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1.
J Infect Dis ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34794178

RESUMO

Little is known regarding COVID-19 vaccination rates in people with HIV (PWH), a vulnerable population with significant morbidity from COVID-19. We assessed COVID-19 vaccination rates among 6952 PWH in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) compared to region- and country-specific vaccination data. The global probability of COVID-19 vaccination through the end of July 2021 was 55% among REPRIEVE participants with rates varying substantially by Global Burden of Disease (GBD) super-region. Among PWH, factors associated with COVID-19 vaccination included residence in high-income regions, age, White race, male sex, BMI, and higher burden of cardiovascular risk.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34804394

RESUMO

Objective: To assess the prevalence of QTc prolongation in both non-diabetic and diabetic patients on TKIs. Some TKIs have been reported to cause QTc prolongation, which is prevalent in diabetes. However, there is no Risk Evaluation and Mitigation Strategy using series ECG to monitor those patients. Methods: Patients taking TKIs, with two ECGs recorded between 1 January 2010 and 31 December 2017 were selected from the electronic database. The QTc duration >450 ms was determined as prolonged. Percentage of QTc prolongation on participants were compared using Chi-Square test. Results: This study included 313 patients (age 66.1 ± 0.8 years and 57.5% are female) taking TKIs. In non-Diabetic patients, the prevalence of QTc prolongation is 19.1% (n = 253) before and 34.8% (n = 253) after treatment with TKIs (p < 0.001), respectively. In diabetic patients, the prevalence of QTc prolongation is 21.7% (n = 60) before and 40% (n = 60) after treatment with TKIs (p = 0.03), respectively. In addition, we examined the effect of modifying risk factors for cardiovascular disease (CVD) on the prevalence of QTc prolongation caused by TKIs. In non-diabetic patients, the prevalence of QTc prolongation is 33.3% (n = 57) before and 34.2% (n = 196) after risk factors modification (p = 0.91), respectively. In diabetic patients, the prevalence of QTc prolongation is 50% (n = 24) before and 33.3% (n = 36) after risk factors modification (p = 0.20), respectively. Conclusion: Use of TKIs is associated with a significantly increased risk of QTc prolongation for patients, particularly when patients are diabetic. Modification of risk factors for CVD does not significantly affect the prevalence of QTc prolongation caused by TKIs.

3.
Sci Rep ; 11(1): 19586, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599265

RESUMO

Deep learning convolutional neural network (CNN) can predict mortality from chest radiographs, yet, it is unknown whether radiologists can perform the same task. Here, we investigate whether radiologists can visually assess image gestalt (defined as deviation from an unremarkable chest radiograph associated with the likelihood of 6-year mortality) of a chest radiograph to predict 6-year mortality. The assessment was validated in an independent testing dataset and compared to the performance of a CNN developed for mortality prediction. Results are reported for the testing dataset only (n = 100; age 62.5 ± 5.2; male 55%, event rate 50%). The probability of 6-year mortality based on image gestalt had high accuracy (AUC: 0.68 (95% CI 0.58-0.78), similar to that of the CNN (AUC: 0.67 (95% CI 0.57-0.77); p = 0.90). Patients with high/very high image gestalt ratings were significantly more likely to die when compared to those rated as very low (p ≤ 0.04). Assignment to risk categories was not explained by patient characteristics or traditional risk factors and imaging findings (p ≥ 0.2). In conclusion, assessing image gestalt on chest radiographs by radiologists renders high prognostic accuracy for the probability of mortality, similar to that of a specifically trained CNN. Further studies are warranted to confirm this concept and to determine potential clinical benefits.

