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The prevalence of atherosclerosis has increased significantly in the recent years due to sedentary lifestyle and high-fat diet. However, the association between saturated fat intake and the increased risk for atherosclerotic cardiovascular diseases remains heavily debated. Lauric acid belongs to the saturated fatty acid group and its unique medium chain fatty acid properties are proven to be beneficial to humans in many ways. Thus, the aim of this project is to investigate the effect of lauric acid on the expression of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes-ADAMTS-1, ADAMTS-4, and ADAMTS-5-in macrophages. These genes encode for proteases that participate in the extracellular matrix remodeling and they play important roles in the vulnerability of atherosclerotic plaque. Here, we show that the treatment of 20 µM of lauric acid successfully reduced both transcriptional and translational expressions of these genes in THP-1 differentiated macrophages after 24-h incubation. Further cell signaling experiments using a panel of kinase inhibitors and phosphorylated antibodies proved that lauric acid down-regulated ADAMTS-1 by reducing the activation of PI3K and JNK at Tyr458 and Tyr185, respectively. Finally, JNK1 siRNA knockdown assay confirmed that ADAMTS-1 was regulated through JNK pathway, and lauric acid interfered with this pathway to down-regulate ADAMTS-1 expression. Although preliminary, this present study indicates that lauric acid has the potential to stabilize atherosclerotic plaque and may prevent thrombosis by interfering with the ADAMTS-1 expression through PI3K/JNK pathways.
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Proteína ADAMTS1/metabolismo , Aterosclerosis/metabolismo , Ácidos Láuricos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Proteína ADAMTS1/biosíntesis , Proteína ADAMTS1/genética , Regulación hacia Abajo/efectos de los fármacos , Expresión Génica , Humanos , Macrófagos/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloendopeptidasas/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Células THP-1RESUMEN
BACKGROUND: Hepatocyte-specific gadolinium based contrast agents (HSCA) provide substantial information for the classification of liver lesions in magnetic resonance imaging (MRI). However, breathing artifacts which reduce image quality and diagnostic confidence of hepatobiliary phase acquisitions are regularly observed in clinical routine. The aim of this study was to evaluate two approaches to reduce breathing artifacts for hepatobiliary phase imaging. METHODS: Twenty minutes after administration of a HSCA (gadoxetic acid), a T1-weighted VIBE sequence with radial k-space sampling (radialVIBE, 180 s acquisition time in free breathing) and a highly accelerated Cartesian VIBE with Dixon fat separation (CD-VIBE, CAIPIRINHA acceleration with r = 2 × 2, breath-hold 8-10 s) were acquired in 35 patients (12 female, 57 ± 13 years), who showed breath-holding difficulties in early phases of the examinations. Image quality (image sharpness, noise, artifacts, homogeneity of fat saturation, bile duct delineation and overall image quality) as well as conspicuity and liver-to-lesion signal intensity (SI) ratios of focal liver lesions were assessed for both radial- and CD-VIBE. RESULTS: Overall image quality was rated good to excellent for both sequences, while CD-VIBE was preferred in most cases. Though radialVIBE received better results regarding image noise and artifacts, both sequences were rated equally regarding bile duct delineation and sharpness. Focal liver lesion (n = 42) conspicuity was rated significantly better and SI-ratios were significantly higher on CD-VIBE (2.45 ± 1.44 vs. 1.61 ± 0.70 in radialVIBE, p = 0.0001). In three patients, CD-VIBE was rated non-diagnostic due to severe breathing artifacts, while radialVIBE was diagnostic in those patients. CONCLUSION: Both highly accelerated Cartesian as well as radial acquisition techniques provide good to excellent image quality in hepatobiliary phase MRI. In comparison, CD-VIBE offered better overall image quality and liver lesion conspicuity. However, radialVIBE was a valuable alternative in patients unable to sustain even short breath-hold intervals. Further studies including lager patient cohorts are desirable to allow a transfer of these results to a general patient population.
