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1.
J Clin Med ; 12(24)2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38137615

RESUMO

Hepatitis C virus (HCV) infection can lead to hepatic fibrosis. The advent of direct-acting antivirals (DAAs) has substantially improved sustained virological response (SVR) rates. In this context, kidney transplant recipients (KTRs) are of particular interest due to their higher HCV infection rates and uncertain renal excretion and bioavailability of DAAs. We investigated liver stiffness after DAA treatment in 15 HCV-infected KTRs using ultrasound shear wave elastography (SWE) in comparison with magnetic resonance elastography (MRE). KTRs were treated with DAAs (daclatasvir and sofosbuvir) for three months and underwent SWE at baseline, end of therapy (EOT), and 3 (EOT+3) and 12 months (EOT+12) after EOT. Fourteen patients achieved SVR12. Shear wave speed (SWS)-as a surrogate parameter for tissue stiffness-was substantially lower at all three post-therapeutic timepoints compared with baseline (EOT: -0.42 m/s, p < 0.01; CI = -0.75--0.09, EOT+3: -0.43 m/s, p < 0.01; CI = -0.75--0.11, and EOT+12: -0.52 m/s, p < 0.001; CI = -0.84--0.19), suggesting liver regeneration after viral eradication and end of inflammation. Baseline SWS correlated positively with histopathological fibrosis scores (r = 0.48; CI = -0.11-0.85). Longitudinal results correlated moderately with APRI (r = 0.41; CI = 0.12-0.64) but not with FIB-4 scores (r = 0.12; CI = -0.19-0.41). Although higher on average, SWE-derived measurements correlated strongly with MRE (r = 0.64). In conclusion, SWE is suitable for non-invasive therapy monitoring in KTRs with HCV infection.

2.
Quant Imaging Med Surg ; 13(8): 4792-4805, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581033

RESUMO

Background: Although there is growing evidence that functional involvement and structural changes of mesenteric adipose tissue (MAT) influence the course of Crohn's disease (CD), its viscoelastic properties remain elusive. Therefore, we aimed to investigate the viscoelastic properties of MAT in CD using magnetic resonance elastography (MRE), providing reference values for CD diagnosis. Methods: In this prospective proof-of-concept study, 31 subjects (CD: n=11; healthy controls: n=20) were consecutively enrolled in a specialized care center for inflammatory bowel diseases (tertiary/quaternary care). Inclusion criteria for the CD patients were a clinically and endoscopically established diagnosis of CD based on the clinical record, absence of other concurrent bowel diseases, scheduled surgery for the following day, and age of at least 18 years. Diagnoses were confirmed by histological analysis of the resected bowel the day after MRE. Subjects were investigated using MRE at 1.5-T with frequencies of 40-70 Hz. To retrieve shear wave speed (SWS), volumes of interest (VOIs) in MAT were drawn adjacent to CD lesions (MATCD) and on the opposite side without adjacent bowel lesions in patients (MATCD_Opp) and controls (MATCTRL). The presented study is not registered in the clinical trial platform. Results: A statistically significant decrease in mean SWS of 7% was found for MATCD_Opp vs. MATCTRL (0.76±0.05 vs. 0.82±0.04 m/s, P=0.012), whereas there was a nonsignificant trend with an 8% increase for MATCD vs. MATCD_Opp (0.82±0.07 vs. 0.76±0.05 m/s, P=0.098) and no difference for MATCD vs. MATCTRL. Preliminary area under the receiver operating characteristic curve (AUC) analysis showed diagnostic accuracy in detecting CD to be excellent for SWS of MATCD_Opp [AUC =0.82; 95% confidence interval (CI): 0.64-0.96] but poor for SWS of MATCD (AUC =0.52; 95% CI: 0.34-0.73). Conclusions: This study demonstrates the feasibility of MRE of MAT and presents preliminary reference values for CD patients and healthy controls. Our results motivate further studies for the biophysical characterization of MAT in inflammatory bowel disease.

