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1.
J Matern Fetal Neonatal Med ; 37(1): 2344718, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38679587

RESUMO

OBJECTIVE: Holoprosencephaly (HPE) is the most common aberration of forebrain development, and it leads to a wide spectrum of developmental and craniofacial anomalies. HPE etiology is highly heterogeneous and includes both chromosomal abnormalities and single-gene defects. METHODS: Here, we report an FGFR1 heterozygous variant detected by prenatal exome sequencing and inherited from the asymptomatic mother, in association with recurrent neurological abnormalities in the HPE spectrum in two consecutive pregnancies. RESULTS: Individuals with germline pathogenic variants in FGFR1 (MIM: 136350) show extensive phenotypic variability, which ranges from asymptomatic carriers to hypogonadotropic hypogonadism, arhinencephaly, Kallmann's syndrome with associated features such as cleft lip and palate, skeletal anomalies, isolated HPE, and Hartsfield syndrome. CONCLUSION: The presented case supports the role of exome sequencing in prenatal diagnosis when fetal midline structural anomalies are suggestive of a genetic etiology, as early as the first trimester of gestation. The profound heterogeneity of FGFR1 allelic disorders needs to be considered when planning prenatal screening even in asymptomatic carriers.


Assuntos
Holoprosencefalia , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos , Humanos , Feminino , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Gravidez , Holoprosencefalia/genética , Holoprosencefalia/diagnóstico , Adulto , Diagnóstico Pré-Natal/métodos , Sequenciamento do Exoma , Ultrassonografia Pré-Natal , Prosencéfalo/anormalidades , Prosencéfalo/embriologia , Heterozigoto
2.
Emerg Radiol ; 30(1): 63-69, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36378395

RESUMO

PURPOSE: The increased utilization, and potential overutilization, of computed tomography pulmonary angiography (CTPA) is a well-recognized issue within emergency departments (EDs). The objective of this study is to determine the impact of performance feedback reports on CTPA ordering behavior among ED physicians. METHODS: We conducted a prospective study of the impact of individualized performance feedback reports on the ordering behavior of physicians working at two high-volume community EDs in Ontario, Canada. We generated individualized reports (or "Dashboards") for each ED physician containing detailed feedback and peer comparison for each physician's CTPA ordering. Our baseline pre-intervention period was January 1 to December 31, 2018, and our intervention period was January 1, 2019, to December 31, 2021. We tracked individual and group ordering behavior through the study period. Our primary outcomes are impact of feedback on (1) overall group ordering rate and (2) overall diagnostic yield. Secondary analysis was done to determine the impact of the intervention on those physicians with the highest CTPA utilization rate. RESULTS: There was no statistically significant difference in the diagnostic yield of the included physicians in either of the years of the intervention period. There was a statically significant increase in the utilization rate for CTPA from 2018 to 2020 and 2021 from 5.9 to 7.9 and 11.4 CTPAs per 1000 ED visits respectively (p < 0.5). CONCLUSION: Our study found no consistent significant impact of individualized feedback and peer comparison on physician ordering of CTPAs. This points to a potentially greater impact of environmental and institutional factors, as opposed to physician-targeted quality improvement measures, on physician ordering behavior.


Assuntos
Embolia Pulmonar , Humanos , Angiografia , Angiografia por Tomografia Computadorizada/métodos , Retroalimentação , Ontário , Estudos Prospectivos , Tomografia
3.
Sci Rep ; 12(1): 568, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022468

RESUMO

Prolongation of cardiac repolarization (QT interval) represents a dangerous and potentially life-threatening electrical event affecting the heart. Thyroid hormones (THs) are critical for cardiac development and heart function. However, little is known about THs influence on ventricular repolarization and controversial effects on QT prolongation are reported. Human iPSC-derived cardiomyocytes (hiPSC-CMs) and multielectrode array (MEA) systems were used to investigate the influence of 3,3',5-triiodo-L-Thyronine (T3) and 3,3',5,5'-tetraiodo-L-Thyronine (T4) on corrected Field Potential Duration (FPDc), the in vitro analog of QT interval, and on local extracellular Action Potential Duration (APD). Treatment with high THs doses induces a significant prolongation of both FPDc and APD, with the strongest increase reached after 24 h exposure. Preincubation with reverse T3 (rT3), a specific antagonist for nuclear TH receptor binding, significantly reduces T3 effects on FPDc, suggesting a TRs-mediated transcriptional mechanism. RNA-seq analysis showed significant deregulation in genes involved in cardiac repolarization pathways, including several QT-interval related genes. In conclusion, long-time administration of high THs doses induces FPDc prolongation in hiPSC-CMs probably through the modulation of genes linked to QT-interval regulation. These results open the way to investigate new potential diagnostic biomarkers and specific targeted therapies for cardiac repolarization dysfunctions.


