RESUMEN
Antithrombotic treatment in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) poses a dilemma. We compared outcomes of dual thrombotic therapy (DAT) (direct oral anticoagulants [DOACs]/warfarin + antiplatelets) versus triple antithrombotic therapy (TAT) (DOACs/warfarin, aspirin, and P2Y12 inhibitor) in this population. Multiple databases were searched from inception to 12/17/2023 to identify randomized controlled trials (RCTs) comparing DAT versus TAT in patients with AF and ACS. Outcomes included major adverse cardiac events (MACE), bleeding events, stroke, stent thrombosis, and myocardial infarction (MI). Relative risk (RR) and 95% confidence intervals were estimated with a random-effects model using the inverse-variance technique. We assigned I2>50% as an indicator of statistical heterogeneity. P-value <0.05 was considered significant. Ten RCTs comprising 6186 patients on TAT (female 26%, mean age 71±9 yrs) and 6,800 patients on DAT (female 27%, mean age 71±9 yrs) were included. Patients receiving DAT experienced lower rates of bleeding events compared to those receiving TAT, with relative risks of 0.69 [0.55-0.87] (p<0.001), 0.65 [0.40-1.06] (p=0.09), and 0.62 [0.46-0.84] (p<0.001) for TAT durations of 3, 6, and 12 months, respectively. No difference was seen in the occurrence of MACE, MI, stroke, or stent thrombosis between DAT and TAT across all 3 durations of TAT therapy. This is the largest pooled analysis comparing TAT to DAT stratified by duration of antithrombotic therapy. Our results revealed that DAT was associated with reduced bleeding risk despite no difference in other outcomes.
RESUMEN
Background: While patients with spontaneous coronary artery dissection (SCAD) occasionally present with concurrent ventricular arrhythmias (VA), the impact of VA on in-hospital outcomes in the United States (US) is not well-established. This study aims to analyze in-hospital outcomes of patients with SCAD and concurrent VA and to determine the factors associated with VA occurrence in this high-risk population in the US. Methods: Using the Nationwide Readmissions Database, our study included patients age 18 years or older who had SCAD between 2017 and 2020. We categorized the cohort into 2 groups depending on the presence of VA during hospitalization. In-hospital outcomes were assessed between SCAD patients with VA and those without. Weighted analysis was performed. We analyzed the independent factors associated with VA occurring among SCAD patients through univariable and multivariable analyses. Results: Eight hundred seventy-seven SCAD patients were included in the study: 118 (13.5%) with VA and 759 (86.6%) without. SCAD patients with concurrent VA were associated with higher rates of early mortality (10.2% vs 2.0%; P < .01), prolonged index hospital stay (≥7 days) (33.1% vs 11.7%; P < .01), and non-home discharge (21.2% vs 5.9%; P < .01). The length of hospital stay was longer in the SCAD with concurrent VA group (7.39 days vs 3.58 days; P < .01), and the median cumulative cost of hospitalization was also higher in this group ($31,451 vs $13,802; P < .01). SCAD patients with concurrent VA had increased in-hospital adverse events: acute heart failure, cardiac arrest, cardiogenic shock, cerebral infarction, pulmonary edema, and acute kidney injury. In multivariable analysis, the independent factors associated with VA occurrence among SCAD patients were chronic liver disease (aOR, 3.42; 95% CI, 1.43-8.20; P < .01) and heart failure (aOR, 5.63; 95% CI, 3.36-9.42; P < .01). Conclusions: Concurrence of VA among SCAD patients was associated with poorer in-hospital outcomes. Heart failure and chronic liver disease were the independent factors associated with VA occurrence in SCAD patients.