3.
J Magn Reson Imaging ; 55(3): 815-822, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34254389

RESUMO

BACKGROUND: While MR enterography allows detection of inflammatory bowel disease (IBD), the findings continue to be of limited use in guiding treatment-medication vs. surgery. PURPOSE: To test the feasibility of MR elastography of the gut in healthy volunteers and IBD patients. STUDY TYPE: Prospective pilot. POPULATION: Forty subjects (healthy volunteers: n = 20, 37 ± 14 years, 10 women; IBD patients: n = 20 (ulcerative colitis n = 9, Crohn's disease n = 11), 41 ± 15 years, 11 women). FIELD STRENGTH/SEQUENCE: Multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 T with drive frequencies of 40, 50, 60, and 70 Hz. ASSESSMENT: Maps of shear-wave speed (SWS, in m/s) and loss angle (φ, in rad), representing stiffness and solid-fluid behavior, respectively, were generated using tomoelastography data processing. Histopathological analysis of surgical specimens was used as reference standard in patients. STATISTICAL TESTS: Unpaired t-test, one-way analysis of variance followed by Tukey post hoc analysis, Pearson's correlation coefficient and area under the receiver operating characteristic curve (AUC) with 95%-confidence interval (CI). Significance level of 5%. RESULTS: MR elastography was feasible in all 40 subjects (100% technical success rate). SWS and φ were significantly increased in IBD by 21% and 20% (IBD: 1.45 ± 0.14 m/s and 0.78 ± 0.12 rad; healthy volunteers: 1.20 ± 0.14 m/s and 0.65 ± 0.06 rad), whereas no significant differences were found between ulcerative colitis and Crohn's disease (P = 0.74 and 0.90, respectively). In a preliminary assessment, a high diagnostic accuracy in detecting IBD was suggested by an AUC of 0.90 (CI: 0.81-0.96) for SWS and 0.84 (CI: 0.71-0.95) for φ. DATA CONCLUSION: In this pilot study, our results demonstrated the feasibility of MR elastography of the gut and showed an excellent diagnostic performance in predicting IBD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.


Assuntos
Colite Ulcerativa , Doença de Crohn , Técnicas de Imagem por Elasticidade , Doença de Crohn/diagnóstico por imagem , Técnicas de Imagem por Elasticidade/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos
4.
Front Bioeng Biotechnol ; 10: 1042711, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36698634

RESUMO

The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver's metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver's metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography-mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into 'stiff' and 'soft' subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.

5.
J Clin Med ; 10(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34884335

RESUMO

To evaluate the outcomes of kidney transplantations (KTs) in the Eurotransplant Senior Program (ESP) with a focus on the very old, defined as recipients ≥75 years. This retrospective clinical study included 85 patients, who under the ESP protocol underwent deceased donor kidney transplantation from January 2010 to July 2018 at the Charité-Universitätsmedizin Berlin in Germany. Recipients were divided in three age groups, i.e., Group 65-69, Group 70-74, Group ≥75, and compared. Prognostic risk factors for short and long-term outcomes of kidney transplantations were investigated. Graft survival at 1 and 5 years were respectively 90.7% and 68.0% for group 65-69, 88.9% and 76.2% for Group 70-74, and 100% and 71.4% for Group ≥75. Patient survival at 1 and 5 years were respectively 92.9% and 68.0% for Group 65-69, 85.7% and 61.5% for Group 70-74 and 100% and 62.5% for Group ≥75. Serum creatinine did not significantly differ between the three groups, with the exception of serum creatinine at 1 year. Increased recipient age and prolonged time on dialysis correlated with increased occurrence of postoperative complication. An increase in BMI, pretransplant diabetes mellitus and prolonged time on dialysis correlated with the occurrence of delayed graft function (DGF). History of smoking was identified as an independent risk factor for events of rejection. Increased human leukocyte antigen mismatches (HLA-MM) and prolonged cold ischemia time (CIT) correlated with higher rates of intensive care unit (ICU) treatment. This study supports kidney transplantations for the very old. End-stage renal disease (ESRD) patients ≥75 years of age who underwent kidney transplantation experienced comparable results to their younger counterparts. A comprehensive evaluation of ESRD patients with consideration of prognostic risk factor is the most suitable mean of identifying adequate kidney transplant candidates.

