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1.
J Alzheimers Dis ; 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33579854

RESUMO

BACKGROUND: Mechanisms through which arterial stiffness impacts cognitive function are crucial for devising better strategies to prevent cognitive decline. OBJECTIVE: To examine the associations of arterial stiffness with white matter integrity and cognition in community dwellings, and to investigate whether white matter injury was the intermediate of the associations between arterial stiffness and cognition. METHODS: This study was a cross-sectional analysis on 952 subjects (aged 55.5±9.1 years) who underwent diffusion tensor imaging and measurement of brachial-ankle pulse wave velocity (baPWV). Both linear regression and tract-based spatial statistics were used to investigate the association between baPWV and white matter integrity. The association between baPWV and global cognitive function, measured as the mini-mental state examination (MMSE) was evaluated. Mediation analysis was performed to assess the influence of white matter integrity on the association of baPWV with MMSE. RESULTS: Increased baPWV was significantly associated with lower mean global fractional anisotropy (ß= -0.118, p <  0.001), higher mean diffusivity (ß= 0.161, p <  0.001), axial diffusivity (ß= 0.160, p <  0.001), and radial diffusivity (ß= 0.147, p <  0.001) after adjustment of age, sex, and hypertension, which were measures having a direct effect on arterial stiffness and white matter integrity. After adjustment of age, sex, education, apolipoprotein E ɛ4, cardiovascular risk factors, and brain atrophy, we found an association of increased baPWV with worse performance on MMSE (ß= -0.093, p = 0.011). White matter disruption partially mediated the effect of baPWV on MMSE. CONCLUSION: Arterial stiffness is associated with white matter disruption and cognitive decline. Reduced white matter integrity partially explained the effect of arterial stiffness on cognition.

2.
Int J Cardiol ; 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33529668

RESUMO

BACKGROUND: Right ventricular apex (RVA) is still the most common implanted site in the world. There are a large number of RVA pacing population who have been carrying dual-chamber permanent pacemaker (PPM) over decades. Comparison of left ventricular dyssynchrony, morphology and systolic function between RVA pacing population and healthy population is unknown. METHOD: This case-control study enrolled 61 patients suffered from complete atrioventricular block (III°AVB) for replacement of dual-chamber PPM. Then, 61 healthy controls matched with PPM patients in gender, age, follow-up duration and complications were included. The lead impedance, pacing threshold and sensing were compared between at implantation and long-term follow-up. Left ventricular (LV) dyssynchrony, morphology and systolic function were compared between RVA pacing population (RVA group) and healthy population (healthy group) at implantation (baseline) and follow-up. And clarify the predictors of LV systolic function in RVA group at follow-up. RESULTS: After 112.44 ± 34.94 months of follow-up, comparing with parameters at implantation, atrial lead impedance decreased significantly (690 ± 2397 Ω vs 613 ± 2257 Ω, p = 0.048); atrial pacing threshold has a increased trend and P-wave amplitude has a decreased trend, but there was no statistical differences; while, RVA ventricular lead threshold increased significantly (0.50 ± 0.23 V vs 0.91 ± 0.47 V, p < 0.001), impedance (902 ± 397 Ω vs 680 ± 257 Ω,p < 0.001) and R-wave amplitude (11.71 ± 9.40mv vs 7.00 ± 6.91 mv, p < 0.001) decreased significantly. Compared with healthy group, long-term RVA pacing significantly increased ventricular dyssynchrony (mean QRS duration, 156.21 ± 29.80 ms vs 97.08 ± 15.70 ms, p < 0.001), left atrium diameter (LAD, 40.61 ± 6.15 mm vs 37.49 ± 4.80 mm,p = 0.002), left ventricular end-diastolic diameter (LVEDD, 49.15 ± 5.93 mm vs 46.41 ± 3.80 mm,p = 0.003), left ventricular hypertrophy (LVMI, 121.86 ± 41.52 g/m2 vs 98.41 ± 25.29 g/m2,p < 0.001), significantly deteriorated degree of tricuspid regurgitation (p < 0.001), and significantly decreased left ventricular ejection fraction (LVEF, 61.38 ± 8.10% vs 64.64 ± 5.85%, p = 0.012), but after long-term RVA pacing, the mean LVEF was still more than 50%. Long-term RVA group LVEF was negatively correlated with preimplantation LVMI (B = -0.055,t = -2.244,p = 0.029), LVMI at follow-up (B = -0.081,t = -3.864,p = 0.000) and tricuspid regurgitation at follow-up (B = -3.797,t = -3.599,p = 0.001). CONCLUSION: In conclusion, although long-term RVA pacing has significantly effects on left ventricular dyssynchrony, morphology and systolic function in III°AVB patients, the mean LVEF is still >50%. High preimplantation LVMI can predict the decline of LVEF.