RESUMEN
Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly associated with insulin resistance development. Hepatic lipid accumulation and inflammation are considered the main drivers of hepatic insulin resistance in MASLD. Cysteine-rich 61 (Cyr61 also called CCN1), a novel secretory matricellular protein, is implicated in liver inflammation, and its role in MASLD is not clearly understood. Therefore, we investigated the role of Cyr61 in hepatic insulin resistance and lipid metabolism as major factors in MASLD pathogenesis. In high-fat diet (HFD)-fed C57BL/6J mice, Cyr61 was downregulated or upregulated via viral transduction. Measurements of glucose homeostasis, histological assessment of liver tissues, and gene expression and signaling pathways of lipogenesis, fatty acid oxidation, and inflammation were performed using liver samples from these mice. Cyr61 levels in HepG2 cells were reduced using RNAi-mediated gene knockdown. Inflammation and insulin resistance were evaluated using real-time polymerase chain reaction and western blotting. HFD/AAV-shCyr61 mice exhibited enhanced glucose tolerance via the protein kinase B pathway, reduced hepatic inflammation, decreased lipogenesis, and increased fatty acid oxidation. Notably, HFD/AAV-shCyr61 mice showed elevated protein expression of sirtuin 6 and phosphorylated-AMP-activated protein kinase. In vitro experiments demonstrated that inhibition of Cyr61 downregulated pro-inflammatory cytokines such as interleukin-1 beta, IL-6, and tumor necrosis factor-alpha via the nuclear factor kappa B/c-Jun N-terminal kinase pathway, and alleviated insulin resistance. Cyr61 affected hepatic inflammation, lipid metabolism, and insulin resistance. Inhibition of Cyr61 reduced inflammation, recovered insulin resistance, and altered lipid metabolism in vivo and in vitro. Therefore, Cyr61 is a potential therapeutic target in MASLD.
Asunto(s)
Proteína 61 Rica en Cisteína , Dieta Alta en Grasa , Resistencia a la Insulina , Metabolismo de los Lípidos , Hígado , Ratones Endogámicos C57BL , Animales , Proteína 61 Rica en Cisteína/metabolismo , Proteína 61 Rica en Cisteína/genética , Células Hep G2 , Humanos , Ratones , Dieta Alta en Grasa/efectos adversos , Masculino , Hígado/metabolismo , LipogénesisRESUMEN
PURPOSE: Few studies have investigated the association between smoking and microvascular complications in the Asian population with type 2 diabetes mellitus (T2DM). We aimed to investigate the relationship between smoking status and microvascular complications in Korean patients with T2DM. MATERIALS AND METHODS: From the Korean National Diabetes Program cohort, we included 2316 Korean male with T2DM who had baseline clinical information available, including their smoking status, and underwent diabetic complication studies. RESULTS: Compared to non-smokers, current smokers had higher odds of any-microvascular complications [adjusted odds ratio (aOR) 1.45, 95% confidence interval (CI) 1.07-1.97, p=0.016]. The odds of neuropathy were significantly higher; however, the odds of retinopathy were significantly lower in current smokers than in nonsmokers (all p<0.05). Among those who underwent repeated complication tests after 3 years, the risk of newly developed retinopathy was significantly increased in ex-smokers [aOR 3.77 (95% CI 1.61-8.87), p=0.002]. Within ex-smokers, long smoking duration and smoking cessation within the recent 5 years were associated with an increased risk of newly developed retinopathy (all p<0.05). CONCLUSION: Male smokers had higher odds of having overall diabetic microvascular complications, including neuropathy. However, the odds of having retinopathy were significantly lower among current smokers. More attention and research are needed regarding the increased risk of retinopathy development in ex-smokers who have recently stopped smoking after a long history of smoking.