6.
Cancers (Basel) ; 13(20)2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34680334

RESUMO

PURPOSE: To evaluate the diagnostic performance of tomoelastography in differentiating pancreatic neuroendocrine tumors (PNETs) from healthy pancreatic tissue and to assess the prediction of tumor aggressiveness by correlating PNET stiffness with PET derived asphericity. METHODS: 13 patients with PNET were prospectively compared to 13 age-/sex-matched heathy volunteers (CTR). Multifrequency MR elastography was combined with tomoelastography-postprocessing to provide high-resolution maps of shear wave speed (SWS in m/s). SWS of pancreatic neuroendocrine tumor (PNET-T) were compared with nontumorous pancreatic tissue in patients with PNET (PNET-NT) and heathy pancreatic tissue (CTR). The diagnostic performance of tomoelastography was evaluated by ROC-AUC analysis. PNET-SWS correlations were calculated with Pearson's r. RESULTS: SWS was higher in PNET-T (2.02 ± 0.61 m/s) compared to PNET-NT (1.31 ± 0.18 m/s, p < 0.01) and CTR (1.26 ± 0.09 m/s, p < 0.01). An SWS-cutoff of 1.46 m/s distinguished PNET-T from PNET-NT (AUC = 0.89; sensitivity = 0.85; specificity = 0.92) and a cutoff of 1.49 m/s differentiated pancreatic tissue of CTR from PNET-T (AUC = 0.96; sensitivity = 0.92; specificity = 1.00). The SWS of PNET-T was positively correlated with PET derived asphericity (r = 0.81; p = 0.01). CONCLUSIONS: Tomoelastography provides quantitative imaging markers for the detection of PNET and the prediction of greater tumor aggressiveness by increased stiffness.

7.
J Clin Med ; 10(3)2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33535495

RESUMO

Besides the liver, hepatitis C virus (HCV) infection also affects kidney allografts. The aim of this study was to longitudinally evaluate viscoelasticity changes in the liver and in kidney allografts in kidney transplant recipients (KTRs) with HCV infection after treatment with direct-acting antiviral agents (DAAs). Fifteen KTRs with HCV infection were treated with DAAs (daclatasvir and sofosbuvir) for 3 months and monitored at baseline, end of treatment (EOT), and 3 (FU1) and 12 (FU2) months after EOT. Shear-wave speed (SWS) and loss angle of the complex shear modulus (φ), reflecting stiffness and fluidity, respectively, were reconstructed from multifrequency magnetic resonance elastography data with tomoelastography post-processing. After virus elimination by DAAs, hepatic stiffness and fluidity decreased, while kidney allograft stiffness and fluidity increased compared with baseline (hepatic stiffness change at FU1: -0.14 m/s, p < 0.01, and at FU2: -0.11 m/s, p < 0.05; fluidity at FU1: -0.05 rad, p = 0.04 and unchanged at FU2: p = 0.20; kidney allograft stiffness change at FU1: +0.27 m/s, p = 0.01, and at FU2: +0.30 m/s, p < 0.01; fluidity at FU1 and FU2: +0.06 rad, p = 0.02). These results suggest the restoration of mechanically sensitive structures and functions in both organs. Tomoelastography can be used to monitor the therapeutic results of HCV treatment non-invasively on the basis of hepatic and renal viscoelastic parameters.