3.
EJNMMI Phys ; 8(1): 3, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411102

RESUMO

BACKGROUND: 99mTc-PYP scintigraphy provides differential diagnosis of ATTR cardiomyopathy (ATTR-CM) from light chain cardiac amyloidosis and other myocardial disorders without biopsy. This study was aimed to assess the diagnostic feasibility and the operator reproducibility of 99mTc-PYP quantitative SPECT. METHOD: Thirty-seven consecutive patients who underwent a 99mTc-PYP thorax planar scan followed by SPECT and CT scans to diagnose suspected ATTR-CM were enrolled. For the quantitative SPECT, phantom studies were initially performed to determine the image conversion factor (ICF) and partial volume correction (PVC) factor to recover 99mTc-PYP activity concentration in the myocardium for calculating the standardized uptake value (SUV) (unit: g/ml). SUVmax was compared among groups of ATTR-CM, AL cardiac amyloidosis, and other pathogens (others) and among categories of Perugini visual scores (grades 0-3). The intra- and inter-operator reproducibility of quantitative SPECT was verified, and the corresponded repeatability coefficient (RPC) was calculated. RESULTS: The ICF was 79,327 Bq/ml to convert count rate in pixel to 99mTc activity concentration. PVC factor as a function of the measured activity concentration ratio in the myocardium and blood-pool was [y = 1.424 × (1 - exp(- 0.759 × x)) + 0.104]. SUVmax of ATTR-CM (7.50 ± 2.68) was significantly higher than those of AL (1.96 ± 0.35) and others (2.00 ± 0.74) (all p < 0.05). SUVmax of grade 3 (8.95 ± 1.89) and grade 2 (4.71 ± 0.23) were also significantly higher than those of grade 1 (1.92 ± 0.31) and grade 0 (1.59 ± 0.39) (all p < 0.05). Correlation coefficient (R2) of SUVmax reached 0.966 to 0.978 with only small systematic difference (intra = - 0.14; inter = - 0.23) between two repeated measurements. Intra- and inter-operator RPCs were 0.688 and 0.877. CONCLUSIONS: 99mTc-PYP quantitative SPECT integrated with adjustable PVC factors is feasible to quantitatively and objectively assess the burden of cardiac amyloidosis for diagnosis of ATTR-CM.

4.
Sci China Life Sci ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33439457

RESUMO

We aimed to assess the associations of large artery stenosis (LAS) and cerebral small vessel disease (CSVD) with the risk of ischemic stroke and to investigate their respective and combined contributions. In the prospective population-based Shunyi Study, 1,082 stroke-free participants aged 55.9±9.1 years were included. Participants were followed for incident stroke throughout the study period (2013-2019). Total small vessel disease score was used to measure CSVD burden. Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound. We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models. During a mean follow-up of 4.2 years, 34 participants (3.1%) experienced at least one ischemic stroke. Severe LAS (≥50% stenosis versus no stenosis: HR=3.27 (95% CI: 1.31-8.18)) and high CSVD burden (total small vessel disease score 2-4 versus 0 point: HR=12.73 (4.83-33.53)) were associated with increased stroke risk independently. In multivariate models, CSVD burden (7.72%) explained a larger portion of the variation in stroke risk than severity of LAS (3.49%). Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects, while those with high CSVD burden deserve more attention in primary prevention of stroke.

