DONA ORA
Pubblicazioni recenti - cardiovascular disease
-
Brachyury engineers cardiac repair competent stem cells.
Stem Cells Transl Med2020 Oct;():. doi: 10.1002/sctm.20-0193.
Li Mark, Yamada Satsuki, Shi Ao, Singh Raman Deep, Rolland Tyler J, Jeon Ryounghoon, Lopez Natalia, Shelerud Lukas, Terzic Andre, Behfar Atta,
Abstract
To optimize the regenerative proficiency of stem cells, a cardiopoietic protein-based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of the current stem cell enhancement protocol. To this end, the microencapsulated-modified-mRNA (M RNA) technique was here applied to introduce early cardiogenic genes into human adipose-derived mesenchymal stem cells (AMSCs). A single mesodermal transcription factor, Brachyury, was sufficient to trigger high expression of cardiopoietic markers, Nkx2.5 and Mef2c. Engineered cardiopoietic stem cells (eCP) featured a transcriptome profile distinct from pre-engineered AMSCs. In?vitro, eCP demonstrated protective antioxidant capacity with enhanced superoxide dismutase expression and activity; a vasculogenic secretome driving angiogenic tube formation; and macrophage polarizing immunomodulatory properties. In?vivo, in a murine model of myocardial infarction, intramyocardial delivery of eCP (600?000 cells per heart) improved cardiac performance and protected against decompensated heart failure. Thus, heart repair competent stem cells, armed with antioxidant, vasculogenic, and immunomodulatory traits, are here engineered through a protein-independent single gene manipulation, expanding the available regenerative toolkit.
© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.
Guarda su PubMed
-
Social deprivation and one-year survival after stroke: a prospective cohort study.
Eur J Neurol2020 Oct;():. doi: 10.1111/ene.14614.
Béjot Yannick, Bourredjem Abderrahmane, Mimeau Emmanuelle, Joux Julien, Lannuzel Annie, Misslin-Tritsch Caroline, Bonithon-Kopp Claire, Rochemont Devi, Nacher Mathieu, Cabie André, Lalanne Mistrih Marie-Laure, Fournel Isabelle, ,
Abstract
BACKGROUND:
Social deprivation may have a deleterious influence on post-stroke outcomes, but available data in the literature are mixed.
AIM:
The aim of this cohort study was to evaluate the impact of social deprivation on one-year survival in patients with first-ever stroke.
METHODS:
Social deprivation was assessed at individual level with the EPICES score, a validated multidimensional questionnaire, in 1312 patients with ischemic stroke (IS), and 228 patients with spontaneous intracerebral hemorrhage (ICH), who were prospectively enrolled in six French study centers. Baseline characteristics including stroke severity and prestroke functional status were collected. Multivariable Cox models were generated to evaluate the associations between social deprivation and survival at 12 months in IS and ICH separately.
RESULTS:
A total of 819 patients (53.2%) were socially deprived (EPICES score?30.17). In IS, mortality at 12 months was higher in deprived than in non-deprived patients (16% versus 11%, p=0.006). In multivariable analyses, there was no association between deprivation and death occurring within the first 90 days following IS (adjusted hazard ratio [aHR]=0.81, 95% CI:0.54-1.22, p=0.32). In contrast, an excess in mortality was observed between 90 days and 12 months in deprived compared with non-deprived patients (aHR=1.97; 95%CI:1.14-3.42, p=0.016). In patients with ICH, mortality at 12 months did not significantly differ according to deprivation status.
CONCLUSIONS:
Social deprivation was associated with delayed mortality in ischemic stroke patients only, and, although the exact underlying mechanisms are still to be identified, our findings suggest that deprived patients in particular may benefit from an optimization of post-stroke care.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Radiographic features and poor prognostic factors of interstitial lung disease with nivolumab for non-small cell lung cancer.
Cancer Sci2020 Oct;():. doi: 10.1111/cas.14710.