8.
Eur Radiol ; 31(5): 3366-3374, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33125553

RESUMO

OBJECTIVES: To prospectively investigate the stiffness and fluidity of pancreatic ductal adenocarcinoma (PDAC) and autoimmune pancreatitis (AIP) with tomoelastography, and to evaluate its diagnostic performance in distinguishing the two entities. METHODS: Tomoelastography provided high-resolution maps of shear wave speed (c in m/s) and phase angle (φ in rad), allowing mechanical characterization of the stiffness and fluidity properties of the pancreas. Forty patients with untreated PDAC and 33 patients with untreated AIP who underwent diagnostic pancreatic MRI at 3-T together with multifrequency MR elastography and tomoelastography data processing were prospectively enrolled. Ten healthy volunteers served as controls. Two radiologists and a technician measured pancreatic stiffness and fluidity independently. The two radiologists also independently evaluated the patients' conventional MR sequences using the following diagnostic score: 1, definitely PDAC; 2, probably PDAC; 3, indeterminate; 4, probably AIP; and 5, definitely AIP. Interobserver agreement was assessed. Stiffness and fluidity of PDAC, AIP, and healthy pancreas, as well as diagnostic performance of tomoelastography and conventional MRI, were compared. RESULTS: AIP showed significantly lower stiffness and fluidity than PDAC and significantly higher stiffness and fluidity than healthy pancreas. Pancreatic fluidity was not influenced by secondary obstructive changes. The intraclass correlation coefficient for pancreatic stiffness and fluidity by the 3 readers was near-perfect (0.951-0.979, all p < 0.001). Both stiffness and fluidity allowed distinguishing PDAC from AIP. AUCs were 0.906 for stiffness, 0.872 for fluidity, and 0.842 for conventional MRI. CONCLUSIONS: Pancreatic stiffness and fluidity both allow differentiation of PDAC and AIP with high accuracy. KEY POINTS: • AIP showed significantly lower stiffness and fluidity than PDAC and significantly higher stiffness and fluidity than healthy pancreas. • Both stiffness and fluidity allowed distinguishing PDAC from AIP. • Pancreatic fluidity could distinguish malignancy from non-malignant secondary obstructive changes.


Assuntos
Doenças Autoimunes , Pancreatite Autoimune , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Doenças Autoimunes/diagnóstico por imagem , Carcinoma Ductal Pancreático/diagnóstico , Diagnóstico Diferencial , Humanos , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem
9.
Invest Radiol ; 55(12): 769-774, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32796197

RESUMO

OBJECTIVES: Estimations of tumor volume and boundary in pancreatic ductal adenocarcinoma (PDAC) are crucial for surgery planning. The aim of the study is to evaluate tomoelastography for detection of PDAC and quantification of PDAC volume based on tissue stiffness. MATERIALS AND METHODS: From March 2018 to December 2019, a total of 102 participants (30 healthy participants and 72 patients with histologically proven PDAC) were prospectively enrolled in a multicenter study. Multifrequency magnetic resonance elastography was combined with tomoelastography postprocessing to generate maps of shear wave speed (SWS) depicting highly resolved anatomical details of tissue stiffness. Subregional analysis of pancreatic head, body, and tail and reproducibility tests were performed in healthy participants, whereas tumorous (PDAC-T) and nontumorous (PDAC-NT) pancreatic tissue analysis was conducted in patients. In all patients, tumor volumes measured by computed tomography (CT) were compared with SWS-derived volumes. In addition, in 32 patients, tumor sizes were evaluated by macroscopy after resection. RESULTS: Tumor volumes were quantified in 99% and 87% of all cases with tomoelastography and CT, respectively. Pancreatic SWS was highly reproducible (repeatability coefficient = 0.12) and did not vary regionally or with patient age, sex, or body mass index (all P > 0.08). Shear wave speed was higher in PDAC-T (2.08 ± 0.38 m/s) than in healthy (1.25 ± 0.09 m/s; P < 0.001) and PDAC-NT (1.28 ± 0.14 m/s; P < 0.001) participants. A threshold of 1.47 m/s separated PDAC-T from healthy volunteers (area under the curve = 1.0, sensitivity = 100%, specificity = 100%), while 1.49 m/s separated PDAC-T from PDAC-NT with high accuracy (area under the curve = 0.99, sensitivity = 90%, specificity = 100%). Tomoelastography-derived tumor volume correlated with CT volume (r = 0.91, P < 0.001) and ex vivo tumor volume (r = 0.66, P < 0.001). CONCLUSIONS: Tomoelastography provides a quantitative imaging marker for tissue stiffness depicting PDAC boundaries and separates PDAC from unaffected pancreatic tissue.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Técnicas de Imagem por Elasticidade , Fenômenos Mecânicos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Carga Tumoral , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
10.
Cancer Res ; 79(22): 5704-5710, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31551364