Assuntos
Regulação da Expressão Gênica , Síndrome do QT Longo/etiologia , Miócitos Cardíacos/fisiologia , Hormônios Tireóideos/fisiologia , Potenciais de Ação , Adolescente , Células Cultivadas , Feminino , Humanos , Células-Tronco Pluripotentes Induzidas
4.
Emerg Radiol ; 29(2): 291-298, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34812977

RESUMO

PURPOSE: To describe the impact of a new institutional Code Stroke protocol on ordering volume of head and neck CT angiographies (CTA), and to determine the number and proportion of these studies that resulted in an endovascular or surgical intervention. METHODS: Clinical and administrative data was collected on all head and neck CTAs ordered within the ED at two high-volume community hospitals and an affiliated urgent care centre during the 6-year period between January 1, 2014, and December 31, 2019. Of those patients who underwent CTA, we identified those who were then transferred to a regional stroke centre for consideration of EVT and those who underwent carotid endarterectomy or stenting within 14 days. RESULTS: A total of 4719 CTAs were ordered during the 6-year period. There was nearly a tenfold rise in the yearly number of CTAs ordered per 10,000 ED visits, from 5.3 (in 2014) to 53.1 (in 2019). A total of 164 patients who underwent CTAs (3.5%) were ultimately transferred to a regional tertiary care centre, of whom 43 (0.9%) were transferred to a regional stroke centre for consideration of EVT. A total of 61 (1.3%) patients underwent a carotid intervention within 14 days. CONCLUSION: Little is known of the impacts on healthcare resources that have resulted from the system-wide changes made necessary by the widespread adoption of EVT. Our study shows that at our site, these system changes have resulted in large increases in CTA utilization with very small numbers of patients ultimately undergoing EVT or carotid intervention.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/terapia , Angiografia por Tomografia Computadorizada/métodos , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Resultado do Tratamento
5.
Epidemiol Prev ; 46(5-6): 367-375, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36628641

RESUMO

BACKGROUND: the reopening of Universities in a COVID-19 pandemic context represented a potential source of virus transmission among students. OBJECTIVES: to measure the SARS-CoV-2 real circulation among university students attending the University of Rome 'Niccolò Cusano' by seroprevalence analysis. DESIGN: retrospective study based on a point-of-care (POC) SARS-CoV-2 rapid qualitative serological screening performed on asymptomatic students attending the University. SETTING AND PARTICIPANTS: between September 2020 to July 2021 at Niccolò Cusano University, 9,588 SARS-CoV-2 lateral-flow rapid qualitative antibody assays were performed on a total of 2,423 asymptomatic students. Among them, 389 individuals with compulsory attendance were tested every 10 days for a minimum observational period of 7 months. MAIN OUTCOME MEASURES: the prevalence of SARS-CoV-2 IgM/IgG antibodies was estimated at more levels. It was calculated: 1. the number of positive cases detected among the total number of students tested during the screening period; 2. the cumulative seroprevalence over the time, and the seroprevalence distribution over the months; 3. the duration of seropositivity after SARS-CoV-2 infection in the known previous infected students repeatedly tested. RESULTS: a total of 112 participants had a SARS-CoV-2 positive IgG and/or IgM antibodies test, 39 of them with a documented history of previous infection. In the remaining 73 cases, 24 were confirmed with an external quantitative serological analysis and identified as individuals with unknown previous SARS-CoV-2 exposure, 17 resulted false positive and 32 subjects were excluded. The total seroprevalence was 2.6% (95%CI 2.0%-3.3%) and among the 63 confirmed seropositive cases, 75% had detectable IgG antibodies, 3% had IgM antibodies, and 22% were positive for both IgM and IgG antibodies. In the 389 repeatedly-tested students, 36 students were positive to SARS-CoV-2 antibodies, 14 with unknown previous infection, and 22 with known previous infection. Among these, 50% retained immune memory up to 4 months post infection and 27% of cases retained seropositivity up to 7 months. CONCLUSIONS: the data collected has been useful to measure a real epidemiological rate of the virus spread in a cohort of students in Italy as well as to obtain information on the antibodies seropositivity duration in individuals with previous infection.