Saito Yoshinobu, Sasaki Shinichi, Oikado Katsunori, Tominaga Junya, Sata Masafumi, Sakai Fumikazu, Kato Terufumi, Iwasawa Tae, Kenmotsu Hirotsugu, Kusumoto Masahiko, Baba Tomohisa, Endo Masahiro, Fujiwara Yutaka, Sugiura Hiroaki, Yanagawa Noriyo, Ito Yoshihiko, Sakamoto Takahiko, Ohe Yuichiro, Kuwano Kazuyoshi,
Abstract
Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This post-marketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an Expert Central Review Committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ?60 days from start of nivolumab treatment to onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, 3 had peritumoral-GGO, and 5 had a change in radiographic pattern from non-DAD at onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ?60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Alopecia and Gray Hair Are Associated with COVID-19 Severity.
Exp Dermatol2020 Oct;():. doi: 10.1111/exd.14220.
Ramos Paulo Müller, Ianhez Mayra, Miot Hélio Amante,
Abstract
Individual vulnerability to severe acute respiratory syndrome due to COVID-19 has been associated with age and some comorbidities, such as hypertension, diabetes, and cardiovascular disease. Men have an increased risk for severe disease; conversely, prepubescent males appear to be protected.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Integrating neuronal involvement into the immune and genetic paradigm of vitiligo.
Clin Exp Dermatol2020 Oct;():. doi: 10.1111/ced.14490.
Al Abadie M S, Gawkrodger D J,
Abstract
In this review we show how the neuronal theory is relevant to the convergence theory for the mechanism causing vitiligo, especially the segmental type. Neuropetides and neurotransmitters, e.g. neuropeptide-Y and dopamine, can be central to the pathological mechanisms of melanocyte destruction. They link into a bidirectional network connecting cutaneous nerves, the neuro-endocrine axis, and the immune system, and, through their local influence on cutaneous inflammation, to the antigen-specific regulatory T cells and the chemokine ligand type 9 (CXCL9)/ chemokine receptor type 1 (CXCR1) axis that are thought to be the final pathway for melanocyte destruction.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
QTc interval prolongation and life-threatening arrhythmias during hospitalization in patients with COVID-19. Results from a multi-center prospective registry.
Clin Infect Dis2020 Oct;():. doi: ciaa1578.
Santoro Francesco, Monitillo Francesco, Raimondo Pasquale, Lopizzo Agostino, Brindicci Gaetano, Gilio Michele, Musaico Francesco, Mazzola Michele, Vestito Domenico, Di Benedetto Rossella, Abumayyaleh Mohammad, El-Battrawy Ibrahim, Santoro Carmen Rita, Di Martino Luigi Flavio Massimiliano, Akin Ibrahim, De Stefano Giulio, Fiorilli Rosario, Cannone Michele, Saracino Annalisa, Angarano Salvatore, Carbonara Sergio, Grasso Salvatore, Di Biase Luigi, Brunetti Natale Daniele,
Abstract
BACKGROUND:
Prolonged QTc interval and life-threatening arrhythmias (LTA) are potential drug induced complications previously reported with antimalarial, antivirals and antibiotics.
OBJECTIVES:
To evaluate prevalence and predictors of QTc interval prolongation and incidence of LTA during hospitalization for COVID-19 among patients with normal admission QTc.
METHODS:
110 consecutive patients were enrolled in a multicenter international registry. 12-lead ECG was performed at admission, after 7 and 14 days; QTc values were analyzed.
RESULTS:
Fifteen (14%) patients developed a prolonged-QTc (pQT) after 7 days (mean QTc increase 66±20msec, +16%, p<0.001); these patients were older, had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, lower platelet count. QTc increase was inversely proportional to baseline QTc levels and leukocyte count and directly to basal heart rates(p<0.01).At multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate and dual antiviral therapy, age(OR 1.06, 95% C.I. 1.00-1.13, p<0.05), basal heart rate(OR 1.07, 95% C.I. 1.02-1.13, p<0.01) and dual antiviral therapy(OR 12.46, 95% C.I. 2.09-74.20, p<0.1) were independent predictors of QT-prolongation.Incidence of LTA during hospitalization was 3.6%. One patient experienced cardiac arrest and three non-sustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of mortality rate.