RESUMO

Patients with increased liver stiffness have a higher risk of developing cancer, however, the role of fluid-solid tissue interactions and their contribution to liver tumor malignancy remains elusive. Tomoelastography is a novel imaging method for mapping quantitatively the solid-fluid tissue properties of soft tissues in vivo. It provides high resolution and thus has clear clinical applications. In this work we used tomoelastography in 77 participants, with a total of 141 focal liver lesions of different etiologies, to investigate the contributions of tissue stiffness and fluidity to the malignancy of liver tumors. Shear-wave speed (c) as surrogate for tissue stiffness and phase-angle (φ) of the complex shear modulus reflecting tissue fluidity were abnormally high in malignant tumors and allowed them to be distinguished from nontumorous liver tissue with high accuracy [c: AUC = 0.88 with 95% confidence interval (CI) = 0.83-0.94; φ: AUC = 0.95, 95% CI = 0.92-0.98]. Benign focal nodular hyperplasia and hepatocellular adenoma could be distinguished from malignant lesions on the basis of tumor stiffness (AUC = 0.85, 95% CI = 0.72-0.98; sensitivity = 94%, 95% CI = 89-100; and specificity = 85%, 95% CI = 62-100), tumor fluidity (AUC = 0.86, 95% CI = 0.77-0.96; sensitivity = 83%, 95% CI = 72-93; and specificity = 92%, 95% CI = 77-100) and liver stiffness (AUC = 0.84, 95% CI = 0.74-0.94; sensitivity = 72%, 95% CI = 59-83; and specificity = 88%, 95% CI = 69-100), but not on the basis of liver fluidity. Together, hepatic malignancies are characterized by stiff, yet fluid tissue properties, whereas surrounding nontumorous tissue is dominated by solid properties. Tomoelastography can inform noninvasively on the malignancy of suspicious liver lesions by differentiating between benign and malignant lesions with high sensitivity based on stiffness and with high specificity based on fluidity. SIGNIFICANCE: Solid-fluid tissue properties measured by tomoelastography can distinguish malignant from benign masses with high accuracy and provide quantitative noninvasive imaging biomarkers for liver tumors.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , Fígado/patologia , Adenoma de Células Hepáticas/diagnóstico , Adenoma de Células Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Técnicas de Imagem por Elasticidade/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Adulto Jovem
11.
Radiology ; 292(3): 676-684, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31287390

RESUMO

Background Glomerulonephritis refers to renal diseases characterized by glomerular and tubulointerstitial fibrosis. Multifrequency US time-harmonic elastography enables the noninvasive quantification of tissue elasticity. Purpose To assess the diagnostic performance of US time-harmonic elastography for the early detection of glomerulonephritis. Materials and Methods From August 2016 through May 2017, study participants with biopsy-proven glomerulonephritis were prospectively examined with US time-harmonic elastography. Participants were subdivided according to chronic kidney disease (CKD) stage. All participants underwent elastography of both kidneys to generate full-field-of-view maps of renal shear wave speed (SWS). SWS was determined separately for the whole renal parenchyma, cortex, and medulla and was correlated with quantitative B-mode findings such as renal length and parenchymal thickness. Diagnostic performance of renal elastography was assessed with receiver operating characteristic curve analysis. Results Fifty-three participants with glomerulonephritis (mean age ± standard deviation, 49 years ± 14) and 30 healthy volunteers (mean age, 37 years ± 11) were evaluated. Age-adjusted renal SWS was lower in participants with glomerulonephritis than in healthy volunteers in the parenchyma, cortex, and medulla, with mean values of 1.55 m/sec (95% confidence interval [CI]: 1.51 m/sec, 1.59 m/sec) and 1.69 m/sec (95% CI: 1.64 m/sec, 1.74 m/sec; P < .001), respectively, in parenchyma, 1.80 m/sec (95% CI: 1.75 m/sec, 1.84 m/sec) and 2.08 m/sec (95% CI: 2.02 m/sec, 2.13 m/sec; P < .001) in cortex, and 1.25 m/sec (95% CI: 1.21 m/sec, 1.29 m/sec) and 1.33 (95% CI: 1.27 m/sec, 1.38 m/sec; P = .03) in medulla. Age-adjusted renal cortex SWS was lower in participants with glomerulonephritis and stage 1 CKD (preserved renal function) than in healthy volunteers (mean, 1.88 [95% CI: 1.81, 1.96] vs 2.08 [95% CI: 2.02, 2.13]; P < .001). In participants with CKD, renal cortex SWS values showed a positive association with estimated glomerular filtration rate (n = 39; r = 0.56; P < .001). Exploratory diagnostic performance of US time-harmonic elastography (area under the receiver operating characteristic curve [AUC], 0.89; 95% CI: 0.82, 0.97) outperformed that of B-mode parameters such as parenchymal thickness (AUC, 0.64; 95% CI: 0.51, 0.77; P < .001) and renal length (AUC, 0.55; 95% CI: 0.40, 0.68; P < .001) in identifying glomerulonephritis. Conclusion US time-harmonic elastography depicts abnormal renal stiffness in glomerulonephritis, particularly among patients with early disease and preserved renal function. Advanced chronic kidney disease is associated with further cortical softening. Time-harmonic elastography outperforms B-mode-based size quantification. © RSNA, 2019 Online supplemental material is available for this article.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Glomerulonefrite/diagnóstico por imagem , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Adulto Jovem
12.
BMC Nephrol ; 20(1): 36, 2019 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-30717681