Assuntos
COVID-19 , Pandemias , Humanos , Cidade de Roma/epidemiologia , Itália/epidemiologia , Estudos Retrospectivos , Estudos Soroepidemiológicos , COVID-19/epidemiologia , SARS-CoV-2 , Anticorpos Antivirais , Imunoglobulina G , Imunoglobulina M , Estudantes
6.
J Transl Med ; 19(1): 491, 2021 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-34861865

RESUMO

BACKGROUND: Nonthyroidal Illness Syndrome (NTIS) can be detected in many critical illnesses. Recently, we demonstrated that this condition is frequently observed in COVID-19 patients too and it is correlated with the severity the disease. However, the exact mechanism through which thyroid hormones influence the course of COVID-19, as well as that of many other critical illnesses, is not clear yet and treatment with T4, T3 or a combination of both is still controversial. Aim of this study was to analyze body composition in COVID-19 patients in search of possible correlation with the thyroid function. METHODS AND FINDINGS: We report here our experience performed in 74 critically ill COVID-19 patients hospitalized in the intensive care unit (ICU) of our University Hospital in Rome. In these patients, we evaluated the thyroid hormone function and body composition by Bioelectrical Impedance Analysis (BIA) during the acute phase of the disease at admission in the ICU. To examine the effects of thyroid function on BIA parameters we analyzed also 96 outpatients, affected by thyroid diseases in different functional conditions. We demonstrated that COVID-19 patients with low FT3 serum values exhibited increased values of the Total Body Water/Free Fat Mass (TBW/FFM) ratio. Patients with the lowest FT3 serum values had also the highest level of TBW/FFM ratio. This ratio is an indicator of the fraction of FFM as water and represents one of the best-known body-composition constants in mammals. We found an inverse correlation between FT3 serum values and this constant. Reduced FT3 serum values in COVID-19 patients were correlated with the increase in the total body water (TBW), the extracellular water (ECW) and the sodium/potassium exchangeable ratio (Nae:Ke), and with the reduction of the intracellular water (ICW). No specific correlation was observed in thyroid patients at different functional conditions between any BIA parameters and FT3 serum values, except for the patient with myxedema, that showed a picture similar to that seen in COVID-19 patients with NTIS. Since the Na+/K+ pump is a well-known T3 target, we measured the mRNA expression levels of the two genes coding for the two major isoforms of this pump. We demonstrated that COVID-19 patients with NTIS had lower levels of mRNA of both genes in the peripheral blood mononuclear cells (PBMC)s obtained from our patients during the acute phase of the disease. In addition, we retrieved data from transcriptome analysis, performed on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM)s treated with T3 and we demonstrated that in these cells T3 is able to stimulate the expression of these two genes in a dose-dependent manner. CONCLUSIONS: In conclusion, we demonstrated that measurement of BIA parameters is a useful method to analyze water and salt retention in COVID-19 patients hospitalized in ICU and, in particular, in those that develop NTIS. Our results indicate that NTIS has peculiar similarities with myxedema seen in severe hypothyroid patients, albeit it occurs more rapidly. The Na+/K+ pump is a possible target of T3 action, involved in the pathogenesis of the anasarcatic condition observed in our COVID-19 patients with NTIS. Finally, measurement of BIA parameters may represent good endpoints to evaluate the benefit of future clinical interventional trials, based on the administration of T3 in patients with NTIS.


Assuntos
COVID-19 , Leucócitos Mononucleares , Animais , Expressão Gênica , Humanos , SARS-CoV-2 , Sódio , Tri-Iodotironina
7.
PLoS One ; 16(11): e0260101, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34843537