CONCLUSIONS:
After 7 days of hospitalization, 14% of patients with Covid-19 developed pQTc; age, basal heart rate and dual antiviral therapy were found as independent predictor of pQTc. Life threatening arrhythmias have an incidence of 3.6% and were associated with poor outcome.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Guarda su PubMed
-
The sodium-glucose cotransporter 2 inhibitor tofogliflozin prevents diabetic kidney disease progression in type 2 diabetic mice.
FEBS Open Bio2020 Oct;():. doi: 10.1002/2211-5463.13014.
Li Zi, Murakoshi Maki, Ichikawa Saki, Koshida Takeo, Adachi Eri, Suzuki Chigure, Ueda Seiji, Gohda Tomohito, Suzuki Yusuke,
Abstract
Trials on cardiovascular and renal outcomes in patients with type 2 diabetes have consistently demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of diabetic kidney disease (DKD) progression. However, their renal protective mechanisms have yet to be completely understood and the effect on albuminuria reduction in animal models is controversial. Here, we investigated these issues using KK and KK-A mice as a control (CTRL) and as a model for type 2 diabetes (DKD), respectively. KK-A mice were treated with 0.015% tofogliflozin, which is an SGLT2 inhibitor, starting at seven weeks of age for eight weeks. Compared with the CTRL mice, the DKD mice had higher HbA1c levels and albuminuria. Although tofogliflozin treatment significantly lowered HbA1c levels, it did not reverse albuminuria. Tofogliflozin treatment enhanced damage in both the glomerular (i.e., enlarged mesangial area, increased foot process effacement rate, and decreased number of WT-1-positive cells) and tubulointerstitial (increased protein levels of KIM-1 and MCP-1, increased number of macrophages, and abnormal mitochondrial morphology) areas. Our results suggest that tofogliflozin may prevent glomerular and tubulointerstitial damage, partly by ameliorating hyperglycemia, renal inflammation, and abnormal mitochondrial morphology.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Interactive editing of virtual chordae tendineae for the simulation of the mitral valve in a decision support system.
Int J Comput Assist Radiol Surg2020 Oct;():. doi: 10.1007/s11548-020-02230-y.
Walczak Lars, Tautz Lennart, Neugebauer Mathias, Georgii Joachim, Wamala Isaac, Sündermann Simon, Falk Volkmar, Hennemuth Anja,
Abstract
PURPOSE:
Decision support systems for mitral valve disease are an important step toward personalized surgery planning. A simulation of the mitral valve apparatus is required for decision support. Building a model of the chordae tendineae is an essential component of a mitral valve simulation. Due to image quality and artifacts, the chordae tendineae cannot be reliably detected in medical imaging.
METHODS:
Using the position-based dynamics framework, we are able to realistically simulate the opening and closing of the mitral valve. Here, we present a heuristic method for building an initial chordae model needed for a successful simulation. In addition to the heuristic, we present an interactive editor to refine the chordae model and to further improve pathology reproduction as well as geometric approximation of the closed valve.
RESULTS:
For evaluation, five mitral valves were reconstructed based on image sequences of patients scheduled for mitral valve surgery. We evaluated the approximation of the closed valves using either just the heuristic chordae model or a manually refined model. Using the manually refined models, prolapse was correctly reproduced in four of the five cases compared to two of the five cases when using the heuristic. In addition, using the editor improved the approximation in four cases.
CONCLUSIONS:
Our approach is suitable to create realistically parameterized mitral valve apparatus reconstructions for the simulation of normally and abnormally closing valves in a decision support system.
Guarda su PubMed
-
Syphilitic aortitis: chronic left coronary ostial occlusion and aortic regurgitation with aortitis.
Gen Thorac Cardiovasc Surg2020 Oct;():. doi: 10.1007/s11748-020-01523-y.
Nomura Ryota, Yamazaki Fumio, Egawa Yuki,
Abstract
Before the discovery of penicillin, tertiary syphilis was the most common cause of thoracic aneurysms, but now cardiovascular syphilis is a clinical rarity in developed countries. We report a case of 69-year-old man who presented with sudden onset breathlessness that worsened insidiously for 2 months. Diagnosis of syphilitic aortitis was confirmed by laboratory findings, contrast computed tomography, echocardiography and coronary angiography. The patient underwent successful coronary artery bypass graft, aortic valve replacement and ascending aortic replacement. A high level of suspicion and awareness is needed for the diagnosis of the now rare disease.
