed design-based analysis to account for complex survey design and sampling weights on data collected between 2008 and 2019 in the US. RESULTS: The prevalence ratio (PR) of hospitalizations with concurrent SI and methamphetamine use increased 16-fold from 2008 to 2019. The most significant increase occurred between 2015 and 2016; the PR doubled from 6.07 to 12.14. The PR of hospitalizations with concurrent SI and methamphetamine use was highest in patients aged 26-40 (49.08%) and 41-64 (28.49%). Patients aged 41-64 showed the most significant increase from 2008 to 2019 (15.8-fold). While non-Hispanic White patients comprised most of these hospitalizations (77.02%), non-Hispanic Black patients showed the highest proportional increase (39.1-fold). The Southern and Western regions in the US showed the highest PR for these hospitalizations (34.86% and 34.31%, respectively). CONCLUSION AND RELEVANCE: Our findings indicate that SI in methamphetamine users has been increasing for some time and is likely to grow. In addition, our results suggest that these patients are demographically different. Both conditions are associated with a lesser likelihood of seeking and receiving care. Therefore, when addressing increased SI or methamphetamine use, learning more about patients who share both conditions is necessary to ensure proper care.
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Metanfetamina , Suicídio , Humanos , Estados Unidos/epidemiologia , Adolescente , Ideação Suicida , Metanfetamina/efeitos adversos , Etnicidade , Estudos Longitudinais , PrevalênciaRESUMO
BACKGROUND: Atrial fibrillation (AF) is a common comorbidity in patients with heart failure with preserved ejection fraction (HFpEF) and in heart failure with mildly reduced ejection fraction (HFmrEF). OBJECTIVES: This study sought to describe AF burden and its clinical impact among individuals with HFpEF and HFmrEF who participated in a randomized clinical trial of atrial shunt therapy (REDUCE LAP-HF II [A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure]) and to evaluate the effect of atrial shunt therapy on AF burden. METHODS: Study investigators characterized AF burden among patients in the REDUCE LAP-HF II trial by using ambulatory cardiac patch monitoring at baseline (median patch wear time, 6 days) and over a 12-month follow-up (median patch wear time, 125 days). The investigators determined the association of baseline AF burden with long-term clinical events and examined the effect of atrial shunt therapy on AF burden over time. RESULTS: Among 367 patients with cardiac monitoring data at baseline and follow-up, 194 (53%) had a history of AF or atrial flutter (AFL), and median baseline AF burden was 0.012% (IQR: 0%-1.3%). After multivariable adjustment, baseline AF burden ≥0.012% was significantly associated with heart failure (HF) events (HR: 2.00; 95% CI: 1.17-3.44; P = 0.01) both with and without a history of AF or AFL (P for interaction = 0.68). Adjustment for left atrial reservoir strain attenuated the baseline AF burden-HF event association (HR: 1.71; 95% CI: 0.93-3.14; P = 0.08). Of the 367 patients, 141 (38%) had patch-detected AF during follow-up without a history of AF or AFL. Atrial shunt therapy did not change AF incidence or burden during follow-up. CONCLUSIONS: In HFpEF and HFmrEF, nearly 40% of patients have subclinical AF by 1 year. Baseline AF burden, even at low levels, is associated with HF events. Atrial shunt therapy does not affect AF incidence or burden. (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients with Heart Failure [REDUCE LAP-HF II]; NCT03088033).
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Fibrilação Atrial , Insuficiência Cardíaca , Humanos , Fibrilação Atrial/epidemiologia , Volume Sistólico , Átrios do Coração , Implantação de Prótese , PrognósticoRESUMO
Mental stress is a risk factor for myocardial infarction in women. The central hypothesis of this study is that restraint stress induces sex-specific changes in gene expression in the heart, which leads to an intensified response to ischemia/reperfusion injury due to the development of a pro-oxidative environment in female hearts. We challenged male and female C57BL/6 mice in a restraint stress model to mimic the effects of mental stress. Exposure to restraint stress led to sex differences in the expression of genes involved in cardiac hypertrophy, inflammation, and iron-dependent cell death (ferroptosis). Among those genes, we identified tumor protein p53 and cyclin-dependent kinase inhibitor 1A (p21), which have established controversial roles in ferroptosis. The exacerbated response to I/R injury in restraint-stressed females correlated with downregulation of p53 and nuclear factor erythroid 2-related factor 2 (Nrf2, a master regulator of the antioxidant response system-ARE). S-female hearts also showed increased superoxide levels, lipid peroxidation, and prostaglandin-endoperoxide synthase 2 (Ptgs2) expression (a hallmark of ferroptosis) compared with those of their male counterparts. Our study is the first to test the sex-specific impact of restraint stress on the heart in the setting of I/R and its outcome.