RESUMO

OBJECTIVE: This study aimed to review the reasons why postpartum women present to the emergency department (ED) over a short term (≤10 days post-delivery) and to identify the risk factors associated with early visits to the ED. METHODS: This retrospective chart review included all women who delivered at a regional health system (William Osler Health System, WOHS) in 2018 and presented to the WOHS ED within 10 days after delivery. Baseline descriptive statistics were used to examine the patient demographics and identify the timing of the postpartum visit. Univariate tests were used to identify significant predictors for admission. A multivariate model was developed based on backward selection from these significant factors to identify admission predictors. RESULTS: There were 381 visits identified, and the average age of the patients was 31.22 years (SD: 4.83), with median gravidity of 2 (IQR: 1-3). Most patients delivered via spontaneous vaginal delivery (53.0%). The median time of presentation to the ED was 5.0 days, with the following most common reasons: abdominal pain (21.5%), wound-related issues (12.6%), and urinary issues (9.7%). Delivery during the weekend (OR 1.91, 95% CI 1.00-3.65, P = 0.05) was predictive of admission while Group B Streptococcus positive patients were less likely to be admitted (OR 0.22, CI 0.05-0.97, P<0.05). CONCLUSIONS: This was the first study in a busy community setting that examined ED visits over a short postpartum period. Patient education on pain management and wound care can reduce the rate of early postpartum ED visits.


Assuntos
Serviços Médicos de Emergência/tendências , Complicações do Trabalho de Parto/etiologia , Adulto , Canadá , Causalidade , Parto Obstétrico/tendências , Serviço Hospitalar de Emergência/tendências , Feminino , Número de Gestações , Hospitalização , Humanos , Complicações do Trabalho de Parto/epidemiologia , Manejo da Dor , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Período Pós-Parto , Gravidez , Fatores de Risco , Cicatrização
8.
Stem Cell Res ; 54: 102418, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34130155

RESUMO

In this study we describe the generation and characterization of an human induced pluripotent stem cell (hiPSC) line from a long QT syndrome type 1 (LQT1) patient carrying the KCNQ1 c.940 G > A (p.Gly314Ser) mutation. This patient-specific iPSC line has been obtained by using non-integrational Sendai reprogramming method, expresses pluripotency markers and has the capacity to differentiate into the three germ layers and into spontaneously beating cardiomyocytes (iPSC-CMs).


Assuntos
Células-Tronco Pluripotentes Induzidas , Síndrome de Romano-Ward , Linhagem Celular , Humanos , Canal de Potássio KCNQ1/genética , Mutação
9.
Clin Genet ; 100(3): 268-279, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33988253

RESUMO

Oculo-auriculo-vertebral spectrum (OAVS) is a developmental disorder of craniofacial morphogenesis. Its etiology is unclear, but assumed to be complex and heterogeneous, with contribution of both genetic and environmental factors. We assessed the occurrence of copy number variants (CNVs) in a cohort of 19 unrelated OAVS individuals with congenital heart defect. Chromosomal microarray analysis identified pathogenic CNVs in 2/19 (10.5%) individuals, and CNVs classified as variants of uncertain significance in 7/19 (36.9%) individuals. Remarkably, two subjects had small intragenic CNVs involving DACH1 and DACH2, two paralogs coding for key components of the PAX-SIX-EYA-DACH network, a transcriptional regulatory pathway controlling developmental processes relevant to OAVS and causally associated with syndromes characterized by craniofacial involvement. Moreover, a third patient showed a large duplication encompassing DMBX1/OTX3, encoding a transcriptional repressor of OTX2, another transcription factor functionally connected to the DACH-EYA-PAX network. Among the other relevant CNVs, a deletion encompassing HSD17B6, a gene connected with the retinoic acid signaling pathway, whose dysregulation has been implicated in craniofacial malformations, was also identified. Our findings suggest that CNVs affecting gene dosage likely contribute to the genetic heterogeneity of OAVS, and implicate the PAX-SIX-EYA-DACH network as novel pathway involved in the etiology of this developmental trait.


Assuntos
Variações do Número de Cópias de DNA , Síndrome de Goldenhar/genética , Cardiopatias Congênitas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Síndrome de Goldenhar/fisiopatologia , Humanos , Lactente , Recém-Nascido , Masculino , Análise em Microsséries , Polimorfismo de Nucleotídeo Único , Adulto Jovem
10.
Int J Mol Sci ; 22(3)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530447

