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OBJECTIVE: Arterial-phase artifacts are gadoxetic acid (GA)-enhanced MRI's major drawback, ranging from 5 to 39%. We evaluate the effect of dilution and slow injection of GA using automated fluoroscopic triggering on liver MRI arterial-phase (AP) acquisition timing, artifact frequency, and lesion visibility. METHODS AND MATERIALS: Saline-diluted 1:1 GA was injected at 1 ml/s into 1413 patients for 3 T liver MRI. Initially, one senior abdominal radiologist, i.e., principal investigator (PI), assessed all MR exams and compared them to previous and follow-up images, as well as the radiology report on record, determining the standard of reference for lesion detection and characterization. Then, three other readers independently evaluated the AP images for artifact type (truncation (TA), transient severe motion (TSM) or mixed), artifact severity (on a 5-point scale), acquisition timing (on a 4-point scale) and visibility (on a 5-point scale) of hypervascular lesions ≥ 5 mm, selected by the PI. Artifact score ≥ 4 and artifact score ≤ 3 were considered significant and non-significant artifacts, respectively. RESULTS: Of the 1413 exams, diagnostic-quality arterial-phase images included 1100 (77.8%) without artifacts, 220 (15.6%) with minimal, and 77 (5.4%) with moderate artifacts. Only 16 exams (1.1%) had significant artifacts, 13 (0.9%) with severe artifacts (score 4), and three (0.2%) non-diagnostic artifacts (score 5). AP acquisition timing was optimal in 1369 (96.8%) exams. Of the 449 AP hypervascular lesions, 432 (96.2%) were detected. CONCLUSION: Combined dilution and slow injection of GA with MR results in well-timed arterial-phase images in 96.8% and a reduction of exams with significant artifacts to 1.1%. CLINICAL RELEVANCE STATEMENT: Hypervascular lesions, in particular HCC detection, hinge on arterial-phase hyperenhancement, making well-timed, artifact-free arterial-phase images a prerequisite for accurate diagnosis. Saline dilution 1:1, slow injection (1 ml/s), and automated bolus triggering reduce artifacts and optimize acquisition timing. KEY POINTS: ⢠There was substantial agreement among the three readers regarding the presence and type of arterial-phase (AP) artifacts, acquisition timing, and lesion visibility. ⢠Impaired AP hypervascular lesion visibility occurred in 17 (3.8%) cases; in eight lesions due to mistiming and in nine lesions due to significant artifacts. ⢠When AP timing was suboptimal, it was too late in 40 exams (3%) and too early in 4 exams (0.2%) of exams.
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Artefatos , Meios de Contraste , Gadolínio DTPA , Imageamento por Ressonância Magnética , Humanos , Meios de Contraste/administração & dosagem , Feminino , Masculino , Gadolínio DTPA/administração & dosagem , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Idoso , Adulto , Idoso de 80 Anos ou mais , Estudos de Coortes , Neoplasias Hepáticas/diagnóstico por imagem , Aumento da Imagem/métodos , Adulto Jovem , Fígado/diagnóstico por imagemRESUMO
OBJECTIVES: Our aim was twofold. First, to validate Anali scores with and without gadolinium (ANALIGd and ANALINoGd) in primary sclerosing cholangitis (PSC) patients. Second, to compare the ANALIs prognostic ability with the recently-proposed potential functional stricture (PFS). MATERIALS AND METHODS: This retrospective study included 123 patients with a mean age of 41.5 years, who underwent gadoxetic acid-enahnced MRI (GA-MRI). Five readers independently evaluated all images for calculation of ANALIGd and ANALINoGd scores based upon following criteria: intrahepatic bile duct change severity, hepatic dysmorphia, liver parenchymal heterogeneity, and portal hypertension. In addition, hepatobiliary contrast excretion into first-order bile ducts was evaluated on 20-minute hepatobiliary-phase (HBP) images to assess PFS. Inter- and intrareader agreement were calculated (Fleiss´and Cohen kappas). Kaplan-Meier curves were generated for survival analysis. ANALINoGd, ANALIGd, and PFS were correlated with clinical scores, labs and outcomes (Cox regression analysis). RESULTS: Inter-reader agreement was almost perfect (Ï° = 0.81) for PFS, but only moderate-(Ï° = 0.55) for binary ANALINoGd. For binary ANALIGd, the agreement was slightly better on HBP (Ï° = 0.64) than on arterial-phase (AP) (Ï° = 0.53). Univariate Cox regression showed that outcomes for decompensated cirrhosis, orthotopic liver transplantation or death significantly correlated with PFS (HR (hazard ratio) = 3.15, p < 0.001), ANALINoGd (HR = 6.42, p < 0.001), ANALIGdHBP (HR = 3.66, p < 0.001) and ANALIGdAP (HR = 3.79, p < 0.001). Multivariate analysis identified the PFS, all three ANALI scores, and Revised Mayo Risk Score as independent risk factors for outcomes (HR 3.12, p < 0.001; 6.12, p < 0.001; 3.56, p < 0.001;3.59, p < 0.001; and 4.13, p < 0.001, respectively). CONCLUSION: ANALINoGd and GA-MRI-derived ANALI scores and PFS could noninvasively predict outcomes in PSC patients. CLINICAL RELEVANCE STATEMENT: The combined use of Anali scores and the potential functional stricture (PFS), both derived from unenhanced-, and gadoxetic acid enhanced-MRI, could be applied as a diagnostic and prognostic imaging surrogate for counselling and monitoring primary sclerosing cholangitis patients. KEY POINTS: Primary sclerosing cholangitis patients require radiological monitoring to assess disease stability and for the presence and type of complications. A contrast-enhanced MRI algorithm based on potential functional stricture and ANALI scores risk-stratified these patients. Unenhanced ANALI score had a high negative predictive value, indicating some primary sclerosing cholangitis patients can undergo non-contrast MRI surveillance.