5.
Heart Fail Rev ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443725

RESUMO

Noninvasive positive-pressure ventilation (NPPV) is recognized as an effective adjuvant therapy for sleep-disordered breathing (SDB) in heart failure patients with reduced ejection fraction (HFrEF + SDB). In recent years, some studies have found that adaptive servo-ventilation (ASV) has a negative impact on survival, especially among patients with central sleep apnea (CSA), the use of which is controversial. This study aims to explore the effects of NPPV on cardiac function and survival in patients with sleep-disordered breathing and chronic congestive heart failure. This meta-analysis was based on literature searches of publications published before August 31, 2019, in the PubMed, EMBASE, Cochrane Library, and Web of Science databases. A total of 88 independent studies were summarized and compared, comprising a sampling of 19,259 subjects. Compared with the nontreatment group, treatment with ASV had no effect on all-cause mortality in patients with HFrEF + CSA (hazard ratio (HR) = 1.13 [0.84, 1.51]). Short-term treatment with ASV, e.g., 3-6 months, was significantly beneficial regarding event-free survival in patients with HFrEF + CSA (HR = 0.13 [0.04, 0.45]). Periodic short-term (e.g., 3-6 months) positive-pressure ventilation can significantly improve cardiac function, which is beneficial for the survival of patients with HFrEF + CSA. Attention should be paid to the length and period of treatment, as prolonged treatment may have negative effects.

6.
Am J Hum Genet ; 108(2): 337-345, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33434492

RESUMO

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.


Assuntos
Transtornos 46, XX do Desenvolvimento Sexual/genética , Anormalidades Congênitas/genética , Ductos Paramesonéfricos/anormalidades , Ductos Paramesonéfricos/crescimento & desenvolvimento , Mutação , Ductos Mesonéfricos/crescimento & desenvolvimento , Adulto , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 7/genética , Códon sem Sentido , Feminino , Estudos de Associação Genética , Pleiotropia Genética , Proteínas Homeobox A10/genética , Proteínas de Homeodomínio/genética , Humanos , Fator de Transcrição PAX8/genética , Herança Paterna , Penetrância , Proteínas com Domínio T/genética , Fatores de Transcrição/genética , Proteínas Wnt/genética , Ductos Mesonéfricos/anormalidades
7.
J Cosmet Dermatol ; 20(2): 372-380, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33350028

RESUMO

BACKGROUND: The emergence of COVID-19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS-CoV-2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS-CoV-2 can be found in the pressure injury exudates in patients with severe COVID-19 infections. METHODS: 46 critically ill COVID-19 patients who were admitted to the ICU of the Sino-French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT-PCRs were conducted to detect SARS-CoV-2 viral RNA. RESULTS: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS-CoV-2 by RT-PCR. CONCLUSION: Our study suggests that it is rather unlikely that COVID-19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries.


Assuntos
/virologia , Exsudatos e Transudatos/virologia , Lesão por Pressão/virologia , /isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
8.
Sci Adv ; 6(50)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33298433

RESUMO

DNA methylation plays critical roles in vascular pathology of pulmonary hypertension (PH). The underlying mechanism, however, remains undetermined. Here, we demonstrate that global DNA methylation was elevated in the lungs of PH rat models after monocrotaline administration or hypobaric hypoxia exposure. We showed that DNA methyltransferase 3B (DNMT3B) was up-regulated in both PH patients and rodent models. Furthermore, Dnmt3b -/- rats exhibited more severe pulmonary vascular remodeling. Consistently, inhibition of DNMT3B promoted proliferation/migration of pulmonary artery smooth muscle cells (PASMCs) in response to platelet-derived growth factor-BB (PDGF-BB). In contrast, overexpressing DNMT3B in PASMCs attenuated PDGF-BB-induced proliferation/migration and ameliorated hypoxia-mediated PH and right ventricular hypertrophy in mice. We also showed that DNMT3B transcriptionally regulated inflammatory pathways. Our results reveal that DNMT3B is a previously undefined mediator in the pathogenesis of PH, which couples epigenetic regulations with vascular remodeling and represents a therapeutic target to tackle PH.

9.
Aging Dis ; 11(6): 1623-1639, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33269111

RESUMO

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular disease characterized by pulmonary vasculature reconstruction and right ventricular dysfunction. The mortality rate of PAH remains high, although multiple therapeutic strategies have been implemented in clinical practice. These drugs mainly target the endothelin-1, prostacyclin and nitric oxide pathways. Management for PAH treatment includes improving symptoms, enhancing quality of life, and extending survival rate. Existing drugs developed to treat the disease have resulted in enormous economic and healthcare liabilities. The estimated cost for advanced PAH has exceeded $200,000 per year. The pathogenesis of PAH is associated with numerous molecular processes. It mainly includes germline mutation, inflammation, dysfunction of pulmonary arterial endothelial cells, epigenetic modifications, DNA damage, metabolic dysfunction, sex hormone imbalance, and oxidative stress, among others. Findings based on the pathobiology of PAH may have promising therapeutic outcomes. Hence, faced with the challenges of increasing healthcare demands, in this review, we attempted to explore the pathological mechanisms and alternative therapeutic targets, including other auxiliary devices or interventional therapies, in PAH. The article will discuss the potential therapies of PAH in detail, which may require further investigation before implementation.