RESUMO

Oculo-auriculo-vertebral-spectrum (OAVS; OMIM 164210) is a rare disorder originating from abnormal development of the first and second branchial arch. The clinical phenotype is extremely heterogeneous with ear anomalies, hemifacial microsomia, ocular defects, and vertebral malformations being the main features. MYT1, AMIGO2, and ZYG11B gene variants were reported in a few OAVS patients, but the etiology remains largely unknown. A multifactorial origin has been proposed, including the involvement of environmental and epigenetic mechanisms. To identify the epigenetic mechanisms contributing to OAVS, we evaluated the DNA-methylation profiles of 41 OAVS unrelated affected individuals by using a genome-wide microarray-based methylation approach. The analysis was first carried out comparing OAVS patients with controls at the group level. It revealed a moderate epigenetic variation in a large number of genes implicated in basic chromatin dynamics such as DNA packaging and protein-DNA organization. The alternative analysis in individual profiles based on the searching for Stochastic Epigenetic Variants (SEV) identified an increased number of SEVs in OAVS patients compared to controls. Although no recurrent deregulated enriched regions were found, isolated patients harboring suggestive epigenetic deregulations were identified. The recognition of a different DNA methylation pattern in the OAVS cohort and the identification of isolated patients with suggestive epigenetic variations provide consistent evidence for the contribution of epigenetic mechanisms to the etiology of this complex and heterogeneous disorder.


Assuntos
Metilação de DNA , Epigênese Genética , Estudo de Associação Genômica Ampla , Síndrome de Goldenhar/diagnóstico , Síndrome de Goldenhar/genética , Biologia Computacional/métodos , Ilhas de CpG , Feminino , Perfilação da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Anotação de Sequência Molecular , Fenótipo
11.
BMC Emerg Med ; 21(1): 10, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468044

RESUMO

BACKGROUND: A variety of evidence-based algorithms and decision rules using D-Dimer testing have been proposed as instruments to allow physicians to safely rule out a pulmonary embolism (PE) in low-risk patients. OBJECTIVE: To describe the prevalence of D-Dimer utilization among emergency department (ED) physicians and its impact on positive yields and utilization rates of Computed Tomography Pulmonary Angiography (CTPA). METHODS: Data was collected on all CTPA studies ordered by ED physicians at three sites during a 2-year period. Using a chi-square test, we compared the diagnostic yield for those patients who had a D-Dimer prior to their CTPA and those who did not. Secondary analysis was done to examine the impact of D-Dimer testing prior to CTPA on individual physician diagnostic yield or utilization rate. RESULTS: A total of 2811 CTPAs were included in the analysis. Of these, 964 CTPAs (34.3%) were ordered without a D-Dimer, and 343 (18.7%) underwent a CTPA despite a negative D-Dimer. Those CTPAs preceded by a D-Dimer showed no significant difference in positive yields when compared to those ordered without a D-Dimer (9.9% versus 11.3%, p = 0.26). At the individual physician level, no statistically significant relationship was found between D-Dimer utilization and CTPA utilization rate or diagnostic yield. CONCLUSION: This study provides evidence of suboptimal adherence to guidelines in terms of D-Dimer screening prior to CTPA, and forgoing CTPAs in patients with negative D-Dimers. However, the lack of a positive impact of D-Dimer testing on either CTPA diagnostic yield or utilization rate is indicative of issues relating to the high false-positive rates associated with D-Dimer screening.


Assuntos
Médicos , Embolia Pulmonar , Angiografia , Angiografia por Tomografia Computadorizada , Serviço Hospitalar de Emergência , Produtos de Degradação da Fibrina e do Fibrinogênio , Humanos , Embolia Pulmonar/diagnóstico por imagem , Estudos Retrospectivos
12.
Semin Cancer Biol ; 72: 27-35, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32259642

RESUMO

In the recent years the rapid scientific innovation in the evaluation of the individual's genome have allowed the identification of variants associated with the onset, treatment and prognosis of various pathologies including cancer, and with a potential impact in the assessment of therapy responses. Despite the analysis and interpretation of genomic information is considered incomplete, in many cases the identification of specific genomic profile has allowed the stratification of subgroups of patients characterized by a better response to drug therapies. Individual genome analysis has changed profoundly the diagnostic and therapeutic approach of breast cancer in the last 15 years by identifying selective molecular lesions that drive the development of neoplasms, showing that each tumor has its own genomic signature, with some specific features and some features common to several sub-types. Several personalized therapies have been (and still are being) developed showing a remarkable efficacy in the treatment of breast cancer.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Genômica , Mutação , Proteínas de Neoplasias/antagonistas & inibidores , Medicina de Precisão , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Feminino , Humanos , Proteínas de Neoplasias/genética , Prognóstico
13.
Clin Case Rep ; 8(12): 2333-2340, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33363735

RESUMO

This research resulted in the identification and submission of a novel RUNX2 gene mutation in the affected members of the studied pedigree. Mutation screening is an effective method for the early diagnosis of CCD in the affected individuals.