4.
Sci Rep ; 11(1): 20447, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34650074

RESUMO

Insufficient nutrition exchange and limited transportation of blood supply in a porous only scaffold often hinder bone formation, even though the porous scaffold is loaded with cells or growth factors. To overcome these issues, we developed a cell- and growth factor-free approach to induce bone formation in a critical-size bone defect by using an interconnected porous beta-tricalcium phosphate (ß-TCP) scaffold with multiple channels. In vitro cell experimental results showed that multiple channels significantly promoted cell attachment and proliferation of human bone marrow mesenchymal stem cells, stimulated their alkaline phosphatase activity, and up-regulated the osteogenic gene expression. Multiple channels also considerably stimulated the expression of various mechanosensing markers of the cells, such as focal adhesion kinase, filamentous actin, and Yes-associated protein-1 at both static and dynamic culturing conditions. The in vivo bone defect implantation results demonstrated more bone formation inside multiple-channeled scaffolds compared to non-channeled scaffolds. Multiple channels prominently accelerated collagen type I, bone sialoprotein and osteocalcin protein expression. Fluorochrome images and angiogenic marker CD31 staining exhibited more mineral deposition and longer vasculature structures in multiple-channeled scaffolds, compared to non-channeled scaffolds. All the findings suggested that the creation of interconnected multiple channels in the porous ß-TCP scaffold is a very promising approach to promote bone tissue regeneration.

5.
JACC Cardiovasc Interv ; 14(18): 1995-2005, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34556273

RESUMO

OBJECTIVES: The aim of this study was to compare 5-year cardiovascular, renal, and bioprosthetic valve durability outcomes in patients with severe aortic stenosis (AS) and chronic kidney disease (CKD) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). BACKGROUND: Patients with severe AS and CKD undergoing TAVR or SAVR are a challenging, understudied clinical subset. METHODS: Intermediate-risk patients with moderate to severe CKD (estimated glomerular filtration rate <60 mL/min/m2) from the PARTNER (Placement of Aortic Transcatheter Valve) 2A trial (patients randomly assigned to SAPIEN XT TAVR or SAVR) and SAPIEN 3 Intermediate Risk Registry were pooled. The composite primary outcome of death, stroke, rehospitalization, and new hemodialysis was evaluated using Cox regression analysis. Patients with and without perioperative acute kidney injury (AKI) were followed through 5 years. A core laboratory-adjudicated analysis of structural valve deterioration and bioprosthetic valve failure was also performed. RESULTS: The study population included 1,045 TAVR patients (512 SAPIEN XT, 533 SAPIEN 3) and 479 SAVR patients. At 5 years, SAVR was better than SAPIEN XT TAVR (52.8% vs 68.0%; P = 0.04) but similar to SAPIEN 3 TAVR (52.8% vs 58.7%; P = 0.89). Perioperative AKI was more common after SAVR than TAVR (26.3% vs 10.3%; P < 0.001) and was independently associated with long-term outcomes. Compared with SAVR, bioprosthetic valve failure and stage 2 or 3 structural valve deterioration were significantly greater for SAPIEN XT TAVR (P < 0.05) but not for SAPIEN 3 TAVR. CONCLUSIONS: In intermediate-risk patients with AS and CKD, SAPIEN 3 TAVR and SAVR were associated with a similar risk for the primary endpoint at 5 years. AKI was more common after SAVR than TAVR, and SAPIEN 3 valve durability was comparable with that of surgical bioprostheses.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência Renal Crônica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Humanos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
6.
Vaccine ; 39(41): 6095-6103, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34507857