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Nationwide, an estimated 500,000 to 1 million people are not insured and therefore lack access to regular health structures, which can have fatal consequences for the health of those affected. Especially in large cities, there are low-threshold medical outpatient clinics that offer basic health care parallel to the regular system. Sustainable solutions for ensuring adequate healthcare are lacking. Clearing centers (German: Clearingstelle), serving as contact points for people without health insurance coverage, and the concept of an Anonymous Treatment Voucher (German: Anonymer Behandlungsschein; ABS), bridge the gap between parallel and regular health systems. With the pilot implementation of "Clearing Center 1.0" at the Public Health Authority in Frankfurt am Main from 2020 to 2022, the basic medical care of Humanitarian Consultation Hour was complemented by professional social counseling with the aim of referring as many individuals as possible to the statutory regular system. The expansion of the counseling services and the permanent establishment of the clearing center in Frankfurt am Main are declared goals for the Public Health Authority.
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Acessibilidade aos Serviços de Saúde , Alemanha , Programas Nacionais de Saúde , Cobertura do Seguro/estatística & dados numéricos , Humanos , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Modelos OrganizacionaisRESUMO
OBJECTIVES: To investigate the effect of saline-diluted gadoxetic acid, done for arterial-phase (AP) artifact reduction, on signal intensity (SI), and hence focal lesion conspicuity on MR imaging. METHODS: We retrospectively examined 112 patients who each had at least two serial gadoxetic acid-enhanced liver MRIs performed at 1 ml/s, first with non-diluted (ND), then with 1:1 saline-diluted (D) contrast. Two blinded readers independently analyzed the artifacts and graded dynamic images using a 5-point scale. The absolute SI of liver parenchyma, focal liver lesions (if present), aorta, and portal vein at the level of the celiac trunk and the SI of the paraspinal muscle were measured in all phases. The signal-to-norm (SINorm) of the vascular structures, hepatic parenchyma and focal lesions, and the contrast-to-norm (CNorm) of focal liver lesions were calculated. RESULTS: AP artifacts were significantly reduced with dilution. Mean absolute contrast-enhanced liver SI was significantly higher on the D exams compared to the ND exams. Likewise, SINorm of liver parenchyma was significantly higher in all contrast-enhanced phases except transitional phase on the D exams. SINorm values in the AP for the aorta and in the PVP for portal vein were significantly higher on the diluted exams. The CNorm was not significantly different between ND and D exams for lesions in any imaging phase. The interclass correlation coefficient was excellent (0.89). CONCLUSION: Gadoxetic acid dilution injected at 1ml/s produces images with significantly fewer AP artifacts but no significant loss in SINorm or CNorm compared to standard non-diluted images. KEY POINTS: ⢠Diluted gadoxetic acid at slow injection (1 ml/s) yielded images with higher SINorm of the liver parenchyma and preserved CNorm for focal liver lesions. ⢠Gadoxetic acid-enhanced MRI injected at 1 ml/s is associated with arterial-phase (AP) artifacts in 31% of exams, which may degrade image quality and limits focal liver lesion detection. ⢠Saline dilution of gadoxetic acid 1:1 combined with a slow injection rate of 1 ml/s significantly reduced AP artifacts from 31 to 9% and non-diagnostic AP artifacts from 16 to 1%.