14.
Healthc Q ; 23(3): 48-53, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33243366

RESUMO

The Canadian Triage and Acuity Scale prioritizes patient care in the emergency department (ED) by setting recommendations for physician initial assessment (PIA) times. However, adherence to the recommended PIA times may not be possible due to increasing ED visits, overcrowding and patient boarding in the ED. We conducted a retrospective review of adult patients who visited four community EDs from January 2016 to December 2017 and found that the overall compliance with the recommended PIA times was low. This brings into question the utility of the current target PIA times and prompts the need for changes downstream to enable quicker patient assessments.


Assuntos
Benchmarking , Serviço Hospitalar de Emergência/normas , Triagem/normas , Adulto , Idoso , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ontário , Médicos/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo
15.
Clin Case Rep ; 8(8): 1445-1451, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884772

RESUMO

We characterize a large Italian family presenting with Marfan syndrome (MFS), where the same NM_000138.4:c.6872-1G > T splice site mutation in the FBN1 gene was detected in 37 affected individuals with different pathological phenotypes. Further studies on such a large pedigree could identify other genetic factors that influence MFS manifestation.

16.
Mech Ageing Dev ; 191: 111346, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32920077

RESUMO

Patients with connective tissue diseases (CTDs) are suspected to be at higher risk for cerebrovascular involvement, such as intracranial aneurysms, dissections and strokes, than the general population. Particularly, Marfan Syndrome (MFS) has been reported as associated with an increased risk of cerebrovascular alterations. Literature data report different prevalence of intracranial aneurysms in MFS, ranging from 4 % to 29 %, suggesting a role of genetic cause that involves the regulation of the TGF-ß signaling. Ischemic and hemorrhagic strokes have been also reported in MFS, but with an estimated prevalence from 3 % to 4 %. However, the aetiology of both events appears to be reliable more to a cardiac source than to the primary connective tissue defect. Finally, the available literature suggests that MFS patients have a higher prevalence of arterial tortuosity of neck and head vessels and these findings may be related to an enhanced chance of dissection. Overall, despite of the lack of studies, we could affirm that it may exists an increased prevalence of some neurovascular findings in MFS patients. Nevertheless, further studies are required to determine the true prevalence of these features and investigate specific gene mutations involved in MFS.


Assuntos
Acidente Vascular Cerebral Hemorrágico/metabolismo , Aneurisma Intracraniano/metabolismo , AVC Isquêmico/metabolismo , Síndrome de Marfan/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta , Artérias/anormalidades , Artérias/metabolismo , Artérias/patologia , Acidente Vascular Cerebral Hemorrágico/epidemiologia , Acidente Vascular Cerebral Hemorrágico/patologia , Humanos , Aneurisma Intracraniano/epidemiologia , AVC Isquêmico/epidemiologia , AVC Isquêmico/patologia , Instabilidade Articular/epidemiologia , Instabilidade Articular/metabolismo , Instabilidade Articular/patologia , Síndrome de Marfan/epidemiologia , Síndrome de Marfan/patologia , Prevalência , Dermatopatias Genéticas/epidemiologia , Dermatopatias Genéticas/metabolismo , Dermatopatias Genéticas/patologia , Malformações Vasculares/epidemiologia , Malformações Vasculares/metabolismo , Malformações Vasculares/patologia
17.
Clin Chim Acta ; 501: 154-164, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31730815

RESUMO

BACKGROUND: Marfan Syndrome (MFS) is a chronic, life-threatening, autosomal dominant connective tissue disorder caused by mutations in the FBN1 gene, coding for fibrillin-1. All organ systems may be affected, but particularly the cardiovascular system, eyes, and skeleton. Mortality generally results from cardiovascular complications, mainly aortic dissection. Currently, the diagnosis of MFS is based on the revised Ghent nosology. Molecular analysis of the FBN1 gene reduces diagnostic uncertainty in patients with suspected MFS or MFS-related disorders (MFS-RD). To date, more than 2700 FBN1 mutations are known. METHODS: Using Next Generation Sequencing (NGS) followed by Multiplex Ligation-dependent Probe Amplification on NGS-negative samples, we screened FBN1 gene on 124 unrelated patients (101 MFS fulfilling revised Ghent criteria, 20 suspected MFS, 3 MFS-RD) enrolled from 2008 to 2018 at the Multidisciplinary Marfan Clinic, Tor Vergata Hospital, Rome. RESULTS: An FBN1 variant was identified in 107/124 (86.3%) patients, including 48 novel variants (46 pathogenic/likely pathogenic, 2 VUS). A pathogenic/likely pathogenic variant was detected in 90/101 (89.1%) MFS patients. Our approach allowed early diagnosis for 10 young patients (age 3-19 years) with suspected MFS. CONCLUSIONS: This study broadens the mutation spectrum of FBN1, providing a full update of the molecular basis of MFS in Italy.