10.
Eur J Neurol ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33377242

RESUMO

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinical imaging syndrome with diverse etiology. Total homocysteine (HCY) level might increase the risk of myocardial and cerebral infarction by damaging the vascular endothelium. We aimed to explore the correlation between total HCY and CSVD imaging burden, based on Mendelian randomization methods. METHODS: A total of 1,023 participants of the Shunyi study, a population-based cohort study, were included. Vascular risk factors, total HCY levels and methylenetetrahydrofolate reductase (MTHFR) gene mutations (C677T and A1298C) were examined. CSVD imaging markers, including lacunes, cerebral microbleeds, white matter hyperintensity, enlarged perivascular space and brain parenchymal fraction (BPF) were also assessed. RESULTS: Mutations of C677T were significantly correlated with increased total HCY levels (CC→TT: ß = 0.28, p < 0.0001), while mutations of A1298C were correlated with decreased total HCY levels (AA→AC: ß = -0.13, p < 0.0001; AA→CC: ß = -0.25, p = 0.004). In the Mendelian randomization study, the C677T genotype was significantly associated with lacunes (CC→CT: odds ratio [OR] 2.76, p = 0.008; CC→TT: OR 2.50, p = 0.018), and the A1298C genotype was significantly correlated with BPF (AA→CC: ß = 1.32, p = 0.015). Similarly, in multivariate regression analysis, total HCY levels were significantly correlated with lacunes (OR 2.14, p < 0.0001) and negatively correlated with BPF (ß = -0.55, p = 0.004). Age, sex and vascular risk factors were adjusted for. CONCLUSIONS: Total HCY level was correlated with imaging burden of CSVD, especially with lacunes and brain volume loss. For individuals with risk genetic predisposition, enhanced homocysteine-lowering strategies might be necessary to reduce the risk and progress of CSVD.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33369674

RESUMO

OBJECTIVE: Myocardial involvement (MCI) is known to increase morbidity and mortality in polymyositis (PM) and dermatomyositis (DM). This study aims to investigate whether complicating with ventricular arrhythmia (VA) predicts poor outcomes in patients with PM/DM-related myocardial involvement (PM/DM-MCI). METHODS: We reviewed all PM/DM-MCI patients admitted in Peking Union Medical College Hospital from October 1997 to April 2019. VA and the other possible risk factors for the composite end point, including death from any cause and rehospitalization for cardiac causes, were analysed. RESULTS: A total of 75 PM/DM-MCI patients (44 PM and 31 DM) were enrolled, of which 27 (36%) met the composite end point during a median follow-up of 24 months. Independent prognostic factors for the composite end point includes VA (HR 4.215, 95% CI [1.737, 10.230]), NT-proBNP > 3415 pg/ml (HR 2.606, 95% CI [1.203, 5.646]), interstitial lung disease (HR 2.688, 95% CI [1.209, 5.978]), and anti-cardiac remodelling therapy (HR 0.302, 95% CI [0.115, 0.792]). The 3-year event-free survival rate of patients without VA was significantly higher than that of patients with VA (63.3% vs 40.7%, p = 0.034). Skin lesions (OR 0.163, 95% CI [0.051, 0.523]) and positive antimitochondrial antibody (OR 3.484, 95% CI [1.192, 10.183]) were independent predictors of VA. CONCLUSION: VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.