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Artefatos , Neoplasias Hepáticas , Humanos , Estudos Retrospectivos , Meios de Contraste/farmacologia , Gadolínio DTPA/farmacologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Hepáticas/patologia , Artéria Hepática/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Solução SalinaRESUMO
OBJECTIVE: To compare unsupervised deep clustering (UDC) to fat fraction (FF) and relative liver enhancement (RLE) on Gd-EOB-DTPA-enhanced MRI to distinguish simple steatosis from non-alcoholic steatohepatitis (NASH), using histology as the gold standard. MATERIALS AND METHODS: A derivation group of 46 non-alcoholic fatty liver disease (NAFLD) patients underwent 3-T MRI. Histology assessed steatosis, inflammation, ballooning, and fibrosis. UDC was trained to group different texture patterns from MR data into 10 distinct clusters per sequence on unenhanced T1- and Gd-EOB-DTPA-enhanced T1-weighted hepatobiliary phase (T1-Gd-EOB-DTPA-HBP), then on T1 in- and opposed-phase images. RLE and FF were quantified on identical sequences. Differences of these parameters between NASH and simple steatosis were evaluated with χ2- and t-tests, respectively. Linear regression and Random Forest classifier were performed to identify associations between histological NAFLD features, RLE, FF, and UDC patterns, and then determine predictors able to distinguish simple steatosis from NASH. ROC curves assessed diagnostic performance of UDC, RLE, and FF. Finally, we tested these parameters on 30 validation cohorts. RESULTS: For the derivation group, UDC-derived features from unenhanced and T1-Gd-EOB-DTPA-HBP, plus from T1 in- and opposed-phase, distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.02, respectively) with 85% and 80% accuracy, respectively, while RLE and FF distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.004, respectively), with 83% and 78% accuracy, respectively. On multivariate regression analysis, RLE and FF correlated only with fibrosis (p = 0.040) and steatosis (p ≤ 0.001), respectively. Conversely, UDC features, using Random Forest classifier predictors, correlated with all histologic NAFLD components. The validation group confirmed these results for both approaches. CONCLUSION: UDC, RLE, and FF could independently separate NASH from simple steatosis. UDC may predict all histologic NAFLD components. CLINICAL RELEVANCE STATEMENT: Using gadoxetic acid-enhanced MR, fat fraction (FF > 5%) can diagnose NAFLD, and relative liver enhancement can distinguish NASH from simple steatosis. Adding AI may let us non-invasively estimate the histologic components, i.e., fat, ballooning, inflammation, and fibrosis, the latter the main prognosticator. KEY POINTS: ⢠Unsupervised deep clustering (UDC) and MR-based parameters (FF and RLE) could independently distinguish simple steatosis from NASH in the derivation group. ⢠On multivariate analysis, RLE could predict only fibrosis, and FF could predict only steatosis; however, UDC could predict all histologic NAFLD components in the derivation group. ⢠The validation cohort confirmed the findings for the derivation group.
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Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/patologia , Inteligência Artificial , Meios de Contraste/farmacologia , Gadolínio DTPA , Fígado/diagnóstico por imagem , Fígado/patologia , Imageamento por Ressonância Magnética/métodos , Inflamação/patologia , FibroseRESUMO
OBJECTIVES: PSC strictures are routinely diagnosed on T2-MRCP as dominant- (DS) or high-grade stricture (HGS). However, high inter-observer variability limits their utility. We introduce the "potential functional stricture" (PFS) on T1-weighted hepatobiliary-phase images of gadoxetic acid-enhanced MR cholangiography (T1-MRC) to assess inter-reader agreement on diagnosis, location, and prognostic value of PFS on T1-MRC vs. DS or HGS on T2-MRCP in PSC patients, using ERCP as the gold standard. METHODS: Six blinded readers independently reviewed 129 MRIs to diagnose and locate stricture, if present. DS/HGS was determined on T2-MRCP. On T1-MRC, PFS was diagnosed if no GA excretion was seen in the CBD, hilum or distal RHD, or LHD. If excretion was normal, "no functional stricture" (NFS) was diagnosed. T1-MRC diagnoses (NFS = 87; PFS = 42) were correlated with ERCP, clinical scores, labs, splenic volume, and clinical events. Statistical analyses included Kaplan-Meier curves and Cox regression. RESULTS: Interobserver agreement was almost perfect for NFS vs. PFS diagnosis, but fair to moderate for DS and HGS. Forty-four ERCPs in 129 patients (34.1%) were performed, 39 in PFS (92.9%), and, due to clinical suspicion, five in NFS (5.7%) patients. PFS and NFS diagnoses had 100% PPV and 100% NPV, respectively. Labs and clinical scores were significantly worse for PFS vs. NFS. PFS patients underwent more diagnostic and therapeutic ERCPs, experienced more clinical events, and reached significantly more endpoints (p < 0.001) than those with NFS. Multivariate analysis identified PFS as an independent risk factor for liver-related events. CONCLUSION: T1-MRC was superior to T2-MRCP for stricture diagnosis, stricture location, and prognostication. CLINICAL RELEVANCE STATEMENT: Because half of PSC patients will develop clinically-relevant strictures over the course of the disease, earlier more confident diagnosis and correct localization of functional stricture on gadoxetic acid-enhanced MRI may optimize management and improve prognostication. KEY POINTS: ⢠There is no consensus regarding biliary stricture imaging features in PSC that have clinical relevance. ⢠Twenty-minute T1-weighted MRC images correctly classified PSC patients with potential (PFS) vs with no functional stricture (NFS). ⢠T1-MRC diagnoses may reduce the burden of diagnostic ERCPs.