Asunto(s)
Diabetes Mellitus Tipo 2 , Retinopatía Diabética , Fumar , Humanos , Masculino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Persona de Mediana Edad , República de Corea/epidemiología , Fumar/efectos adversos , Retinopatía Diabética/epidemiología , Retinopatía Diabética/etiología , Anciano , Angiopatías Diabéticas/epidemiología , Factores de Riesgo , Oportunidad Relativa , Neuropatías Diabéticas/epidemiología , Neuropatías Diabéticas/etiología , AdultoRESUMEN
BACKGROUND: Although myocardial infarction with nonobstructive coronary arteries (MINOCA) is more common in women, it is unknown whether sex is a risk factor for adverse outcomes in patients with MINOCA. We aimed to investigate the relationship between sex differences and outcomes of patients with MINOCA. METHODS AND RESULTS: A systematic literature search was performed in PubMed, Embase, and Cochrane databases from their inception until August 2023 for relevant studies. End points were pooled using the Hartung-Knapp-Sidik-Jonkman random-effects model as odds ratio (OR) with 95% CIs. Nine studies, involving 30 281 patients with MINOCA (comprising 18 079 women and 12 202 men), were included in the study. Women were older and had a higher prevalence of hypertension, diabetes, and stroke compared with men. The median duration of follow-up was 3.5 years, with an interquartile range of 2.2 to 4.2 years. Pooled analysis revealed no statistically significant difference in the risk of all-cause mortality (OR, 1.03 [95% CI, 0.87-1.22]), major adverse cardiovascular events (OR, 1.18 [95% CI, 0.89-1.58]), heart failure (OR, 1.32 [95% CI, 0.57-3.03]), stroke (OR, 1.13 [95% CI, 0.56-2.26]), and myocardial infarction (OR, 1.04 [95% CI, 0.29-3.76]) between the 2 groups. Regarding short-term outcomes, women had a significantly higher risk of in-hospital major adverse cardiovascular events compared with men (OR, 1.33 [95% CI, 1.16-1.53]) whereas there was no significant difference in the risk of in-hospital mortality (OR, 0.90 [95% CI, 0.64-1.28]) between the 2 patient groups. CONCLUSIONS: Despite the differences in demographics and comorbidity profiles, there was no significant difference in the long-term outcomes for patients with MINOCA between sexes. However, it is noteworthy that women experienced a higher risk of in-hospital major adverse cardiovascular events compared with men.
Asunto(s)
Infarto del Miocardio , Humanos , Femenino , Masculino , Factores Sexuales , Factores de Riesgo , Infarto del Miocardio/epidemiología , Infarto del Miocardio/mortalidad , Medición de Riesgo , MINOCA/epidemiología , MINOCA/complicaciones , Persona de Mediana EdadRESUMEN
This research group (FROM) aimed to develop biomarkers for exposure to environmental hazards and diseases, assess environmental diseases, and apply and verify these biomarkers in environmentally vulnerable areas. Environmentally vulnerable areasincluding refineries, abandoned metal mines, coal-fired power plants, waste incinerators, cement factories, and areas with high exposure to particulate matteralong with control areas, were selected for epidemiological investigations. A total of 1,157 adults, who had resided in these areas for over 10 years, were recruited between June 2021 and September 2023. Personal characteristics of the study participants were gathered through a survey. Biological samples, specifically blood and urine, were collected during the field investigations, separated under refrigerated conditions, and then transported to the laboratory for biomarker analysis. Analyses of heavy metals, environmental hazards, and adducts were conducted on these blood and urine samples. Additionally, omics analyses of epigenomes, proteomes, and metabolomes were performed using the blood samples. The biomarkers identified in this study will be utilized to assess the risk of environmental disease occurrence and to evaluate the impact on the health of residents in environmentally vulnerable areas, following the validation of diagnostic accuracy for these diseases.
RESUMEN
PURPOSE OF REVIEW: Cardiac Allograft vasculopathy (CAV) is a major barrier to improving outcomes after heart transplantation. Coronary angiography has very low sensitivity to detect early CAV and intravascular ultrasound (IVUS) only improves it to some extent. In this article, we detail the current evidence surrounding use of Optical Coherence tomography (OCT) in patients with CAV. RECENT FINDINGS: OCT has the ability to recognize CAV at earlier stages with intimal thickness < 150 µm, can characterize CAV in almost pathologic / microscopic detail - plaque characteristics are better visualized and novel early features such as layered fibrotic plaques and microchannels have been identified. Progression of CAV can be monitored also, with promise shown in automated serial measurements also. OCT has significantly advanced our understanding of the pathophysiology-as well as permits precise monitoring and surveillance of the disease. Potential treatment options could also be evaluated using OCT.