RESUMO

BACKGROUND: Vaccine use during pregnancy affects maternal and infant health. Many women do not receive vaccines recommended during pregnancy; conversely, inadvertent exposure to vaccines contraindicated or not recommended during pregnancy may occur. We assessed exposure to two recommended vaccines and two vaccines not recommended during pregnancy among privately and Medicaid-insured women in the United States. METHODS: This study includes a retrospective cohort of pregnancies in women aged 12-55 years resulting in live birth, spontaneous abortion, or stillbirth identified in the IBM® MarketScan® Commercial, Blue Health Intelligence® (BHI®) Commercial, and IBM MarketScan Multi-State Medicaid Databases from August 1, 2016, to December 31, 2018. Gestational age at vaccination was determined using a validated algorithm. We examined vaccines (1) recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices (ACIP) (tetanus, diphtheria, and acellular pertussis [Tdap]; inactivated influenza) and (2) not recommended (human papillomavirus [HPV]) or contraindicated (measles, mumps, and rubella [MMR]). RESULTS: We identified 496,771 (MarketScan Commercial), 858,961 (BHI), and 289,573 (MarketScan Medicaid) pregnancies (approximately 75% aged 20-34 years). Across these three databases, 52.1%, 50.3%, and 31.3% of pregnancies, respectively, received Tdap, most often at a gestational age of 28 weeks, and influenza vaccination occurred in 32.1%, 30.8%, and 18.0% of pregnancies, respectively. HPV vaccination occurred in < 0.2% of pregnancies, mostly in the first trimester among women aged 12-19 years, and MMR was administered in < 0.1% of pregnancies. Use of other contraindicated vaccines per ACIP (e.g., varicella, live attenuated influenza) was rare. CONCLUSION: Maternal vaccination with ACIP-recommended vaccines was suboptimal among privately and Medicaid-insured patients, with lower vaccination coverage among Medicaid-insured pregnancies than their privately insured counterparts. Inadvertent exposure to contraindicated vaccines during pregnancy was rare. This study evaluated only vaccinations reimbursed among insured populations and may have limited generalizability to uninsured populations.


Assuntos
Vacinas contra Difteria, Tétano e Coqueluche Acelular , Vacinas contra Influenza , Adolescente , Adulto , Criança , Feminino , Humanos , Vacinas contra Influenza/efeitos adversos , Medicaid , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Estados Unidos , Vacinação , Cobertura Vacinal , Adulto Jovem
7.
Artigo em Inglês | MEDLINE | ID: mdl-34535393

RESUMO

BACKGROUND AND OBJECTIVE: Studies have reported an increased tuberculosis (TB) incidence among patients with end-stage renal disease (ESRD). This nationwide nested Case-control study investigated the risk of active TB due to nosocomial exposure and its correlation with the delay in TB treatment in hemodialysis patients. METHODS: Adult (aged ≥20 years) patients with incident ESRD over 2000-2010 were identified from Taiwan National Health Insurance Research Database; 2331 patients with incident active TB (Case) were matched with 11,655 patients without TB (control) by age, sex, year of ESRD onset, Charlson comorbidity index, chronic obstructive pulmonary disease, and diabetes mellitus, at a 1:5 case-to-control ratio. RESULTS: Compared with the control group, the Case group had greater nosocomial exposure to index patients with pulmonary TB (2.36 vs. 0.11 month of exposure, p < 0.001). Nosocomial exposure increased active TB risk (adjusted odds ratio [OR; 95% confidence interval, CI]: 1.60 [1.55-1.66] per month of exposure), particularly when the exposure time was either within 6 months before the index case was diagnosed or 6-15 months before the ESRD patient became an incident active TB case. For patients with active TB, cough-related medication prescriptions (proxy for cough symptoms) exponentially increased over 6 months before TB treatment. CONCLUSION: Nosocomial exposure attributed to delay in the diagnosis of index pulmonary TB is important in TB transmission among patients undergoing regular hemodialysis. Additional studies investigating how TB can be diagnosed and treated early are warranted. SUMMARY AT A GLANCE: Our study revealed that nosocomial exposure, attributed to delay in pulmonary TB diagnosis, is important in TB transmission among patients undergoing regular hemodialysis. Strategies to diagnose and treat TB early are crucial to infection control, and they warrant further investigations.

8.
Cell Mol Neurobiol ; 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34347195

RESUMO

Neurons are susceptible to different cellular stresses and this vulnerability has been implicated in the pathogenesis of Huntington's disease (HD). Accumulating evidence suggest that acute or chronic stress, depending on its duration and severity, can cause irreversible cellular damages to HD neurons, which contributes to neurodegeneration. In contrast, how normal and HD neurons respond during the resolution of a cellular stress remain less explored. In this study, we challenged normal and HD cells with a low-level acute ER stress and examined the molecular and cellular responses after stress removal. Using both striatal cell lines and primary neurons, we first showed the temporal activation of p-eIF2α-ATF4-GADD34 pathway in response to the acute ER stress and during recovery between normal and HD cells. HD cells were more vulnerable to cell death during stress recovery and were associated with increased number of apoptotic/necrotic cells and decreased cell proliferation. This is also supported by the Gene Ontology analysis from the RNA-seq data which indicated that "apoptosis-related Biological Processes" were more enriched in HD cells during stress recovery. We further showed that HD cells were defective in restoring global protein synthesis during stress recovery and promoting protein synthesis by an integrated stress response inhibitor, ISRIB, could attenuate cell death in HD cells. Together, these data suggest that normal and HD cells undergo distinct mechanisms of transcriptional reprogramming, leading to different cell fate decisions during the stress recovery.