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Colangiopancreatografia por Ressonância Magnética , Colangite Esclerosante , Humanos , Colangiopancreatografia por Ressonância Magnética/métodos , Constrição Patológica , Colangite Esclerosante/complicações , Colangite Esclerosante/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Colangiopancreatografia Retrógrada EndoscópicaRESUMO
BACKGROUND & AIMS: Functional liver imaging score (FLIS) - derived from gadoxetic acid-enhanced MRI - correlates with liver function and independently predicts liver-related mortality in patients with chronic liver disease (CLD), while splenic craniocaudal diameter (SCCD) is a marker of portal hypertension. The aim of this study was to investigate the accuracy of a combination of FLIS and SCCD for predicting hepatic decompensation, acute-on-chronic liver failure (ACLF), and mortality in patients with advanced CLD (ACLD). METHODS: We included 397 patients with CLD who underwent gadoxetic acid-enhanced liver MRI. The FLIS was calculated by summing the points (0-2) of 3 hepatobiliary-phase features: hepatic enhancement, biliary excretion, and portal vein signal intensity. Patients were stratified into 3 groups according to liver fibrosis severity and presence/history of hepatic decompensation: non-ACLD, compensated ACLD (cACLD), and decompensated ACLD (dACLD). RESULTS: SCCD showed excellent intra- and inter-reader agreement. Importantly, SCCD was an independent risk factor for hepatic decompensation in patients with cACLD (per cm; adjusted hazard ratio [aHR] 1.13; 95% CI 1.04-1.23; p = 0.004). Patients with cACLD and a FLIS of 0-3 points and/or a SCCD of >13 cm were at increased risk of hepatic decompensation (aHR 3.07; 95% CI 1.43-6.59; p = 0.004). In patients with dACLD, a FLIS of 0-3 was independently associated with an increased risk of ACLF (aHR 2.81; 95% CI 1.16-6.84; p = 0.02), even after adjusting for other prognostic factors. Finally, a FLIS and SCCD-based algorithm was independently predictive of transplant-free mortality and stratified the probability of transplant-free survival (TFS) in ACLD (p <0.001): FLIS 4-6 and SCCD ≤13 cm (5-year TFS of 84%) vs. FLIS 4-6 and SCCD >13 cm (5-year TFS of 70%) vs. FLIS 0-3 (5-year TFS of 24%). CONCLUSION: The FLIS and SCCD are simple imaging markers that provide complementary information for risk stratification in patients with compensated and decompensated ACLD. LAY SUMMARY: Magnetic resonance imaging (MRI) can be used to assess the state of the liver. Previously the functional liver imaging score, which is based on MRI criteria, was developed as a measure of liver function and to predict the risk of liver-related complications or death. By combining this score with a measurement of spleen diameter, also using MRI, we generated an algorithm that could predict the risk of adverse liver-related outcomes in patients with advanced chronic liver disease.
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Insuficiência Hepática Crônica Agudizada , Hipertensão Portal , Neoplasias Hepáticas , Insuficiência Hepática Crônica Agudizada/complicações , Meios de Contraste , Gadolínio DTPA , Humanos , Hipertensão Portal/complicações , Hipertensão Portal/diagnóstico por imagem , Fígado/diagnóstico por imagem , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Neoplasias Hepáticas/complicações , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Baço/diagnóstico por imagemRESUMO
OBJECTIVES: T2 mapping of the liver is a potential diagnostic tool, but conventional techniques are difficult to perform in clinical practice due to long scan time. We aimed to evaluate the accuracy of a prototype radial turbo-spin-echo (rTSE) sequence, optimized for multi-slice T2 mapping in the abdomen during one breath-hold at 3 T. METHODS: A multi-sample (fat: 0-35%) agarose phantom doped with MnCl2 and 80 subjects (73 patients undergoing abdomen MR examination and 7 healthy volunteers) were investigated. A radial turbo-spin-echo (rTSE) sequence with and without fat suppression, a Cartesian turbo-spin-echo (Cart-TSE) sequence, and a single-voxel multi-echo STEAM spectroscopy (HISTO) were performed in phantom, and fat-suppressed rTSE and HISTO sequences were performed in in vivo measurements. Two approaches were used to sample T2 values: manually selected circular ROIs and whole liver analysis with Gaussian mixture models (GMM). RESULTS: The rTSE-T2s values exhibited a strong correlation with Cart-TSE-T2s (R2 = 0.988) and with HISTO-T2s of water (R2 = 0.972) in phantom with an offset between rTSE and Cart-TSE maps (mean difference = 3.17 ± 1.18 ms). The application of fat suppression decreased T2 values, and the effect was directly proportional to the amount of fat. Measurements in patients yielded a linear relationship between rTSE- and HISTO-T2s (R2 = 0.546 and R2 = 0.580 for ROI and GMM, respectively). CONCLUSION: The fat-suppressed rTSE sequence allows for fast and accurate determination of T2 values of the liver, and appears to be suitable for further large cohort studies. KEY POINTS: â¢Radial turbo-spin-echo T2 mapping performs comparably to Cartesian TSE-T2 mapping, but an offset in values is observed in phantom measurements. â¢Fat-suppressed radial turbo-spin-echo T2 mapping is consistent with T2 of water as assessed by MRS in phantom measurements. â¢Fat-suppressed radial turbo-spin-echo sequence allows fast T2 mapping of the liver in a single breath-hold and is correlated with MRS-based T2 of water.