Asunto(s)
Aloinjertos , Enfermedad de la Arteria Coronaria , Trasplante de Corazón , Tomografía de Coherencia Óptica , Humanos , Trasplante de Corazón/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Ultrasonografía IntervencionalRESUMEN
Importance: Data are limited regarding the effects of intravascular imaging guidance during complex percutaneous coronary intervention (PCI) in patients with diabetes. Objective: To compare the clinical outcomes of intravascular imaging-guided vs angiography-guided complex PCI in patients with or without diabetes. Design, Setting, and Participants: This prespecified secondary analysis of a subgroup of patients in RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention), an investigator-initiated, open-label multicenter trial, analyzed enrolled patients who underwent complex PCI at 20 sites in Korea from May 2018 through May 2021. Eligible patients were randomly assigned in a 2:1 ratio to undergo either the intravascular imaging-guided PCI or angiography-guided PCI. Data analyses were performed from June 2023 to April 2024. Interventions: Percutaneous coronary intervention was performed either under the guidance of intravascular imaging or angiography alone. Main Outcomes and Measures: The primary end point was target vessel failure (TVF), defined as a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. Results: Among the 1639 patients included in the analysis (mean [SD] age, 65.6 [10.2] years; 1300 males [79.3%]), 617 (37.6%) had diabetes. The incidence of TVF was significantly higher in patients with diabetes than patients without diabetes (hazard ratio [HR], 1.86; 95% CI, 1.33-2.60; P < .001). Among patients without diabetes, the intravascular imaging-guided PCI group had a significantly lower incidence of TVF compared with the angiography-guided PCI group (4.7% vs 12.2%; HR, 0.41 [95% CI, 0.25-0.67]; P < .001). Conversely, in patients with diabetes, the risk of TVF was not significantly different between the 2 groups (12.9% vs 12.3%; HR, 0.97 [95% CI, 0.60-1.57]; P = .90). There was a significant interaction between the use of intravascular imaging and diabetes for the risk of TVF (P for interaction = .02). Among patients with diabetes, only those with good glycemic control (hemoglobin A1c level ≤7.5%) and who achieved stent optimization by intravascular imaging showed a lower risk of future ischemic events (HR, 0.31; 95% CI, 0.12-0.82; P = .02). Conclusions and Relevance: In this secondary analysis of a subgroup of patients in the RENOVATE-COMPLEX-PCI trial, intravascular imaging guidance reduced the risk of TVF compared with angiography guidance in patients without diabetes (but not in patients with diabetes) during complex PCI. In patients with diabetes undergoing complex PCI, attention should be paid to stent optimization using intravascular imaging and glycemic control to improve outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.
Asunto(s)
Angiografía Coronaria , Intervención Coronaria Percutánea , Humanos , Intervención Coronaria Percutánea/métodos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Angiografía Coronaria/métodos , Diabetes Mellitus , República de Corea , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief, as well as the neural responses within spinal pain circuits, remain largely unexplored. In this study, using a novel preparation, we investigated the impact of varying kilohertz frequency SCS on dorsal horn neuron activation. Employing calcium imaging on isolated spinal cord slices, we found that extracellular electric fields at kilohertz frequencies (1, 3, 5, 8, and 10 kHz) induce distinct patterns of activation in dorsal horn neurons. Notably, as the frequency of extracellular electric fields increased, there was a clear and significant monotonic escalation in neuronal activity. This phenomenon was observed not only in superficial dorsal horn neurons, but also in those located deeper within the dorsal horn. Our study demonstrates the unique patterns of dorsal horn neuron activation in response to varying kilohertz frequencies of extracellular electric fields, and we contribute to a deeper understanding of how kHF-SCS induces paresthesia-free pain relief. Furthermore, our study highlights the potential for kHF-SCS to modulate sensory information processing within spinal pain circuits. These insights pave the way for future research aimed at optimizing kHF-SCS parameters and refining its therapeutic applications in the clinical management of chronic pain.