12.
Can J Cardiol ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33310144

RESUMO

BACKGROUND: Coronary artery involvement is a severe but uncommon manifestation of polyarteritis nodosa (PAN), so clinicians have little knowledge of it. Our aim is to investigate the clinical characteristics, risk factors and outcomes of patients with PAN complicated with coronary artery lesions. METHODS: Data from 145 patients with PAN who were admitted to Peking Union Medical College Hospital from January 2000 to September 2019 were retrospectively collected. RESULTS: Nineteen (13.1%) patients had coronary artery lesions due to PAN. The age at the onset of PAN was 32.3±11.8 years. The two groups exhibited no significant differences in common risk factors for coronary arterial atherosclerosis. Affected branches of the coronary arteries were the left anterior descending branch (LAD) (15 patients), right coronary artery (RCA) (14 patients) and left circumflex branch (LCX) (9 patients). Eleven of these nineteen patients exhibited multivessel lesions. Multivariate logistic regression analysis showed that celiac artery involvement (OR 3.722, 95% CI 1.115-12.427, p=0.033) and new-onset hypertension (OR 6.668, 95% CI 1.936-22.961, p=0.003) were risk factors for coronary artery involvement in PAN patients. Stent placement was performed for 2 patients, and in-stent restenosis occurred in one patient a year later. CONCLUSIONS: PAN with coronary artery involvement exhibits more combined involvement of arteries of other organs and more severe diseases. PAN should be considered when treating young adults with an unknown origin of coronary artery lesions. In addition to systemic immunosuppressive treatment, other measures including antiplatelet and anticoagulation therapy, should be initiated; however, determining the optimal time to perform the procedures such as intervention or surgical operations, is still challenging.

13.
Front Endocrinol (Lausanne) ; 11: 610519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33335513

RESUMO

Purpose: Acromegaly is a rare, intractable endocrine disease. We aimed to describe the patient characteristics, diagnostic delays, treatment patterns, treatment outcomes, comorbidities and treatment costs of acromegaly in China. Methods: This is a nationwide cross-sectional study. Patients diagnosed with and treated for acromegaly between 1996 and 2019 across China were surveyed via the Chinese Association of Patients with Acromegaly platform. Results: In total, 473 patients (58.8% females, mean age at diagnosis: 39.4±9.5 years) were included. The median disease duration was 3 years. The most common symptoms were extremity enlargement (91.8%) and facial changes (90.1%). Overall, 63.0% of patients experienced diagnostic delays within healthcare systems; 63.8% of the delays were <1 year. The most common first-line therapy was surgery with a transsphenoidal (76.1%) or transcranial approach (3.2%). Somatostatin analogues or dopamine agonists were administered in 20.5% of the patients as first-line therapies and in 41.7% as adjuvant therapies. Radiotherapy was performed in 32.1% of patients, 99.3% of whom received radiotherapy as an adjuvant therapy. After a median 5-year follow-up, 46.2% achieved biochemical control. Comorbidities were reported in 88.2% of the patients at follow-up; memory deterioration and thyroid nodules were the most common. Controlled patients had greater improvements in symptoms and comorbidities during follow-up than uncontrolled patients. The annual per-capita cost-of-treatment was $11013 in 2018, with medical treatments being the largest contributor (67%). Medical insurance covered 47.2% of all treatment costs. Conclusion: This study provides the first comprehensive description of real-world acromegaly data in China, serving as a basis for future population-based studies.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33162306

RESUMO

OBJECTIVE: The aim of this study was to investigate the incidence, clinical presentation, cardiovascular (CV) complications, and mortality risk of myocardial injury on admission in critically ill intensive care unit (ICU) inpatients with COVID-19. DESIGN: A single-center, retrospective, observational study. SETTING: A newly built ICU in Tongji hospital (Sino-French new city campus), Huazhong University of Science and Technology, Wuhan, China. PARTICIPANTS: Seventy-seven critical COVID-19 patients. INTERVENTIONS: Patients were divided into a myocardial injury group and nonmyocardial injury group according to the on-admission levels of high-sensitivity cardiac troponin I. MEASUREMENTS AND MAIN RESULTS: Demographic data, clinical characteristics, laboratory tests, treatment, and clinical outcome were evaluated, stratified by the presence of myocardial injury on admission. Compared with nonmyocardial injury patients, patients with myocardial injury were older (68.4 ± 10.1 v 62.1 ± 13.5 years; p = 0.02), had higher prevalence of underlying CV disease (34.1% v 11.1%; p = 0.02), and in-ICU CV complications (41.5% v 13.9%; p = 0.008), higher Acute Physiology and Chronic Health Evaluation II scores (20.3 ± 7.3 v 14.4 ± 7.4; p = 0.001), and Sequential Organ Failure Assessment scores (7, interquartile range (IQR) 5-10 v 5, IQR 3-6; p < 0.001). Myocardial injury on admission increased the risk of 28-day mortality (hazard ratio [HR], 2.200; 95% confidence interval [CI] 1.29 to 3.74; p = 0.004). Age ≥75 years was another risk factor for mortality (HR, 2.882; 95% CI 1.51-5.50; p = 0.002). CONCLUSION: Critically ill patients with COVID-19 had a high risk of CV complications. Myocardial injury on admission may be a common comorbidity and is associated with severity and a high risk of mortality in this population.