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Suspensão da Respiração , Imageamento por Ressonância Magnética , Abdome , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , ÁguaRESUMO
Transgenerational immune priming is the process of increased resistance to infection in offspring due to parental pathogen exposure. Honey bees (Apis mellifera L. (Hymenoptera: Apidae)) are hosts to multiple pathogens, and this complex immune function could help protect against overwhelming infection. Honey bees have demonstrated transgenerational immune priming for the bacterial pathogen Paenibacillus larvae; however, evidence for viral transgenerational immune priming is lacking across insects in general. Here we test for the presence of transgenerational immune priming in honey bees with Deformed wing virus (DWV) by injecting pupae from DWV-exposed queens and measuring virus titer and immune gene expression. Our data suggest that there is evidence for viral transgenerational immune priming in honey bees, but it is highly context-dependent based on route of maternal exposure and potentially host genetics or epigenetic factors.
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Abelhas , Vírus de Insetos , Vírus de RNA , Animais , Abelhas/imunologia , Abelhas/virologia , Feminino , Exposição Materna , Pupa , Carga ViralRESUMO
This study examined the direct and indirect associations of teachers' depressive symptoms with children's math achievement through teachers' reports of family-teacher relationships and children's approaches to learning (ATL) in Head Start. This study included 3- and 4-year-old 1,547 children (49% female; 27% White, 24% Black, 41% Hispanic/Latino, and 8% others) who attended Head Start from fall 2014 through spring 2015. Results indicated that teachers' depressive symptoms were directly associated with lower gains in children's math skills over a year. In addition, teachers who reported higher depressive symptoms were less likely to report positive family-teacher relationships. This, in turn, resulted in lower gains in children's ATL and was associated with lower achievement in math skills (r2 = .69).
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Logro , Depressão , Criança , Pré-Escolar , Feminino , Humanos , Aprendizagem , Masculino , Matemática , Professores EscolaresRESUMO
Background Gadoxetic acid-enhanced MRI enables estimation of liver function in patients with chronic liver disease (CLD). The functional liver imaging score (FLIS), derived from gadoxetic acid-enhanced MRI, has been shown to predict transplant-free survival in liver transplant patients. Purpose To investigate the accuracy of the FLIS for predicting hepatic decompensation and transplant-free survival in patients with CLD. Materials and Methods Patients with CLD who had undergone gadoxetic acid-enhanced liver MRI, including T1-weighted volume-interpolated breath-hold examination sequences with fat suppression, performed between 2011 and 2015 were included. FLIS was assigned on the basis of the sum of three hepatobiliary phase features, each scored on an ordinal 0-2 scale: hepatic enhancement, biliary excretion, and the signal intensity in the portal vein. Patients were stratified into the following three groups according to fibrosis stage and a presence or history of hepatic decompensation: nonadvanced CLD, compensated advanced CLD (CACLD), and decompensated advanced CLD (DACLD). The predictive value of FLIS for first and/or further hepatic decompensation and for transplant-free survival was investigated by using Kaplan-Meier analysis, log-rank tests, and Cox regression analysis. Results This study evaluated 265 patients (53 years ± 14 [standard deviation]; 164 men). Intraobserver (κ = 0.98; 95% confidence interval: 0.97, 0.99) and interobserver (κ = 0.93; 95% confidence interval: 0.90, 0.95) agreement for FLIS were excellent. In patients with CACLD, the FLIS was independently predictive of a first hepatic decompensation (adjusted hazard ratio, 3.7; 95% confidence interval: 1.1, 12.6; P = .04), but not for further hepatic decompensations in patients with DACLD (adjusted hazard ratio, 1.4; 95% confidence interval: 0.9, 1.9; P = .17). The FLIS was an independent risk factor for mortality in both patients with CACLD (adjusted hazard ratio, 7.4; 95% confidence interval: 2.7, 20.2; P < .001) and those with DACLD (adjusted hazard ratio, 3.8; 95% confidence interval: 1.7, 9.5; P = .004). Conclusion The functional liver imaging score derived from gadoxetic acid-enhanced MRI identified patients with advanced chronic liver disease who are at increased risk for a first hepatic decompensation and for mortality. © RSNA, 2019 Online supplemental material is available for this article.