RESUMO

BACKGROUND: Only a few prospective trials exist regarding the use of novel direct-acting antiviral agents (DAAs) in kidney transplant recipients (KTR) with chronic hepatitis C virus (HCV) infection. METHODS: This prospective single-center trial evaluated treatment with daclatasvir (DCV) and sofosbuvir (SOF) over 12 weeks in 16 adult chronic HCV infected KTR and eGFR > 30 ml/min/1.73m2. Primary endpoint was sustained virological response 12 weeks after end of therapy (SVR12). Beside baseline liver biopsy, hepatic function and glucose metabolism were regularly assessed. RESULTS: Four of 16 study patients had previously failed interferon-based HCV treatment. Liver biopsy showed mostly moderate fibrosis score before therapy with DCV/SOF was initiated at a median of 10.3 years after transplantation. In total, 15 of 16 KTR achieved SVR12. One patient showed early viral relapse because of resistance-associated variants (RAVs) in the HCV NS5A region. Rescue treatment with SOF/velpatasvir/voxilaprevir resulted in SVR12. DAAs treatment led to significant improvement of liver metabolism and glucose tolerance accompanied with no therapy-associated major adverse events and excellent tolerability. CONCLUSIONS: Our study demonstrates safety, efficacy and functional benefit of DCV/SOF treatment in KTR with chronic HCV infection. We provide data on rescue strategies for treatment failures due to present RAVs and amelioration of hepatic function and glucose tolerance. TRIAL REGISTRATION: Registry name: European Clinical Trials Register; Trial registry number (Eudra-CT): 2014-004551-32 , Registration date: Aug 28th 2015.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Transplante de Rim , Sofosbuvir/uso terapêutico , Viremia/tratamento farmacológico , Adulto , Idoso , Ácidos Aminoisobutíricos , Antivirais/administração & dosagem , Biópsia por Agulha , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/uso terapêutico , Carbamatos/administração & dosagem , Carbamatos/farmacologia , Carbamatos/uso terapêutico , Ciclopropanos , Quimioterapia Combinada , Feminino , Intolerância à Glucose/induzido quimicamente , Hepacivirus/efeitos dos fármacos , Hepacivirus/isolamento & purificação , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Lactamas Macrocíclicas , Leucina/análogos & derivados , Fígado/patologia , Compostos Macrocíclicos/administração & dosagem , Compostos Macrocíclicos/farmacologia , Compostos Macrocíclicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prolina/análogos & derivados , Estudos Prospectivos , Pirrolidinas , Quinoxalinas , RNA Viral/sangue , Terapia de Salvação , Sofosbuvir/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Carga Viral , Proteínas não Estruturais Virais/antagonistas & inibidores , Viremia/complicações , Viremia/patologia
13.
Acta Radiol ; 59(9): 1139-1145, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29249167