Guarda su PubMed
-
Elevated high-sensitivity troponin T levels at 1-year follow-up are associated with increased long-term mortality after TAVR.
Clin Res Cardiol2020 Oct;():. doi: 10.1007/s00392-020-01759-x.
Seoudy Hatim, Lambers Moritz, Winkler Vincent, Dudlik Linnea, Freitag-Wolf Sandra, Frank Johanne, Kuhn Christian, Rangrez Ashraf Yusuf, Puehler Thomas, Lutter Georg, Bramlage Peter, Frey Norbert, Frank Derk,
Abstract
BACKGROUND:
Elevated pre-procedural high-sensitivity troponin T (hs-TnT) levels predict adverse outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). It is unknown whether elevated troponin levels still provide prognostic information during follow-up after successful TAVR. We evaluated the long-term implications of elevated hs-TnT levels found at 1-year post-TAVR.
METHODS AND RESULTS:
The study included 349 patients who underwent TAVR for severe AS from 2010-2019 and for whom 1-year hs-TnT levels were available. Any required percutaneous coronary interventions were performed?>?1 week before TAVR. The primary endpoint was survival time starting at 1-year post-TAVR. Optimal hs-TnT cutoff for stratifying risk, identified by ROC analysis, was 39.4 pg/mL. 292 patients had hs-TnT??300 pg/mL, male sex, an eGFR < 60 mL/min/1.73 m and chronic obstructive pulmonary disease as independent risk factors for long-term mortality after TAVR.
CONCLUSIONS:
Elevated hs-TnT concentrations at 1-year after TAVR were associated with a higher long-term mortality.
Guarda su PubMed
-
Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes: secondary analyses from a randomised controlled trial.
Diabetologia2020 Oct;():. doi: 10.1007/s00125-020-05300-7.
Limonte Christine P, Zelnick Leila R, Ruzinski John, Hoofnagle Andrew N, Thadhani Ravi, Melamed Michal L, Lee I-Min, Buring Julie E, Sesso Howard D, Manson JoAnn E, de Boer Ian H,
Abstract
AIMS/HYPOTHESIS:
Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes.
METHODS:
This study reports pre-specified secondary outcomes of the Vitamin D and Omega-3 Trial to Prevent and Treat Diabetic Kidney Disease, in which 1312 US adults with type 2 diabetes and without known cardiovascular disease, malignancy, or end-stage kidney disease were randomised using computer-generated random numbers in blocks of eight to vitamin D (2000 IU/day) vs placebo and n-3 fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]; 1 g/day) vs placebo in a 2?×?2 factorial design. Participants, examiners, and researchers assessing outcomes were blinded to intervention assignment. We measured serum IL-6, high-sensitivity C-reactive protein (hsCRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at baseline and after 2 and 5 years.
RESULTS:
A total of 333 participants were randomised to vitamin D and placebo n-3 fatty acids, 289 to n-3 fatty acids and placebo vitamin D, 370 to vitamin D and n-3 fatty acids, and 320 to 2 placebos; 989 (75%) and 934 (71%) participants returned blood samples at 2 and 5 years, respectively. Participants had a mean age of 67.6 years (46% women). Overall, baseline geometric means of IL-6, hsCRP and NT-proBNP were 1.2 pg/ml, 1.9 mg/l and 262 ng/l, respectively. After 5 years, mean IL-6 and hsCRP remained within 6% of their baseline values while mean NT-proBNP increased by 55% overall. Compared with placebo, participants assigned to vitamin D had a 1.24-fold greater increase in NT-proBNP over 5 years (95% CI 1.09, 1.41; p?=?0.003), while IL-6 and hsCRP did not have a significant difference in change. Comparing n-3 fatty acids with placebo, there was no significant difference in change in IL-6, hsCRP or NT-proBNP. No heterogeneity was observed in subgroup analyses accounting for baseline eGFR, urine albumin to creatinine ratio, initial biomarker concentration, 25-hydroxyvitamin D level or EPA+DHA index.