RESUMEN
AIM: Lipoprotein(a) [Lp(a)] has demonstrated its association with atherosclerosis and myocardial infarction. However, its role in the development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is not clearly established. The aim of this study is to investigate the association between Lp(a) and ISR. METHODS: A retrospective study of adult patients who underwent successful PCI between January 2006 and December 2017 at the three Mayo Clinic sites and had a preprocedural Lp(a) measurement was conducted. Patients were divided into two groups according to the serum Lp(a) concentration (high Lp(a) ≥50 mg/dl and low Lp(a) <50 mg/dl). Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) versus those with low Lp(a). RESULTS: A total of 1209 patients were included, with mean age 65.9 ±11.7 years and 71.8% were male. Median follow-up after baseline PCI was 8.8 (IQR 7.4) years. Restenosis was observed in 162 (13.4%) patients. Median serum levels of Lp(a) were significantly higher in patients affected by ISR versus non-affected cases: 27 (IQR 73.8) vs. 20 (IQR 57.5) mg/dL, p=0.008. The rate of ISR was significantly higher among patients with high Lp(a) versus patients with low Lp(a) values (17.0% vs 11.6%, p=0.010). High Lp(a) values were independently associated with ISR events (HR 1.67, 95%CI 1.18 to 2.37, p=0.004), and this association was more prominent after the first year following the PCI. CONCLUSION: Lipoprotein(a) is an independent predictor for long-term in-stent restenosis and should be considered in the evaluation of patients undergoing PCI.
The role of Lp(a) in the development of in-stent restenosis is not clearly established. In this study including 1209 patients who underwent successful percutaneous coronary intervention and had a preprocedural Lp(a) measurement between 2006 and 2017, the rates of restenosis were significantly higher among patients with high Lp(a) versus patients with low Lp(a) values and high Lp(a) concentrations were independently associated with restenosis events. Lp(a) should be considered as a risk factor for long term in-stent restenosis in the evaluation of patients undergoing percutaneous coronary intervention and assessed as a potential therapeutic target for reducing residual cardiovascular risk in this population.
RESUMEN
INTRODUCTION: Disparities in stroke outcomes, influenced by the use of systemic thrombolysis, endovascular therapies, and rehabilitation services, have been identified. Our study assesses these disparities in mortality after stroke between rural and urban areas across the United States (US). METHODS: We analyzed the CDC data on deaths attributed to cerebrovascular disease from 1999 to 2020. Data was categorized into rural and urban regions for comparative purposes. Age-adjusted mortality rates (AAMR) were computed using the direct method, allowing us to examine the ratios of rural to urban deaths for the cumulative population and among demographic subpopulations. Linear regression models were used to assess temporal changes in mortality ratios over the study period, yielding beta-coefficients (ß). RESULTS: There was a total of 628,309 stroke deaths in rural regions and 2,556,293 stroke deaths within urban regions. There were 1.13 rural deaths for each one urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.41). The rural-urban mortality ratio in Hispanic populations decreased from 1.32 rural deaths for each urban death per 100,000 population in 1999 to 0.85 in 2020 (ß = -0.011, ptrend < 0.001). For non-Hispanic populations, mortality remained stagnant with 1.12 rural deaths for each urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.543). Regionally, the Southern US exhibited the highest disparity with a urban-rural mortality ratio of 1.19, followed by the Northeast (1.13), Midwest (1.04), and West (1.01). CONCLUSIONS: Our findings depict marked disparities in stroke mortality between rural and urban regions, emphasizing the importance of targeted interventions to mitigate stroke-related disparities.
Asunto(s)
Disparidades en el Estado de Salud , Salud Rural , Accidente Cerebrovascular , Salud Urbana , Humanos , Estados Unidos/epidemiología , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/diagnóstico , Femenino , Masculino , Anciano , Persona de Mediana Edad , Factores de Riesgo , Factores de Tiempo , Disparidades en Atención de Salud , Anciano de 80 o más Años , Hispánicos o Latinos , Adulto , Bases de Datos Factuales , Factores Raciales , Causas de MuerteRESUMEN
BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).