15.
Medicine (Baltimore) ; 99(47): e23184, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217825

RESUMO

Lipid abnormalities are an important cause of premature atherosclerosis in patients with systemic lupus erythematosus (SLE). This longitudinal study investigates the changes in lipid profile and arterial stiffness with SLE disease activity index (SLEDAI) reduction.Fifty one female SLE patients with baseline SLEDAI ≥ 6 and SLEDAI reduction >3 at 1-year follow-up were included. Neutrophil-to-lymphocyte ratio (NLR), erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and mean brachial-ankle pulse wave velocity (baPWV) were measured and compared between baseline and 1-year follow-up. Correlations between inflammation biomarkers, SLEDAI, mean baPWV and lipid profile were assessed.We observed significant decreases in ESR, mean baPWV, TG and TC to HDL-C ratio compared with baseline at 1-year follow up, while HDL-C, hsCRP, and NLR were not significantly changed. Significant correlations were found between the reductions in ESR and TG, and SLEDAI and mean baPWV, with adjustment to age, disease duration, blood pressure, and medications (prednisone, immunosuppressants and ARB/ACEI).SLE patients experiencing SLEDAI reductions showed improvements in arterial stiffness. This finding may provide insight into the beneficial effects of reducing SLEDAI on atherosclerosis risk in SLE.

16.
Cell Death Dis ; 11(11): 995, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219221

RESUMO

Adrenocortical carcinoma is one of the aggressive malignancies and it originates from the cortex of adrenal gland. Dysregulation of long non-coding RNA plays important roles in the development of adrenocortical carcinoma. Here, we found that lncRNA ASB16-AS1 was down-regulated in adrenocortical carcinoma and ASB16-AS1 functions as tumor suppressor in vitro and in vivo. We then found that IGF1R and CDK6 are regulated by ASB16-AS1 in adrenocortical carcinoma cells by transcriptome RNA sequencing. ASB16-AS1 associates with RNA-binding protein HuR (ELAVL1) as revealed by RNA pull-down following mass spectrometry. Also, ASB16-AS1 inhibits HuR expression post-translationally by promoting its ubiquitination. ASB16-AS1 regulates IGF1R and CDK6 mRNA expression through RNA-binding protein HuR. We then found that inhibition of ASB16-AS1 attenuates the binding of ubiquitin E3 ligase BTRC to HuR and subsequently inhibits HuR protein unbiquitination and degradation. BTRC knock-down could reverse the effect of AB16-AS1 on HuR, CDK6, and IGF1R levels. Collectively, these results demonstrate that ASB16-AS1 regulates adrenocortical carcinoma cell proliferation and tackling the level of ASB16-AS1 may be developed to treat adrenocortical carcinoma.

17.
Value Health ; 23(12): 1580-1591, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33248513

RESUMO

OBJECTIVES: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. METHODS: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. RESULTS: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs $3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001). CONCLUSIONS: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs.