CONCLUSIONS/INTERPRETATION:
Among adults with type 2 diabetes, supplementation with vitamin D or n-3 fatty acids did not reduce IL-6, hsCRP or NT-proBNP over 5 years.
TRIAL REGISTRATION:
ClinicalTrials.gov NCT01684722 FUNDING: The study was funded by grant R01DK088762 from the National Institute of Diabetes and Digestive and Kidney Diseases. Graphical abstract.
Guarda su PubMed
-
Study design, result posting and publication of late-stage cardiovascular trials.
Eur Heart J Qual Care Clin Outcomes2020 Oct;():. doi: qcaa080.
Kapelios Chris J, Naci Huseyin, Vardas Panos E, Mossialos Elias,
Abstract
AIMS:
Pre-registration of study protocols in accessible databases is required for publication of study results in high-impact medical journals. Nonetheless, data on characteristics of clinical trials registered in these databases and their outcome, in terms of result reporting and publication are limited.
METHODS AND RESULTS:
We searched for interventional, late-phase cardiovascular disease (CVD) studies in adults registered in Clinicaltrials.gov. first posted after 1/1/2013 and completed up to 31/12/2018. Data on study design, result reporting and publication were collected, and potential associations with a pre-defined set of explanatory factors were examined.In total, 250 CVD trials were included in the analysis. Of these, 193 (77.2%) were randomized studies, 99 (39.6%) open label designs, and 126 (50.4%) had industry as main sponsor. 179 trials (71.6%) evaluated the effect of drugs and 27 (10.8%) evaluated devices. The most common primary outcomes were non-clinical endpoints (76.0%), with only 17% of studies evaluating clinical endpoints. Industry-funded trials focused on patent-protected drugs and devices more often than non-industry-funded trials (72.0% vs. 30.6%, P?
CONCLUSION:
Among late-stage cardiovascular trials only 1/4 had results posted on clinicaltrials.gov and <50% had results published. Industry sponsors were more likely to invest in research on patent-protected drugs and devices than were non-industry sponsors. Industry-sponsored studies were more likely to have their results posted, but less likely to have their results published in the scientific literature.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
Guarda su PubMed
-
Caloric restriction mimetics for the treatment of cardiovascular diseases.
Cardiovasc Res2020 Oct;():. doi: cvaa297.
Sciarretta Sebastiano, Forte Maurizio, Castoldi Francesca, Frati Giacomo, Versaci Francesco, Sadoshima Junichi, Kroemer Guido, Maiuri Maria Chiara,
Abstract
Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodeling in animal models of aging, mechanical overload, chronic myocardial ischemia, as well as in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischemia-reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email: journals.permissions@oup.com.
Guarda su PubMed
-
The Association between Occupational Categories and Incidence of Cardiovascular Events: A Cohort Study in Iranian Male Population.
Int J Occup Environ Med2020 Oct;11(4):179-187. doi: 10.34172/ijoem.2020.2053.
Ghahramani Rahil, Kermani-Alghoraishi Mohammad, Roohafza Hamidreza, Bahrani Saeide, Talaei Mohammad, Dianatkhah Minoo, Sarrafzadegan Nizal, Sadeghi Masoumeh,
Abstract
BACKGROUND:
Besides the traditional cardiovascular risk factor, some novel risk factors like occupation and career can play an important role in cardiovascular disease (CVDs) incidence.
OBJECTIVE:
To assess the association between occupational categories and their positions with cardiovascular events (CVEs) in an Iranian male population.
METHODS:
We followed 2134 men aged 35-65 years for 14 years during the Isfahan Cohort Study (2001-2015) for CVEs including ischemic heart disease and stroke. Firstly, Occupations were classified into 10 categories of International Standard Classification of Occupation (ISCO). Each category was then classified into one of the 4 pre-specified categories, namely high/low skilled white collars and high/low skilled blue collars. White-collar workers referred to managerial and professional workers in contrast with blue collar workers, whose job requires manual labor.