9.
EBioMedicine ; 70: 103517, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34364166
10.
Vaccine ; 39(38): 5368-5375, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34384636

RESUMO

BACKGROUND: Anaphylaxis is a rare, serious allergic reaction. Its identification in large healthcare databases can help better characterize this risk. OBJECTIVE: To create an ICD-10 anaphylaxis algorithm, estimate its positive predictive values (PPVs) in a post-vaccination risk window, and estimate vaccination-attributable anaphylaxis rates in the Medicare Fee For Service (FFS) population. METHODS: An anaphylaxis algorithm with core and extended portions was constructed analyzing ICD-10 anaphylaxis claims data in Medicare FFS from 2015 to 2017. Cases of post-vaccination anaphylaxis among Medicare FFS beneficiaries were then identified from October 1, 2015 to February 28, 2019 utilizing vaccine relevant anaphylaxis ICD-10 codes. Information from medical records was used to determine true anaphylaxis cases based on the Brighton Collaboration's anaphylaxis case definition. PPVs were estimated for incident anaphylaxis and the subset of vaccine-attributable anaphylaxis within a 2-day post-vaccination risk window. Vaccine-attributable anaphylaxis rates in Medicare FFS were also estimated. RESULTS: The study recorded 66,572,128 vaccinations among 21,685,119 unique Medicare FFS beneficiaries. The algorithm identified a total of 190 suspected anaphylaxis cases within the 2-day post-vaccination window; of these 117 (62%) satisfied the core algorithm, and 73 (38%) additional cases satisfied the extended algorithm. The core algorithm's PPV was 66% (95% CI [56%, 76%]) for identifying incident anaphylaxis and 44% (95% CI [34%, 56%]) for vaccine-attributable anaphylaxis. The vaccine-attributable anaphylaxis incidence rate after any vaccination was 0.88 per million doses (95% CI [0.67, 1.16]). CONCLUSION: The ICD-10 claims algorithm for anaphylaxis allows the assessment of anaphylaxis risk in real-world data. The algorithm revealed vaccine-attributable anaphylaxis is rare among vaccinated Medicare FFS beneficiaries.


Assuntos
Anafilaxia , Vacinas , Idoso , Algoritmos , Anafilaxia/induzido quimicamente , Anafilaxia/epidemiologia , Humanos , Incidência , Classificação Internacional de Doenças , Medicare , Estados Unidos/epidemiologia , Vacinas/efeitos adversos
11.
Matern Child Health J ; 25(10): 1508-1515, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34398407

RESUMO

PURPOSE: Protecting and advancing maternal and child health is a critical goal to both society and to the economy, given that their health is a predictor of the next generation's health. Yet despite this recognition, many of the communities aiming to improve maternal and child health still problem-solve in silos: age silos, disease silos, organizational silos, disciplinary silos, data silos, and communication silos, often created or exacerbated by the disconnected approaches to research, funding, and reporting. These silos limit discovery and spread of new solutions to important maternal and child health problems. DESCRIPTION: In this paper, we will discuss federal incentive prizes as a tool to break down silos and to engineer cognitive diversity and transdisciplinary collaboration. ASSESSMENT: In 2018, the United States Health Resources and Services Administration, Maternal and Child Health Bureau (HRSA MCHB) launched the "Maternal and Child Health Bureau Grand Challenges," a suite of four prize competitions totaling $1.5 million addressing critical issues in maternal and child health. These included federal challenges designed to (1) prevent childhood obesity in low-income communities, (2) improve the remote monitoring of pregnancy, (3) improve care coordination and planning for children with special health care needs, and (4) prevent opioid misuse among pregnant women and new mothers. CONCLUSION: The ability to incentivize innovation to address critical public health issues cannot rest in the private sector alone. Complementing other investments, the Challenge mechanism's power to catalyze the rapid development of innovative solutions can improve how we address barriers to achieve optimal maternal and child health for the families that we serve.