RESUMO

Background Monitoring of renal allograft function is essential for early identification of dysfunction and improvement of kidney transplant (KTX) outcome. Purpose To non-invasively assess renal stiffness in KTX recipients using ultrasound shear wave elastography (USE) in correlation with multifrequency magnetic resonance elastography (MRE), renal allograft function, and renal microvascular flow determined using a novel ultrasound microvascular imaging technique. Material and Methods This prospective study investigated 25 KTXs (functional KTX [FCT], n = 14; chronic KTX insufficiency [DYS], n = 11) in 20 KTX recipients (mean age = 43 ± 14 years). USE was performed using a high-frequency broadband linear transducer and compared with MRE. Shear wave velocity (SWV) was correlated with the estimated glomerular filtration rate (eGFR). Qualitative differences in renal microvascular flow were obtained using SMI. Results FCT had higher SWV than DYS in both cortex and pyramids (cortex, FCT: 3.75 ± 0.82 m/s vs. DYS: 2.79 ± 0.73 m/s, P = 0.0002; pyramid, FCT: 2.89 ± 0.46 m/s vs. DYS: 2.39 ± 0.34 m/s, P = 0.044). Cutoff values of 3.265 m/s for cortex, 2.535 m/s for pyramids, and 2.985 m/s for combined non-hilar parenchyma provided sensitivities of 72.7%, 77.8%, and 90.9% and specificities of 71.4%, 78.6%, and 85.7% for detecting renal allograft dysfunction with area under the receiver operating characteristic curve (AUC) values of 0.831, 0.841, 0.925 (95% confidence interval [CI] = 0.67-0.99, 0.66-1.02, 0.83-1.03). USE correlated positively with eGFR ( r = 0.741, P = 0.0004) and with MRE-derived SWV ( r = 0.562, P = 0.004). Renal microvascular flow was decreased in DYS. Conclusion USE is sensitive to renal allograft dysfunction, which is characterized by reduced SWV and renal perfusion. USE has higher image resolution than MRE, while MRE has slightly better diagnostic accuracy.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Transplante de Rim , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Testes de Função Renal , Masculino , Microcirculação , Pessoa de Meia-Idade , Estudos Prospectivos , Transdutores
14.
Clin Rheumatol ; 34(6): 1079-84, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25896531

RESUMO

Steroid injection of the sacroiliac joints is widely used for the management of active sacroiliitis in patients with spondyloarthritis (SpA). The aims of this study were to prospectively investigate the effectiveness of corticosteroid injection of the sacroiliac joints and to identify factors determining positive and negative outcome. Twenty-nine patients (18 female, 11 male) suffering from sacroiliitis were treated by computed tomography (CT)-guided administration of 40 or 60 mg triamcinolone acetonide per joint. Clinical outcome of the intervention was determined using a visual analog scale from days 1 to 7 as well as after 1, 3, and 6 months. Patients were grouped according to intra-articular (n = 22) and peri-articular positions (n = 7) of the tip of the puncture needle. In patients with intra-articular needle position (76 %), the mean pain score decreased significantly from 7.3 (±1.9) to 3.9 (±3.4) at day 7 and to 3.9 (±3.4) after 1 month, 4.2 (±3.3) after 3 months, and 5.2 (±2.9) after 6 months. The group with peri-articular needle position (24 %) did not show a statistically significant pain reduction throughout the entire 6-month follow-up period. A substantial reduction of inflammatory back pain (reduction of at least 4 visual analog scale (VAS) points) was reported by 55 % of patients after 3 months and 45 % of patients after 6 months. Our results demonstrate that intra-articular CT-guided steroid instillation can achieve sufficient pain and symptom control for 6 months in patients suffering from active sacroiliitis. It is therefore recommended to perform this intervention under appropriate image guidance to ensure proper positioning of the needle tip.


Assuntos
Glucocorticoides/uso terapêutico , Injeções Intra-Articulares/métodos , Articulação Sacroilíaca/diagnóstico por imagem , Sacroileíte/tratamento farmacológico , Espondiloartropatias/tratamento farmacológico , Triancinolona/uso terapêutico , Adulto , Artrite Psoriásica/diagnóstico por imagem , Artrite Psoriásica/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Garantia da Qualidade dos Cuidados de Saúde , Sacroileíte/diagnóstico por imagem , Espondiloartropatias/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/tratamento farmacológico , Cirurgia Assistida por Computador , Tomografia Computadorizada Espiral , Resultado do Tratamento
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