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Traumatismos Cardíacos , Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Camundongos , Feminino , Masculino , Animais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Estresse Oxidativo , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/genética , Expressão Gênica , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
PURPOSE: To report a case of paracentral acute middle maculopathy as the earliest sign of an undiagnosed, life-threatening hyperviscosity syndrome. METHODS: A 78-year-old man with an acute paracentral scotoma and examination findings of bilateral arteriolar tortuosity and unilateral paracentral acute middle maculopathy. RESULTS: Work-up revealed anemia and elevated serum viscosity. Protein electrophoresis demonstrated an immunoglobulin M kappa monoclonal protein spike, and bone marrow biopsy confirmed an immunoglobulin M gammopathy consistent with Waldenström macroglobulinemia. Systemic chemotherapy was initiated. CONCLUSION: This case demonstrates typical optical coherence tomography findings of paracentral acute middle maculopathy, which led to the diagnosis of a rare lymphoproliferative disorder. This highlights the importance of a prompt work-up for paracentral acute middle maculopathy to detect underlying systemic diseases, including hyperviscosity syndromes.
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Degeneração Macular , Doenças Retinianas , Macroglobulinemia de Waldenstrom , Masculino , Humanos , Idoso , Angiofluoresceinografia/métodos , Doenças Retinianas/diagnóstico , Doenças Retinianas/etiologia , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Tomografia de Coerência Óptica/métodos , Doença AgudaRESUMO
Projection artifacts are a significant limitation of optical coherence tomographic angiography (OCTA). Existing techniques to suppress these artifacts are sensitive to image quality, becoming less reliable on low-quality images. In this study, we propose a novel signal attenuation-compensated projection-resolved OCTA (sacPR-OCTA) algorithm. In addition to removing projection artifacts, our method compensates for shadows beneath large vessels. The proposed sacPR-OCTA algorithm improves vascular continuity, reduces the similarity of vascular patterns in different plexuses, and removes more residual artifacts compared to existing methods. In addition, the sacPR-OCTA algorithm better preserves flow signal in choroidal neovascular lesions and shadow-affected areas. Because sacPR-OCTA processes the data along normalized A-lines, it provides a general solution for removing projection artifacts agnostic to the platform.
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Patellar fracture and dental anomaly syndrome (PADS) is a congenital bone disease of cats that is characterized by atraumatic bone fractures (most commonly the patella), the persistence of deciduous teeth, and impaction of permanent teeth. Jaw swelling due to osteomyelitis is often the reason that cats with PADS are presented for veterinary dental care. The clinical history, oral examination findings, dental radiological findings, and histopathology were evaluated for 13 cats with dental and skeletal pathology consistent with PADS, including 9 with osteomyelitis. Cats in this study were predominantly domestic shorthair (12 of 13 cats), and there was no apparent sex predilection. All cats had multiple persistent deciduous teeth and multiple impacted permanent teeth, although the number of persistent and impacted teeth varied. Osteomyelitis of the jaw typically occurred within the first 4 years of life. Osteomyelitis of the mandible was 4 times more common than osteomyelitis of the maxilla. Histologically, osteomyelitis was chronic, neutrophilic, and osteoproliferative. Necrotic bone was confirmed in 67% of osteomyelitis lesions. Histological evaluation of jaws without inflammation demonstrated abnormal amounts of unmodeled bone, abnormally dense bone, and retention of cartilage in the caudal mandible. Three cats in the study had mandibular distoclusion and 2 had concurrent paronychia. To obtain a favorable clinical outcome in PADS cats with jaw swelling, prompt and aggressive surgical treatment of osteomyelitis is required. Extraction of persistent deciduous teeth and impacted permanent teeth is recommended when there is associated periodontitis or osteomyelitis.
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Doenças do Gato , Fraturas Ósseas , Osteomielite , Dente Impactado , Gatos , Animais , Patologia Bucal , Fraturas Ósseas/patologia , Fraturas Ósseas/veterinária , Dente Impactado/veterinária , Maxila/patologia , Osteomielite/veterinária , Doenças do Gato/patologiaRESUMO
Introduction: To assess the diagnostic accuracy of automatically quantified macular fluid volume (MFV) for treatment-required diabetic macular edema (DME). Methods: This retrospective cross-sectional study included eyes with DME. The commercial software on optical coherence tomography (OCT) produced the central subfield thickness (CST), and a custom deep-learning algorithm automatically segmented the fluid cysts and quantified the MFV from the volumetric scans of an OCT angiography system. Retina specialists treated patients per standard of care based on clinical and OCT findings without access to the MFV. The main outcome measures were the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity of the CST, MFV, and visual acuity (VA) for treatment indication. Results: Of 139 eyes, 39 (28%) were treated for DME during the study period and 101 (72%) were previously treated. The algorithm detected fluid in all eyes; however, only 54 eyes (39%) met the DRCR.net criteria for center-involved ME. The AUROC of MFV predicting a treatment decision of 0.81 was greater than that of CST (0.67) (P = .0048). Untreated eyes that met the optimal threshold for treatment-required DME based on MFV (>0.031 mm3) had better VA than treated eyes (P = .0053). A multivariate logistic regression model showed that MFV (P = .0008) and VA (P = .0061) were significantly associated with a treatment decision, but CST was not. Conclusions: MFV had a higher correlation with the need for treatment for DME than CST and may be especially useful for ongoing management of DME.