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Meios de Contraste , Gadolínio DTPA , Aumento da Imagem/métodos , Hepatopatias/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Doença Crônica , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: To explore whether sarcopenia, diagnosed by an abbreviated magnetic resonance imaging (MRI) protocol is a risk factor for hepatic decompensation and mortality in patients with chronic liver disease (CLD). METHODS: In this retrospective single-centre study we included 265 patients (164 men, mean age 54 ± 16 years) with CLD who had undergone MRI of the liver between 2010 and 2015. Transverse psoas muscle thickness (TPMT) was measured on unenhanced and contrast-enhanced T1-weighted and T2-weighted axial images. Sarcopenia was defined by height-adjusted and gender-specific cut-offs in women as TPMT < 8 mm/m and in men as TPMT < 12 mm/m respectively. Patients were further stratified into three prognostic stages according to the absence of advanced fibrosis (FIB-4 < 1.45, non-advanced CLD), compensated-advanced CLD (cACLD) and decompensated-advanced CLD (dACLD). RESULTS: The inter-observer agreement for the TPMT measurements (κ = 0.98; 95% confidence interval [95% CI]:0.96-0.98), as well as the intra-observer agreement between the three image sequences (κ = 0.99; 95% CI: 0.99-1.00) were excellent. Sarcopenia was not predictive of first or further hepatic decompensation. In patients with cACLD and dACLD, sarcopenia was a risk factor for mortality (cACLD: hazard ratio (HR):3.13, 95% CI: 1.33-7.41, P = .009; dACLD:HR:2.45, 95% CI: 1.32-4.57, P = .005) on univariate analysis. After adjusting for the model of end-stage liver disease (MELD) score, albumin and evidence of clinical significant portal hypertension, sarcopenia (adjusted HR: 2.76, 95% CI: 1.02-7.42, P = .045) remained an independent risk factor for mortality in patients with cACLD. CONCLUSION: Sarcopenia can be easily evaluated by a short MRI exam without the need for contrast injection. Sarcopenia is a risk factor for mortality, especially in patients with cACLD.
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Sarcopenia , Adulto , Idoso , Feminino , Humanos , Cirrose Hepática/complicações , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculos Psoas , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagemRESUMO
Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems. Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. Exposures: Ultra-rapid exome sequencing. Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%). Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.
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Estado Terminal , Sequenciamento do Exoma/métodos , Doenças Genéticas Inatas/genética , Testes Genéticos/métodos , Austrália , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Doenças Genéticas Inatas/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Programas Nacionais de Saúde , Estudos Prospectivos , Fatores de TempoRESUMO
PURPOSE: To identify independent imaging features and establish a diagnostic algorithm for diagnosis of cystic fibrosis (CF)-associated liver disease (CFLD) in CF patients compared to controls using gadoxetic acid-enhanced MRI. METHODS: A total of 90 adult patients were enrolled: 50 with CF, 40 controls. The CF group was composed of two subgroups: a retrospective test subgroup (n = 33) and a prospective validation subgroup (n = 17). Controls (patients with normal liver enzymes and only benign focal liver lesions) were divided accordingly (27:13). MRI variables, including quantitative and qualitative parameters, were used to distinguish CFLD from controls using clinical symptoms, laboratory tests and Debray criteria. Disease severity was classified according to Child-Pugh and Albumin-Bilirubin (ALBI) scores. Fifteen qualitative single-lesion CF descriptors were defined. Two readers independently evaluated the images. Univariate statistical analysis was performed to obtain significant imaging features that differentiate CF patients from controls. Through multivariate analysis using chi-squared automatic interaction detector (CHAID) methodology the most important descriptors were identified. Diagnostic performance was assessed by receiver-operating characteristic (ROC) analysis. RESULTS: Three independent imaging descriptors distinguished CFLD from controls: (1) presence of altered gallbladder morphology; (2) periportal tracking; and (3) periportal fat deposition. Prospective validation of the classification algorithm demonstrated a sensitivity of 94.1% and specificity of 84.6% for discriminating CFLD from controls. Disease severity was well associated with the imaging features. CONCLUSIONS: A short unenhanced MRI protocol can identify the three cardinal imaging features of CFLD. The hepatobiliary phase of gadoxetic acid-enhanced MRI can define CFLD progression. KEY POINTS: ⢠Using a multivariate classification analysis, we identified three independent imaging features, altered gallbladder morphology (GBAM), periportal tracking (PPT) and periportal fat deposition (PPFD), that could diagnose CFLD with high sensitivity, 94.1 % (95% CI: 71.3-99.9) and moderate specificity, 84.6 % (95% CI: 54.6-98.1). ⢠Based upon the results of this study, gadoxetic acid-enhanced MRI with DWI is able to diagnose early-stage CFLD, as well as its progression.