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Sistema Biliar/diagnóstico por imagen , Interpretación de Imagen Asistida por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Contencion de la Respiración , Medios de Contraste/metabolismo , Femenino , Gadolinio DTPA/metabolismo , Humanos , Imagenología Tridimensional , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: We report the first case of an intraoperative radiotherapy (IORT) in a patient with recurrent glioblastoma multiforme (GBM) who was followed up with a novel magnetic resonance imaging (MRI) method-(23)Na-MRI-in comparison to a standard contrast-enhanced (1)H-MRI and (18)F-FET-PET. METHODS: A 56-year-old female patient with diagnosed GBM in July 2012 underwent tumor resection, radiochemotherapy, and three cycles of chemotherapy. After a relapse, 6 months after the initial diagnosis, an IORT was recommended which was performed in March 2013 using the INTRABEAM system (Carl Zeiss Meditec AG, Germany) with a 3-cm applicator and a surface dose of 20 Gy. Early post-operative contrast-enhanced and 1-month follow-up (1)H-MRI and a (18)F-FET-PET were performed. In addition, an IRB-approved (23)Na-MRI was performed on a 3.0-T MR scanner (MAGNETOM TimTrio, Siemens Healthcare, Germany). RESULTS: After re-surgery and IORT in March 2013, only a faint contrast enhancement but considerable surrounding edema was visible at the medio-posterior resection margins. In April 2013, new and progressive contrast enhancement, edema, (23)Na content, and increased uptake in the (18)F-FET-PET were visible, indicating tumor recurrence. Increased sodium content within the area of contrast enhancement was found in the (23)Na-MRI, but also exceeding this area, very similar to the increased uptake depicted in the (18)F-FET-PET. The clearly delineable zone of edema in both examinations exhibits a lower (23)Na content compared to areas with suspected proliferating tumor tissue. CONCLUSION: (23)Na-MRI provided similar information in the suspicious area compared to (18)F-FET-PET, exceeding conventional (1)H-MRI. Still, (23)Na-MRI remains an investigational technique, which is worth to be further evaluated.
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Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Glioblastoma/patología , Glioblastoma/terapia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Terapia Combinada , Medios de Contraste , Irradiación Craneana/métodos , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Radiofármacos , Isótopos de Sodio/uso terapéutico , Resultado del TratamientoRESUMEN
INTRODUCTION: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. METHODS: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. RESULTS: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. CONCLUSION: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.
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Enfermedades del Prematuro , Meningitis , Sepsis , Lactante , Humanos , Recién Nacido , Recien Nacido Prematuro , Estudios Retrospectivos , Edad Gestacional , Canadá/epidemiología , Hemorragia Cerebral/complicaciones , Hemorragia Cerebral/epidemiología , Sepsis/complicaciones , Enfermedades del Prematuro/epidemiologíaRESUMEN
CAR T-cell therapy is a promising approach for cancer treatment, utilizing a patient's own T-cells (autologous cell) or T-cells from a healthy donor (allogeneic cell) to target and destroy cancer cells. Over the last decade, significant advancements have been made in this field, including the development of novel CAR constructs, improved understanding of biology and mechanisms of action, and expanded clinical applications for treating a wider range of cancers. In this review, we provide an overview of the steps involved in the production of CAR T-cells and their mechanism of action. We also introduce different CAR T-cell therapies available, including their implementation, dosage, administration, treatment cost, efficacy, and resistance. Common side effects of CAR T-cell therapy are also discussed. The CAR T-cell products highlighted in this review are FDA-approved products, which include Kymriah® (tisagenlecleucel), Tecartus® (brexucabtagene autoleucel), Abecma® (Idecabtagene vicleucel), Breyanzi® (lisocabtagene maraleucel), and Yescarta® (axicabtagene ciloleucel). In conclusion, CAR T-cell therapy has made tremendous progress over the past decade and has the potential to revolutionize cancer treatment. This review paper provides insights into the progress, challenges, and future directions of CAR T-cell therapy, offering valuable information for researchers, clinicians, and patients.
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Inmunoterapia Adoptiva , Neoplasias , Receptores Quiméricos de Antígenos , United States Food and Drug Administration , Humanos , Inmunoterapia Adoptiva/métodos , Neoplasias/terapia , Neoplasias/inmunología , Receptores Quiméricos de Antígenos/inmunología , Estados Unidos , Linfocitos T/inmunología , AnimalesAsunto(s)
Núcleos Cerebelosos/efectos de los fármacos , Medios de Contraste/farmacología , Meglumina/farmacología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Compuestos Organometálicos/farmacología , Adulto , Núcleos Cerebelosos/diagnóstico por imagen , Femenino , Gadolinio/farmacología , Humanos , Compuestos Macrocíclicos/farmacología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: To evaluate the feasibility and additional diagnostic benefit of a high-resolution steady state 3D-volume interpolated breath-hold exam (VIBE) sequence between a continuous table movement (CTM) MR angiography of the entire runoff vasculature and a time-resolved (TWIST) MRA of the calves. METHODS: In this retrospective IRB approved study 224 patients (72 women, 152 men, mean age 67.29 ± 13.9) were included who had undergone a low-dose MR angiographic protocol at 3T (Siemens TimTrio) after injection of 0.1 mmol/kg gadobutrol including a CTM MRA, a time-resolved MRA of the calf station and a steady state 3D VIBE sequence prior to the time-resolved MRA. One board-certified radiologist rated the image quality of the steady state VIBE sequences on an ordinal three point scale (excellent, good, poor) and analyzed the images for additional diagnostic findings of and beyond the vascular system in comparison to the CTM MRA and the time-resolved MRA. Descriptive statistics and demographic patient data were used for further evaluation. RESULTS: The image quality of the steady state imaging of the pelvis, upper and lower leg was excellent in up to 88%, 84% and 47%, respectively, while poor image quality was only detected in the upper (2%) and lower leg (6%). An additional diagnostic benefit was found in 44% of the patients overall. The most common relevant pathologies included inflammatory processes of the soft tissues (26%), thrombi (14%), abscesses (13%) and tumors (11%). In subgroups of patients above the age of 60, 65, 70, 75 and 80 years an additional pathology was found in 50% 33%, 44%, 65% and 58%, respectively. There was no significant difference in terms of additional findings between men and women (46% and 39%, p > 0.05) and inpatients and outpatients (42% and 45%, p > 0.05). CONCLUSION: Steady state imaging is also feasible with extracellular contrast agents with good image quality yielding additional diagnostic findings in up to 44% and above in patients older than 60 years of age irrespective of gender or patient status. Given the short acquisition time of 4 minutes this sequence could be added to all peripheral MRA exams.