RESULTS:
The mean age of studied participants was 46.9 (SD 8.3) years. 286 CVE incidents were recorded; unstable angina had the highest rate (46%); fatal stroke, the lowest (3%). There were no significant difference was observed between white and blue collars in terms of CVE incidence, as well as their high and low skilled subgroups. Hazard ratio analysis indicated a significantly higher risk of CVEs only for low-skilled white-collar workers (crude HR 1.47, 95% CI 1.01 to 2.13); this was not significant after adjustment for confounding variables.
CONCLUSION:
There is no association between occupational categories and incidence of cardiovascular events among Iranian male population.
Guarda su PubMed
-
Novel mutations of TCTN3/LTBP2 with cellular function changes in congenital heart disease associated with polydactyly.
J Cell Mol Med2020 Oct;():. doi: 10.1111/jcmm.15950.
Chen Huan-Xin, Yang Zi-Yue, Hou Hai-Tao, Wang Jun, Wang Xiu-Li, Yang Qin, Liu Lin, He Guo-Wei,
Abstract
Congenital heart disease (CHD) associated with polydactyly involves various genes. We aimed to identify variations from genes related to complex CHD with polydactyly and to investigate the cellular functions related to the mutations. Blood was collected from a complex CHD case with polydactyly, and whole exome sequencing (WES) was performed. The CRISPR/Cas9 system was used to generate human pluripotent stem cell with mutations (hPSCs-Mut) that were differentiated into cardiomyocytes (hPSC-CMs-Mut) and analysed by transcriptomics on day 0, 9 and 13. Two heterozygous mutations, LTBP2 (c.2206G>A, p.Asp736Asn, RefSeq NM_000428.2) and TCTN3 (c.1268G>A, p.Gly423Glu, RefSeq NM_015631.5), were identified via WES but no TBX5 mutations were found. The stable cell lines of hPSCs-LTBP2 /TCTN3 were constructed and differentiated into hPSC-CMs-LTBP2 /TCTN3 . Compared to the wild type, LTBP2 mutation delayed the development of CMs. The TCTN3 mutation consistently presented lower rate and weaker force of the contraction of CMs. For gene expression pattern of persistent up-regulation, pathways in cardiac development and congenital heart disease were enriched in hPSCs-CM-LTBP2 , compared with hPSCs-CM-WT. Thus, the heterozygous mutations in TCTN3 and LTBP2 affect contractility (rate and force) of cardiac myocytes and may affect the development of the heart. These findings provide new insights into the pathogenesis of complex CHD with polydactyly.
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Guarda su PubMed
-
Atypical 7q11.23 deletions excluding ELN gene result in Williams-Beuren syndrome craniofacial features and neurocognitive profile.
Am J Med Genet A2020 Oct;():. doi: 10.1002/ajmg.a.61937.
Alesi Viola, Loddo Sara, Orlando Valeria, Genovese Silvia, Di Tommaso Silvia, Liambo Maria Teresa, Pompili Daniele, Ferretti Daniele, Calacci Chiara, Catino Giorgia, Falasca Roberto, Dentici Maria Lisa, Novelli Antonio, Digilio Maria Cristina, Dallapiccola Bruno,
Abstract
Williams-Beurens syndrome (WBS) is a rare genetic disorder caused by a recurrent 7q11.23 microdeletion. Clinical characteristics include typical facial dysmorphisms, weakness of connective tissue, short stature, mild to moderate intellectual disability and distinct behavioral phenotype. Cardiovascular diseases are common due to haploinsufficiency of ELN gene. A few cases of larger or smaller deletions have been reported spanning towards the centromeric or the telomeric regions, most of which included ELN gene. We report on three patients from two unrelated families, presenting with distinctive WBS features, harboring an atypical distal deletion excluding ELN gene. Our study supports a critical role of CLIP2, GTF2IRD1, and GTF2I gene in the WBS neurobehavioral profile and in craniofacial features, highlights a possible role of HIP1 in the autism spectrum disorder, and delineates a subgroup of WBS individuals with an atypical distal deletion not associated to an increased risk of cardiovascular defects.
© 2020 Wiley Periodicals LLC.