Assuntos
Distinções e Prêmios , Serviços de Saúde da Criança , Serviços de Saúde Materna , Obesidade Pediátrica , Criança , Saúde da Criança , Pré-Escolar , Feminino , Humanos , Motivação , Gravidez , Estados Unidos
12.
BMC Med Genomics ; 14(1): 176, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215255

RESUMO

BACKGROUND: Huntingtin (Htt) protein is the product of the gene mutated in Huntington's disease (HD), a fatal, autosomal dominant, neurodegenerative disorder. Normal Htt is essential for early embryogenesis and the development of the central nervous system. However, the role of Htt in adult tissues is less defined. Following the recent promising clinical trial in which both normal and mutant Htt mRNA were knocked down in HD patients, there is an urgent need to fully understand the molecular consequences of knocking out/down Htt in adult tissues. Htt has been identified as an important transcriptional regulator. Unbiased investigations of transcriptome changes with RNA-sequencing (RNA-Seq) have been done in multiple cell types in HD, further confirming that transcriptional dysregulation is a central pathogenic mechanism in HD. However, there is lack of direct understanding of the transcriptional regulation by normal Htt. METHODS: To investigate the transcriptional role of normal Htt, we first knocked out Htt in the human neuroblastoma SH-SY5Y cell line using the CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9 (CRISPR-associated protein 9) gene editing approach. We then performed RNA-seq analysis on Htt-null and wild type SH-SY5Y cells to probe the global transcriptome changes induced by Htt deletion. RESULTS: In general, Htt has a widespread effect on gene transcription. Functional analysis of the differentially expressed genes (DEGs) using various bioinformatic tools revealed irregularities in pathways related to cell communication and signaling, and more specifically those related to neuron development, neurotransmission and synaptic signaling. We further examined the transcription factors that may regulate these DEGs. Consistent with the disrupted pathways associated with cellular development, we showed that Htt-null cells exhibited slower cell proliferation than wild type cells. We finally validated some of the top DEGS with quantitative RT-PCR. CONCLUSIONS: The widespread transcriptome changes in Htt-null cells could be directly caused by the loss of Htt-mediated transcriptional regulation or due to the secondary consequences of disruption in the gene regulatory network. Our study therefore provides valuable information about key genes associated with Htt-mediated transcription and improves our understanding of the molecular mechanisms underlying the cellular functions of normal and mutant Htt.

13.
JACC Cardiovasc Interv ; 14(14): 1565-1574, 2021 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-34294398

RESUMO

OBJECTIVES: The aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR). BACKGROUND: There is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR. METHODS: In the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter. RESULTS: Among 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality. CONCLUSIONS: In the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.


Assuntos
Estenose da Valva Aórtica , Fibrilação Atrial , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Assistência ao Convalescente , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/epidemiologia , Estenose da Valva Aórtica/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Alta do Paciente , Fatores de Risco , Índice de Gravidade de Doença , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
14.
Radiol Cardiothorac Imaging ; 3(3): e210016, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34235445