Asunto(s)
Síndrome Coronario Agudo , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Stents , Humanos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Enfermedad de la Arteria Coronaria/mortalidad , Factores de Tiempo , Factores de Riesgo , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Ultrasonografía Intervencional , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/etiología , Enfermedad CrónicaRESUMEN
The escalating global threat of infectious diseases, including monkeypox virus (MPXV), necessitates advancements in point-of-care diagnostics, moving beyond the constraints of conventional methods tethered to centralized laboratories. Here, we introduce multiple CRISPR RNA (crRNA)-based biosensors that can directly detect MPXV within 35 minutes without pre-amplification, leveraging the enhanced sensitivity and antifouling attributes of the BSA-based nanocomposite. Multiple crRNAs, strategically targeting diverse regions of the F3L gene of MPXV, are designed and combined to amplify Cas12a activation and its collateral cleavage of reporter probes. Notably, our electrochemical sensors exhibit the detection limit of 669 fM F3L gene without amplification, which is approximately a 15-fold improvement compared to fluorescence detection. This sensor also shows negligible changes in peak current after exposure to complex biological fluids, such as whole blood and serum, maintaining its sensitivity at 682 fM. This sensitivity is nearly identical to the conditions when only the F3L gene was present in PBS. In summary, our CRISPR-based electrochemical biosensors can be utilized as a high-performance diagnostic tool in resource-limited settings, representing a transformative leap forward in point-of-care testing. Beyond infectious diseases, the implications of this technology extend to various molecular diagnostics, establishing itself as a rapid, accurate, and versatile platform for detection of target analytes.
Asunto(s)
Técnicas Biosensibles , Sistemas CRISPR-Cas , Técnicas Electroquímicas , Nanocompuestos , Técnicas Biosensibles/métodos , Nanocompuestos/química , Técnicas Electroquímicas/métodos , Humanos , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Asociadas a CRISPR/genética , Límite de Detección , Proteínas Bacterianas/genética , Animales , Endodesoxirribonucleasas/metabolismo , Incrustaciones Biológicas/prevención & controlRESUMEN
Background and Objectives: Real-world clinical data, outside of clinical trials and expert centers, on adverse events related to the use of SyncCardia total artificial heart (TAH) remain limited. We aim to analyze adverse events related to the use of SynCardia TAH reported to the Food and Drug Administration (FDA)'s Manufacturers and User Defined Experience (MAUDE) database. Methods: We reviewed the FDA's MAUDE database for any adverse events involving the use of SynCardia TAH from 1/01/2012 to 9/30/2020. All the events were independently reviewed by three physicians. Results: A total of 1,512 adverse events were identified in 453 "injury and death" reports in the MAUDE database. The most common adverse events reported were infection (20.2%) and device malfunction (20.1%). These were followed by bleeding events (16.5%), respiratory failure (10.1%), cerebrovascular accident (CVA)/other neurological dysfunction (8.7%), renal dysfunction (7.5%), hepatic dysfunction (2.2%), thromboembolic events (1.8%), pericardial effusion (1.8%), and hemolysis (1%). Death was reported in 49.4% of all the reported cases (n=224/453). The most common cause of death was multiorgan failure (n=73, 32.6%), followed by CVA/other non-specific neurological dysfunction (n=44, 19.7%), sepsis (n=24, 10.7%), withdrawal of support (n=20, 8.9%), device malfunction (n=11, 4.9%), bleeding (n=7, 3.1%), respiratory failure (n=7, 3.1%), gastrointestinal disorder (n=6, 2.7%), and cardiomyopathy (n=3, 1.3%). Conclusions: Infection was the most common adverse event following the implantation of TAH. Most of the deaths reported were due to multiorgan failure. Early recognition and management of any possible adverse events after the TAH implantation are essential to improve the procedural outcome and patient survival.
RESUMEN
BACKGROUND: Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real-world mortality data on valvular heart disease (VHD) in the United States remain limited. METHODS AND RESULTS: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age-adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22-year study, there were 446 096 VHD deaths, accounting for 0.80% of all-cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD-related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2-8.5) to 6.6 (95% CI, 6.5-6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. CONCLUSIONS: The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.