Assuntos
Análise Mutacional de DNA , Fibrilina-1/genética , Síndrome de Marfan/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
18.
Emerg Radiol ; 27(2): 127-134, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31754935

RESUMO

PURPOSE: To describe the inter-physician variability in the utilisation rate and diagnostic yield of computed tomography pulmonary angiography (CTPA) among a group of emergency department (ED) physicians working in a similar clinical environment. METHODS: We collected data on all CTPA studies ordered by ED physicians at three affiliated sites during a 2-year period between January 1, 2016, and December 31, 2017. For each physician, we calculated individual CTPA utilisation rate (total number of CTPAs ordered per 1000 ED visits) and diagnostic yield (percentage of CTPAs that were positive for PE). Additional analysis was carried out in order to identify the highest orderers of CTPA and their diagnostic yield. RESULTS: Seventy-seven ED physicians who collectively ordered a total of 2788 CTPAs were included in the study. Utilisation rates ranged from 1.1 to 22.2 CTPA per 1000 ED visits (median: 5.2 CTPA/1000 ED visits; 25%ile: 3.6 CTPA/1000 ED visits; 75%ile: 7.9 CTPA/1000 ED visits) and the CTPA diagnostic yields ranged from 0% to 33% (median: 9.1%; 25%ile: 5.2%; 75%ile: 16.1%). Those physicians in the lower quartile for ordering rate had a higher mean diagnostic yield when compared to the higher quartiles. CONCLUSION: The findings of this study demonstrate variability in CTPA ordering patterns and diagnostic yields among physicians working within the same clinical environment. There is some suggestion that those physicians who order disproportionately higher numbers of CTPAs have lower diagnostic yields.


Assuntos
Angiografia por Tomografia Computadorizada , Serviço Hospitalar de Emergência , Padrões de Prática Médica/estatística & dados numéricos , Embolia Pulmonar/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Triagem
19.
Mikrochim Acta ; 186(12): 798, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31734769

RESUMO

An imprinted electrochemical sensor was developed for the determination of the antibiotic oxacillin (OXC). A screen-printed carbon electrode (SPCE) was modified with gold nanourchin and graphene oxide, and then aniline was electro-polymerized in the presence of OXC to obtain a molecular imprint on the SPCE. The morphologies in sequential modification processes and the electrochemical behavior of the modified SCPE were characterized by field emission scanning electron microscopy and cyclic voltammetry. The performance of the sensor was evaluated by differential pulse voltammetry. At a typical peak potential of 0.82 mV (vs. Ag/AgCl), response is linear in the 0.7-575 nM OXC concentration range. The electrochemical sensitivity is 97.6 nA nM -1 cm -2, and the detection limit is 0.2 nM. The relative of replicate assays is 2.6% (for n = 6) at an OXC concentration level of 200 nM. The sensor is sensitive and selective. It was successfully applied for the detection of OXC in spiked cow's milk. Schematic presentation of electropolymerization of aniline on sreen-printed carbon electrode (SPCE) modified with graphene oxide (GO) and gold nanouchins (GNU) for voltammetric sensing of oxacillin.

20.
Healthc Q ; 21(4): 48-53, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30946655

RESUMO

The twin challenges of bed boarding and "hallway medicine" have emerged in recent years as key healthcare issues. Many hospitals, challenged with increasing demand and limited resources, have tried to find efficiencies within their operations. One such strategy is that of early morning discharges and expedited bed turnaround times. We conducted a retrospective study within three high-volume hospitals in the Greater Toronto Area looking at discharge times of in-patients and transfer times of admitted, Emergency Department (ED)-boarded patients. We discovered a consistent pattern of late-in-the-day discharges, and even later-in-the-day transfers of boarded ED patients, indicating that this may be a potential source of increased efficiency for overburdened hospitals.


Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Comunitários/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Ocupação de Leitos , Aglomeração , Humanos , Ontário , Admissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo
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