Assuntos
Fibrose Cística/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Adulto , Algoritmos , Estudos de Coortes , Fibrose Cística/complicações , Feminino , Gadolínio DTPA , Humanos , Hepatopatias/etiologia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVES: To examine inter- and intra-observer agreement for four simple hepatobiliary phase (HBP)-based scores on gadoxetic acid (GA)-enhanced MRI and their correlation with liver function in patients with mixed chronic liver disease (CLD). METHODS: This single-center, retrospective study included 287 patients (62% male, 38% female, mean age 53.5 ± 13.7 years) with mixed CLD (20.9% hepatitis C, 19.2% alcoholic liver disease, 8% hepatitis B) who underwent GA-enhanced MRI of the liver for clinical care between 2010 and 2015. Relative liver enhancement (RLE), contrast uptake index (CUI), hepatic uptake index (HUI), and liver-to-spleen contrast index (LSI) were calculated by two radiologists independently using unenhanced and GA-enhanced HPB (obtained 20 min after GA administration) images; 50 patients selected at random were reviewed twice by one reader to assess intra-observer reliability. Agreement was assessed by intraclass correlation coefficient (ICC). The albumin-bilirubin (ALBI) score, the model of end-stage liver disease (MELD), and the Child-Turcotte-Pugh (CTP) score were calculated as standards of reference for hepatic function. RESULTS: Intra-observer ICCs ranged from 0.814 (0.668-0.896) for CUI to 0.969 (0.945-0.983) for RLE. Inter-observer ICCs ranged from 0.777 (0.605-0.874) for HUI to 0.979 (0.963-0.988) for RLE. All HBP-based scores correlated significantly (all p < 0.001) with the ALBI, MELD, and CTP scores and were able to discriminate patients with a MELD score ≥ 15 versus ≤ 14, with area under the curve values ranging from 0.760 for RLE to 0.782 for HUI. CONCLUSION: GA-enhanced, MRI-derived, HBP-based parameters showed excellent inter- and intra-observer agreement. All HBP-based parameters correlated with clinical and laboratory scores of hepatic dysfunction, with no significant differences between each other. KEY POINTS: ⢠Radiological parameters that quantify the hepatic uptake of gadoxetic acid are highly reproducible. ⢠These parameters can be used interchangeably because they correlate with each other and with scores of hepatic dysfunction. ⢠Assessment of these parameters may be helpful in monitoring disease progression.
Assuntos
Gadolínio DTPA/farmacologia , Hepatopatias/diagnóstico , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Meios de Contraste/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Adulto JovemRESUMO
Increased protein kinase C (PKC) activity is associated with heart failure, and can target multiple cardiac troponin I (cTnI) residues in myocytes, including S23/24, S43/45 and T144. In earlier studies, cTnI-S43D and/or -S45D augmented S23/24 and T144 phosphorylation, which suggested there is communication between clusters. This communication is now explored by evaluating the impact of phospho-mimetic cTnI S43/45D combined with S23/24D (cTnIS4D) or T144D (cTnISDTD). Gene transfer of epitope-tagged cTnIS4D and cTnISDTD into adult cardiac myocytes progressively replaced endogenous cTnI. Partial replacement with cTnISDTD or cTnIS4D accelerated the time to peak (TTP) shortening and time to 50% re-lengthening (TTR50%) on day 2, but peak shortening was only diminished by cTnIS4D. Extensive cTnIS4D replacement continued to accelerate TTP, and decrease shortening amplitude, while TTR50% returned to baseline levels on day 4. In contrast, cTnISDTD modestly reduced shortening amplitude and continued to accelerate myocyte TTP and TTR50%. These results indicate cTnIS43/45 communicates with S23/24 and T144, with S23/24 exacerbating and T144 attenuating the S43/45D-dependent functional deficit. In addition, more severe functional alterations in cTnIS4D myocytes were accompanied by higher levels of secondary phosphorylation compared to cTnISDTD. These results suggest that secondary phosphorylation helps to maintain steady-state contractile function during chronic cTnI phosphorylation at PKC sites.