Guarda su PubMed
-
Prognostic value of pre-treatment cardiovascular biomarkers in head and neck squamous cell carcinoma.
Oral Dis2020 Oct;():. doi: 10.1111/odi.13691.
de Oliveira Karine Gadioli, Thebit Marcela Marçal, Andrade Tadeu Uggere, Campos Fabiana Vasconcelos, Podestá Jose Roberto Vasconcelos, Von Zeidler Sandra Lucia Ventorin, Bissoli Nazaré Souza, Gouvea Sonia Alves,
Abstract
OBJECTIVES:
To examine the prognostic significance of pre-treatment C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) levels on all-cause mortality three years after head and neck squamous cell carcinoma (HNSCC) diagnosis.
SUBJECTS AND METHODS:
Data from 118 consecutive HNSCC patients, treated between 2012 and 2015, were evaluated prospectively. The impact of CRP, high-sensitive (hs)-cTnT and NT-proBNP levels on the 3-year overall survival was estimated using the Kaplan-Meier method and Cox proportional hazard models.
RESULTS:
During the 36-month follow-up, 37 patients (31.35%) died. Multivariate analysis revealed that elevated CRP (Hazard ratio: 3.71, 95% CI: 1.44 - 9.53, P = 0.007) and NT-proBNP levels (Hazard ratio: 5.04, 95% CI: 2.02 - 12.55, P = 0.001) were associated to negative prognosis, independent on age, sex, smoking and alcohol status, TNM classification, tumor site, body mass index (BMI), systolic blood pressure (SBP), and treatment modality (except for radiotherapy). hs-cTnT had no influence over the prognosis, but it was correlated with TNM classification and SBP. CRP was significantly correlated with BMI and TNM classification, and NT-proBNP with SBP and hs-cTnT.
CONCLUSIONS:
Pre-treatment CRP and NT-proBNP levels were identified as independent prognostic markers for poor clinical outcome three years after HNSCC diagnosis.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
National Analysis of 30-Day Readmission Following Inpatient Sinus Surgery for Chronic Rhinosinusitis.
Laryngoscope2020 Oct;():. doi: 10.1002/lary.29117.
Khoury Habib, Bellamkonda Nikhil, Benharash Peyman, Lee Jivianne T, Wang Marilene B, Suh Jeffrey D,
Abstract
OBJECTIVES:
To characterize the incidence, causes, risk factors, and costs of 30-day readmission after inpatient functional endoscopic sinus surgery (FESS) for patients with chronic rhinosinusitis.
STUDY DESIGN:
Retrospective cohort study.
METHODS:
The Nationwide Readmissions Database was used to characterize readmission after inpatient sinus surgery for chronic rhinosinusitis from 2015 to 2017. International Classification of Disease codes were used to identify the patient population, which included 5,644 patients. Incidence, causes, costs, and predictors of readmission were analyzed and determined.
RESULTS:
Among 6,386 patients who underwent inpatient FESS, 742 (11.6%) were readmitted within 30?days of discharge. On univariate analysis, patients who were readmitted were more commonly older than 70?years (23.3% vs. 16.2%); had a higher burden of comorbidities including chronic kidney disease (15.0% vs. 7.8%), diabetes (25.6% vs. 20.4%), and hypertension (13.5% vs. 8.5%); had a greater rate of postoperative complications (20.7% vs. 12.2%); and had a longer length of stay (12.4 vs. 6.9?days) compared to patients who were not readmitted. Readmissions cost an additional $27,141 per patient. On multivariable analysis, age greater than 70?years, Medicaid insurance, several comorbidities, prolonged length of stay, postoperative neurologic complications, and lower hospital volume were independent predictors of 30-day readmission. The most common cause for readmission was infection (36.3%).
CONCLUSION:
Readmission following inpatient FESS is not uncommon. Identification and management of preoperative comorbidities, optimized patient selection for inpatient surgery, and thorough postoperative discharge care may improve patient outcomes and decrease healthcare expenditures.
LEVEL OF EVIDENCE:
3 Laryngoscope, 2020.
© 2020 American Laryngological, Rhinological and Otological Society Inc, ?The Triological Society? and American Laryngological Association (ALA).