18.
Cerebrovasc Dis ; 49(5): 522-530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33091907

RESUMO

BACKGROUND AND PURPOSE: To compare the risk factors and risk of stroke between lacune and large perivascular spaces (PVSs) in a community-based sample. METHODS: Large PVSs were assessed using 3.0T MRI in a population-based cohort consisting of 1,204 participants. The relationship between cardiovascular risk factors, neuroimaging changes, and incidental stroke risk and the presence of lacune or large PVSs was assessed with univariate and multivariable ordinal logistic regression analysis. RESULTS: Of the 1,204 study participants (55.7 ± 9.3 years, 37.0% men), a total of 347 large PVSs were detected in 235 (19.5%) subjects, while a total of 219 lacunes were detected in 183 subjects (15.2%). The presence of lacunes was found to be significantly associated with age, male gender, hypertension, and diabetes, whereas only age (p < 0.01) and ApoEε4 carrier status (p < 0.01) were related to the presence of large PVSs. Those who had lacunes detected on MRI at baseline had a significant increased risk of stroke (hazard ratio [HR] 4.68; 95% confidence interval [CI], 1.15-19.07) during the 3-year follow-up independent of age, gender, and other vascular risk factors. However, there was no significant relationship between the presence of large PVSs and incident stroke (HR 3.84; 95% CI, 0.82-18.04). CONCLUSIONS: The lack of association between large PVSs and cardiovascular risk factors or risk of stroke indicated a nonvascular pathogenic mechanism underlying large PVSs, suggesting the importance of distinguishing large PVSs from lacunes in clinical practice.


Assuntos
Artérias Cerebrais/diagnóstico por imagem , Sistema Glinfático/diagnóstico por imagem , Imagem por Ressonância Magnética , Acidente Vascular Cerebral Lacunar/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral Lacunar/etiologia
19.
Mol Med ; 26(1): 97, 2020 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121429

RESUMO

BACKGROUND: COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients' outcome. METHODS: This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. RESULTS: The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P < 0.001). However, no statistical difference in MIP1α between the two groups was found. The analysis of dynamic changes showed that these indicators remarkably increased in patients with poor prognosis. Since the selected patients were severe or critically ill, no significant difference was observed between survival and death. CONCLUSIONS: IP-10 and MCP-1 are biomarkers associated with the severity of COVID-19 disease and can be related to the risk of death in COVID-19 patients.


Assuntos
Quimiocina CCL2/sangue , Quimiocina CXCL10/sangue , Infecções por Coronavirus/complicações , Síndrome da Liberação de Citocina/complicações , Coagulação Intravascular Disseminada/complicações , Pneumonia Viral/complicações , Embolia Pulmonar/complicações , Insuficiência Respiratória/complicações , Proteínas Adaptadoras de Transdução de Sinal/sangue , Idoso , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Síndrome da Liberação de Citocina/diagnóstico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Coagulação Intravascular Disseminada/diagnóstico , Coagulação Intravascular Disseminada/mortalidade , Coagulação Intravascular Disseminada/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Prognóstico , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/mortalidade , Embolia Pulmonar/virologia , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/virologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Análise de Sobrevida
20.
Artigo em Inglês | MEDLINE | ID: mdl-33079177

RESUMO

CONTEXT: Quality of life (QoL) continues to be impaired in acromegaly after treatment. OBJECTIVE: We conducted the first nationwide survey assessing QoL status among Chinese patients with treated acromegaly and explored correlations with clinical parameters, treatment modalities and outcomes. DESIGN: Cross-sectional study. SETTING: Survey via Chinese Association of Patients with Acromegaly (CAPA) online platform. PATIENTS: Treated patients from CAPA. MAIN OUTCOME MEASURES: QoL was assessed using acromegaly QoL questionnaire (AcroQoL), five-level EuroQoL five-dimensional questionnaire (EQ-5D-5L), and 12-item short-form health survey questionnaire (SF-12). RESULTS: Complete, valid questionnaires from 327 patients (mean age: 39.2 years, 61.5% females) at a mean of 10 years after treatment were included. Biochemical control was satisfied in 52.9% of these patients. The controlled patients had significantly better QoL than the uncontrolled patients in all AcroQoL dimensions, most SF-12 dimensions, and pain/discomfort and anxiety/depression dimensions of the EQ-5D-5L. Patients with either controlled or uncontrolled acromegaly had significantly worse QoL than the age- and sex-adjusted population reference in most SF-12 dimensions except for physical functioning. More acromegaly-associated symptoms and comorbidities at follow-up were independent risk factors for decreased QoL across all questionnaires. Medical treatment, especially with somatostatin analogs (SSAs), and radiotherapy were predictors of worse QoL. Female patients had lower scores of physical-related QoL than male patients. CONCLUSIONS: Our study suggests that biochemical control improved but did not normalize QoL in acromegaly. Numbers of symptoms and comorbidities at follow-up, sex, radiotherapy, and medical treatment with SSAs were factors determining QoL of patients with treated acromegaly.

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