Assuntos
Miócitos Cardíacos/citologia , Proteína Quinase C/metabolismo , Troponina I/metabolismo , Animais , Células Cultivadas , Contração Miocárdica , Miócitos Cardíacos/metabolismo , Fosforilação , Ratos , Sarcômeros/metabolismoRESUMO
OBJECTIVES: The aim of the study was to evaluate efficacy of nutrition and physical activity interventions in the clinical management of paediatric nonalcoholic fatty liver disease. The prevalence of paediatric nonalcoholic fatty liver disease continues to rise alongside childhood obesity. Weight loss through lifestyle modification is currently first-line treatment, although supplementation of specific dietary components may be beneficial. METHODS: Medline, CINAHL, EMBASE, Scopus, and Cochrane Libraries were systematically searched to identify randomized controlled trials assessing nutritional and physical activity interventions. Primary outcome measures were changes to liver biomarkers assessed by imaging, histology, or serum liver function tests. Study quality was evaluated using the American Dietetic Association Quality Criteria Checklist. RESULTS: Fifteen articles met eligibility criteria investigating nutritional supplementation (vitamin E [nâ=â6], probiotics [nâ=â2], omega-3 fatty acids [nâ=â5]), dietary modification (low glycaemic load [nâ=â1] and reducing fructose intake [nâ=â1]). No randomized controlled trials examining physical activity interventions were identified. Vitamin E was ineffective at improving alanine transaminase levels, whereas omega-3 fatty acids decreased hepatic fat content. Probiotics gave mixed results, whereas reduced fructose consumption did not improve primary outcome measures. A low glycaemic load diet and a low-fat diet appeared equally effective in decreasing hepatic fat content and transaminases. Most studies were deemed neutral as assessed by the American Dietetic Association Quality Criteria Checklist. CONCLUSIONS: The limited evidence base inhibits the prescription of specific dietary and/or lifestyle strategies for clinical practice. General healthy eating and physical activity guidelines, promoting weight loss, should remain first-line treatment until high-quality evidence emerges that support specific interventions that offer additional clinical benefit.
Assuntos
Terapia por Exercício/métodos , Hepatopatia Gordurosa não Alcoólica/terapia , Terapia Nutricional/métodos , Criança , Terapia Combinada , Suplementos Nutricionais , Humanos , Pediatria , Redução de PesoRESUMO
A phospho-null Ala substitution at protein kinase C (PKC)-targeted cardiac troponin I (cTnI) S43/45 reduces myocyte and cardiac contractile function. The goal of the current study was to test whether cTnIS43/45N is an alternative, functionally conservative substitution in cardiac myocytes. Partial and more extensive endogenous cTnI replacement was similar at 2 and 4 days after gene transfer, respectively, for epitope-tagged cTnI and cTnIS43/45N. This replacement did not significantly change thin filament stoichiometry. In functional studies, there were no significant changes in the amplitude and/or rates of contractile shortening and re-lengthening after this partial (2 days) and extensive (4 days) replacement with cTnIS43/45N. The cTnIS43/45N substitution also was not associated with adaptive changes in the myocyte Ca(2+) transient or in phosphorylation of the protein kinase A and C-targeted cTnIS23/24 site. These results provide evidence that cTnIS43/45N is a functionally conservative substitution, and may be appropriate for use as a phospho-null in rodent models designed for studies on PKC modulation of cardiac performance.
Assuntos
Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Quinase C/metabolismo , Troponina I/metabolismo , Substituição de Aminoácidos , Animais , Cálcio/química , Cálcio/metabolismo , Epitopos/química , Técnicas de Transferência de Genes , Mutagênese Sítio-Dirigida , Contração Miocárdica , Fosforilação , Ratos , Ratos Sprague-Dawley , Sarcômeros/metabolismo , Transdução de Sinais , Troponina I/genéticaRESUMO
BACKGROUND: Immunization advice services can support health professionals by providing rapid access to accurate and reliable current information and advice. The Vaccine Advice for Clinicians Service (VACCSline) is a service for health professionals working within the Thames Valley Area of the UK. METHODS: We reviewed all 4299 enquiries received by VACCSline over 3 years. Queries were summarized by vaccine type and topic of enquiry. Associations with profession and workplace of the enquirer were tested using Fisher's exact tests. RESULTS: Incomplete immunization status and non-UK schedules were the most common topics of enquiry. Practice nurses were the main service users followed by doctors. Enquiries varied by professional role. Alterations to the immunization programme led to temporary changes to enquiry content and some more persistent adjustments in the balance of enquiries were identified, such as an increase in enquiries relating to vaccination in pregnancy. CONCLUSIONS: The content of enquiries to VACCSline is broad, confirming the need for immunizers to have a wide knowledge base and access to specialist advice to assist with complex scenarios. Systematic data capture provided intelligence to guide training and materials to support immunizers. A wider networked application of this approach could improve support for immunizers.