RESUMO

Purpose: To perform a retrospective review of Coronary Artery Disease Reporting and Data System (CAD-RADS) adoption at a high-volume cardiac CT service. Materials and Methods: In this retrospective study, the adoption of CAD-RADS in 6562 coronary CT angiography (CTA) reports from January 1, 2017, to February 13, 2020, was evaluated. Reports without CAD-RADS were classified as opt-outs or exceptions to CAD-RADS. CAD-RADS classifications were retrospectively assigned to the opt-outs and the clinical indications for coronary CTA. Results: CAD-RADS scores were reported in 95% (6264 of 6562) of cases. Among the 5% (n = 298) of reports not reported according to CAD-RADS, 58% (n = 172) were considered opt-outs and 42% (n = 126) were exceptions. Cases with higher degree of stenosis, stents, and coronary artery bypass grafts (CABGs) occurred more often in opt-outs versus reports with CAD-RADS (odds ratio [OR], 8.3 [95% CI: 1.6, 42.1]; P < .001). The quarterly opt-out rate decreased over consecutive quarters in the 1st year (OR, 0.77 [95% CI: 0.61, 0.96]; P = .01), then stabilized. Quarterly opt-out rate for patients with stents decreased over time (OR, 0.82 [95% CI: 0.73, 0.92]; P = .008), as did the opt-out rates in patients with CABG (OR, 0.83 [95% CI: 0.76, 0.91]; P < .001). Exceptions (n = 126) included coronary dissections (44%), anomalous coronary arteries (41%), coronary artery aneurysms or pseudoaneurysms (10%), vasculitis (2%), stent complications (2%), and extrinsic compression of grafts (2%). Conclusion: CAD-RADS was adopted rapidly and widely. Readers opted out of its use most often in complex cases of CAD, and the most common exceptions were coronary dissections and anomalous coronary artery.Keywords: Coronary Arteries, CT Angiography© RSNA, 2021.

15.
JAMA Netw Open ; 4(6): e2114923, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34185068

RESUMO

Importance: Cardiovascular disease (CVD) is increased among people with HIV (PWH), but little is known regarding the prevalence and extent of coronary artery disease (CAD) and associated biological factors in PWH with low to moderate traditional CVD risk. Objectives: To determine unique factors associated with CVD in PWH and to assess CAD by coronary computed tomography angiography (CTA) and critical pathways of arterial inflammation and immune activation. Design, Setting, and Participants: This cohort study among male and female PWH, aged 40 to 75 years, without known CVD, receiving stable antiretroviral therapy, and with low to moderate atherosclerotic cardiovascular disease (ASCVD) risk according to the 2013 American College of Cardiology/American Heart Association pooled cohort equation, was part of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), a large, ongoing primary prevention trial of statin therapy among PWH conducted at 31 US sites. Participants were enrolled from May 2015 to February 2018. Data analysis was conducted from May to December 2020. Exposure: HIV disease. Main Outcomes and Measures: The primary outcome was the prevalence and composition of CAD assessed by coronary CTA and, secondarily, the association of CAD with traditional risk indices and circulating biomarkers, including insulin, monocyte chemoattractant protein 1 (MCP-1), interleukin (IL) 6, soluble CD14 (sCD14), sCD163, lipoprotein-associated phospholipase A2 (LpPLA2), oxidized low-density lipoprotein (oxLDL), and high-sensitivity C-reactive protein (hsCRP). Results: The sample included 755 participants, with a mean (SD) age of 51 (6) years, 124 (16%) female participants, 267 (35%) Black or African American participants, 182 (24%) Latinx participants, a low median (interquartile range) ASCVD risk (4.5% [2.6%-6.8%]), and well-controlled viremia. Overall, plaque was seen in 368 participants (49%), including among 52 of 175 participants (30%) with atherosclerotic CVD (ASCVD) risk of less than 2.5%. Luminal obstruction of at least 50% was rare (25 [3%]), but vulnerable plaque and high Leaman score (ie, >5) were more frequently observed (172 of 755 [23%] and 118 of 743 [16%], respectively). Overall, 251 of 718 participants (35%) demonstrated coronary artery calcium score scores greater than 0. IL-6, LpPLA2, oxLDL, and MCP-1 levels were higher in those with plaque compared with those without (eg, median [IQR] IL-6 level, 1.71 [1.05-3.04] pg/mL vs 1.45 [0.96-2.60] pg/mL; P = .008). LpPLA2 and IL-6 levels were associated with plaque in adjusted modeling, independent of traditional risk indices and HIV parameters (eg, IL-6: adjusted odds ratio, 1.07; 95% CI, 1.02-1.12; P = .01). Conclusions and Relevance: In this study of a large primary prevention cohort of individuals with well-controlled HIV and low to moderate ASCVD risk, CAD, including noncalcified, nonobstructive, and vulnerable plaque, was highly prevalent. Participants with plaque demonstrated higher levels of immune activation and arterial inflammation, independent of traditional ASCVD risk and HIV parameters.