Asunto(s)
Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Enfermedades de las Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Estenosis de la Válvula Mitral , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Adolescente , Enfermedades de las Válvulas Cardíacas/epidemiologíaRESUMEN
Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.
Asunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Humanos , Masculino , Intervención Coronaria Percutánea/métodos , Femenino , Anciano , Persona de Mediana Edad , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Factores Sexuales , Ultrasonografía Intervencional/métodosRESUMEN
OBJECTIVE: We aimed to investigate risk factors for the recurrence of distal anterior cerebral artery (DACA) aneurysms after endovascular treatment (EVT). METHODS: The clinical and radiologic outcomes of DACA aneurysms treated with endovascular methods at a single tertiary hospital from September 2008 to December 2021 were retrospectively reviewed. We measured the angle between 2 distal branches of DACA aneurysms and categorized the angle as follows: 1) wide-angle (≥180°), and 2) narrow-angle type configuration (<180°). Univariate and multivariate analyses were performed to demonstrate the relationships between characteristics of DACA aneurysm and recurrence risk. RESULTS: In total, 132 DACA aneurysms were treated in our institution. Among these, 47 DACA aneurysms after EVT were included in this study. Forty patients underwent coil embolization without stent, 7 for stent-assisted coil embolization. At the last follow-up (mean 30.2 ± 24.2 months), overall recurrence rate was 23.4% (n = 11). Recurrence rate of the wide-angle type (9 of 23, 39.1%) was significantly greater than narrow-angle type (2 of 24, 8.3%) (P = 0.041; odds ratio 8.174, 95% confidence interval 1.094-61.066). Irregular shape of the DACA aneurysm also showed significantly greater recurrence rate (P = 0.011; odds ratio 10.663, 95% confidence interval 1.701-66.838) after endovascular treatment. CONCLUSIONS: The wide-angle between 2 distal branches of DACA aneurysm and irregular shape might be independent risk factors for the recurrence after endovascular treatment for DACA aneurysms.
Asunto(s)
Embolización Terapéutica , Procedimientos Endovasculares , Aneurisma Intracraneal , Recurrencia , Humanos , Femenino , Masculino , Aneurisma Intracraneal/cirugía , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/terapia , Persona de Mediana Edad , Factores de Riesgo , Procedimientos Endovasculares/métodos , Estudios Retrospectivos , Anciano , Embolización Terapéutica/métodos , Adulto , Arteria Cerebral Anterior/cirugía , Arteria Cerebral Anterior/diagnóstico por imagen , Stents , Resultado del TratamientoRESUMEN
(1) Background: Among Korean research papers there have been studies on the correlation between tuberculosis-hypertension and diabetes and the correlation between dementia-hypertension and diabetes, but there were no analysis data specifically on tuberculosis and dementia. (2) Methods: A total of 2992 tuberculosis patients in the Gyeongbuk region were analyzed through a final analysis of integrated disease and health management system data collected from 2021 to 2022. In this selection, patients with tuberculosis under 50 years of age and 368 people diagnosed with tuberculosis were excluded. (3) Results: From 2021 to 2022, among the 2992 tuberculosis patients in Gyeongsangbuk-do aged 50 or older, 2722 (91.0%) belonged to the general tuberculosis patient group, while 270 (9.0%) belonged to the dementia-tuberculosis patient group. The average age in the dementia-tuberculosis group was 81.4 years, significantly higher than the general group's average of 75.7 years. Within the dementia-tuberculosis patient group, 235 patients (87.0%) had underlying medical conditions in addition to dementia and tuberculosis. The tuberculosis treatment cure rate was 56.3% (1477 patients) in the general group and 38.9% (105 patients) in the dementia-tuberculosis patient group. (4) Conclusions: The cure rate was notably higher in the general group. Similarly, the mortality rate (deaths due to tuberculosis) was significantly higher in the dementia-tuberculosis patient group (7.0%, 19 patients) compared to the normal group (3.0%, 81 patients). The mortality rate in the dementia group was more than twice that of the general group.