Guarda su PubMed
-
Association of Hydroxychloroquine Use with Reduced Risk of Incident Atrial Fibrillation in Lupus.
Arthritis Care Res (Hoboken)2020 Oct;():. doi: 10.1002/acr.24494.
Gupta Alisha, Shields Kelly J, Manzi Susan, Wasko Mary Chester, Sharma Tarun S,
Abstract
OBJECTIVE:
To study the relationship between hydroxychloroquine (HCQ) use and new onset atrial fibrillation in patients with systemic lupus erythematosus (SLE).
METHODS:
A retrospective cohort of adult SLE patients from Dec 1, 2014 to May 30, 2017 was constructed. Patients were categorized as either HCQ users or non-users. The primary outcome was incident atrial fibrillation; secondary outcomes included incident ventricular arrhythmias (composite of ventricular tachycardia (VT), ventricular fibrillation (VF), or torsades de pointes). Outcomes were adjudicated by review of the electronic health record. Statistical analyses included simple and multivariable logistic regression analyses to estimate the association between HCQ use and incident atrial fibrillation after adjusting for relevant confounders. Propensity score matching analysis was completed.
RESULTS:
Our study included 1647 patients with SLE, of which 917 were HCQ users and 730 were non-users. A total of 23 atrial fibrillation events occurred, 3 in HCQ users and 20 in non-users. Logistic regression analysis showed an OR of 0.12 (95% CI 0.034-0.39, p=0.0005) for incident atrial fibrillation, and 2.39 (95% CI 0.25-23, p=0.45) for ventricular arrhythmias. Results remained significant in the fully adjusted and propensity score matched models.
CONCLUSION:
In this exploratory study, HCQ use was associated with an 88% decrease in the risk of incident atrial fibrillation in SLE patients. Considering the increased cardiovascular risk in SLE, incorporation of HCQ into the regimen may be beneficial for both disease manifestations and reducing risk of atrial fibrillation. Further studies would be needed to confirm the anti-fibrillatory benefit of this relatively safe and low-cost medication.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
-
Support for increased cardiovascular risk in non-segmental vitiligo among Egyptians: A hospital-based, case-control study.
Pigment Cell Melanoma Res2020 Oct;():. doi: 10.1111/pcmr.12941.
Azzazi Yousra, Mostafa Wedad Z, Sayed Khadiga S, Alhelf Maha, Safwat Miriam, Mahrous Ayman, Lawindi Mona El, Ragab Nanis,
Abstract
BACKGROUND:
Data has been accumulating in the past few years that identify vitiligo as a disorder with systemic implications.
RESULTS AND METHODS:
In this hospital-based, cross-sectional, case-control study, 50 patients with non-segmental vitiligo and 50 age and sex-matched controls underwent analysis of serum lipid profile, oxidative stress biomarkers and carotid duplex. Hydrogen peroxide (H O ) and malondialdehyde (MDA) were significantly higher in patients than controls (p-value < 0.001, < 0.001 respectively), on the other hand total antioxidant capacity (TAC) was significantly lower in patients than controls (p-value= 0.001). A significantly higher percentage of patients had hypercholesterolemia and borderline high, high or very high levels of LDL-C, compared to controls (p-value=0.001 & 0.001 respectively). Atherosclerotic plaques and increased common carotid intima media thickness were significantly detected in patients versus controls.
DISCUSSION:
Results of the present study suggest that a subset of patients with vitiligo are at a higher risk of developing dyslipidemia and atherosclerosis which might increase their future risk for the development of cardiovascular disease. Confirmation of these findings would subsequently influence investigative and the treatment strategies in the management plan of vitiligo patients in the near future.
SIGNIFICANCE:
Vitiligo patients might be at a higher risk of developing dyslipidemia and atherosclerosis which might increase their risk for the development of cardiovascular disease necessitating prophylactic measures to improve prognosis. Our results might influence the investigative and treatment strategies in the management plan of vitiligo patients in the near future.
This article is protected by copyright. All rights reserved.
Guarda su PubMed