17.
J Tissue Eng ; 12: 20417314211021220, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34188794

RESUMO

The nucleus pulposus (NP) of the intervertebral disc plays a critical role in distributing mechanical loads to the axial skeleton. Alterations in NP cells and, consequently, NP matrix are some of the earliest changes in the development of disc degeneration. Previous studies demonstrated a role for laminin-presenting biomaterials in promoting a healthy phenotype for human NP cells from degenerated tissue. Here we investigate the use of laminin-mimetic peptides presented individually or in combination on a poly(ethylene) glycol hydrogel as a platform to modulate the behaviors of degenerative human NP cells. Data confirm that NP cells attach to select laminin-mimetic peptides that results in cell signaling downstream of integrin and syndecan binding. Furthermore, the peptide-functionalized hydrogels demonstrate an ability to promote cell behaviors that mimic that of full-length laminins. These results identify a set of peptides that can be used to regulate NP cell behaviors toward a regenerative engineering strategy.

18.
Cells ; 10(5)2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946915

RESUMO

Many decellularized extracellular matrix-derived whole organs have been widely used in studies of tissue engineering and cancer models. However, decellularizing porcine esophagus to obtain decellularized esophageal matrix (DEM) for potential biomedical applications has not been widely investigated. In this study a modified decellularization protocol was employed to prepare a porcine esophageal DEM for the study of cancer cell growth. The cellular removal and retention of matrix components in the porcine DEM were fully characterized. The microstructure of the DEM was observed using scanning electronic microscopy. Human esophageal squamous cell carcinoma (ESCC) and human primary esophageal fibroblast cells (FBCs) were seeded in the DEM to observe their growth. Results show that the decellularization process did not cause significant loss of mechanical properties and that blood ducts and lymphatic vessels in the submucosa layer were also preserved. ESCC and FBCs grew on the DEM well and the matrix did not show any toxicity to cells. When FBS and ESCC were cocultured on the matrix, they secreted more periostin, a protein that supports cell adhesion on matrix. This study shows that the modified decellularization protocol can effectively remove the cell materials and maintain the microstructure of the porcine esophageal matrix, which has the potential application of studying cell growth and migration for esophageal cancer models.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Esôfago/citologia , Matriz Extracelular/química , Tecidos Suporte/química , Animais , Carcinoma de Células Escamosas/patologia , Adesão Celular , Linhagem Celular Tumoral , Células Cultivadas , Técnicas de Cocultura/métodos , Módulo de Elasticidade , Neoplasias Esofágicas/patologia , Esôfago/metabolismo , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Camundongos , Suínos
19.
Nature ; 592(7855): 629-633, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33828294

RESUMO

There is a growing focus on making clinical trials more inclusive but the design of trial eligibility criteria remains challenging1-3. Here we systematically evaluate the effect of different eligibility criteria on cancer trial populations and outcomes with real-world data using the computational framework of Trial Pathfinder. We apply Trial Pathfinder to emulate completed trials of advanced non-small-cell lung cancer using data from a nationwide database of electronic health records comprising 61,094 patients with advanced non-small-cell lung cancer. Our analyses reveal that many common criteria, including exclusions based on several laboratory values, had a minimal effect on the trial hazard ratios. When we used a data-driven approach to broaden restrictive criteria, the pool of eligible patients more than doubled on average and the hazard ratio of the overall survival decreased by an average of 0.05. This suggests that many patients who were not eligible under the original trial criteria could potentially benefit from the treatments. We further support our findings through analyses of other types of cancer and patient-safety data from diverse clinical trials. Our data-driven methodology for evaluating eligibility criteria can facilitate the design of more-inclusive trials while maintaining safeguards for patient safety.

20.
JACC Cardiovasc Imaging ; 14(11): 2186-2195, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33865792

RESUMO

OBJECTIVES: The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD. BACKGROUND: Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed. METHODS: In PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD. RESULTS: Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007). CONCLUSIONS: Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.

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