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Medios de Contraste , Extremidad Inferior/irrigación sanguínea , Angiografía por Resonancia Magnética , Compuestos Organometálicos , Pelvis/irrigación sanguínea , Enfermedad Arterial Periférica/diagnóstico , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Recognizing the causes of stillbirths and their associated conditions is essential to reduce its occurrence. OBJECTIVE: To describe information on stillbirths in Brazil during the past decade. SEARCH STRATEGY: A literature search was performed from January 2010 to December 2020. SELECTION CRITERIA: Original observational studies and clinical trials. DATA COLLECTION AND ANALYSIS: Data were manually extracted to a spreadsheet and descriptive analysis was performed. RESULTS: A total of 55 studies were included; 40 studies (72.2%) used the official data stored by national public health systems. Most articles aimed to estimate the rate and trends of stillbirth (60%) or their causes (55.4%). Among the 16 articles addressing the causes of death, 10 (62.5%) used the International Classification of Diseases; most of the articles only specified the main cause of death. Intrauterine hypoxia was the main cause reported (ranging from 14.3% to 54.9%). CONCLUSION: Having a national system based on compulsory notification of stillbirths may not be sufficient to provide quality information on occurrence and, especially, causes of death. Further improvements of the attribution and registration of causes of deaths and the implementation of educational actions for improving reporting systems are advisable. Finally, expanding the investigation of contributing factors associated with stillbirths would create an opportunity for further development of prevention strategies in low- and middle-income countries such as Brazil.
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Mortinato , Embarazo , Femenino , Humanos , Mortinato/epidemiología , Brasil/epidemiología , Causalidad , Causas de MuerteRESUMEN
INTRODUCTION: Recent studies reported decreased incidence of late onset sepsis in the neonatal intensive care unit (NICU), but it is unclear whether this is also true for late onset meningitis. Recent reports that both meningitis and intraventricular hemorrhage (IVH) are associated with systemic inflammation also raise questions about an association between the 2. METHODS: All preterm infants <33 weeks gestational age admitted to CNN NICUs from 2010 to 2018 were included. We compared incidence trends of late onset culture positive bloodstream infection (CPBSI) and late onset meningitis, and examined the association of meningitis and IVH (exposure), after adjustment for potential confounders. RESULTS: Of 36,573 infants included, 32,198 had no infection, 3,977 had only late onset CPBSI and 398 had late onset meningitis. There was significant decrease in incidence of late onset CPBSI (14%-10%; adjusted odds ratio (AOR) = 0.93; 95% confidence interval [CI] 0.92, 0.95) but not late onset meningitis (1.6%-1.2%; AOR = 0.98; 95% CI 0.94, 1.01). Compared to infants with no IVH grade 3 or above, infants with IVH grade 3, or above had higher odds of late onset meningitis versus no infection (AOR 4.16; 95% CI 3.17, 5.44), and higher odds of late onset meningitis versus late onset CPBSI (AOR 4.11; 95% CI 3.08, 5.50). CONCLUSIONS: There was a decreasing trend of late onset CPBSI but not late onset meningitis. An association between late onset meningitis and IVH grade 3 or above was observed. Late onset CPBSI and meningitis may have different risk factors and require different prevention strategies.
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Enfermedades del Prematuro , Meningitis , Sepsis , Canadá/epidemiología , Hemorragia Cerebral/epidemiología , Femenino , Edad Gestacional , Humanos , Incidencia , Lactante , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/epidemiología , Unidades de Cuidado Intensivo Neonatal , Meningitis/epidemiología , Embarazo , Estudios Retrospectivos , Sepsis/epidemiologíaRESUMEN
BACKGROUND: Between 7-35% of the maternity population are obese in high income countries and 1-40% in lower or middle-income countries. Women with obesity are traditionally limited by the choices available to them during pregnancy and birth because of the higher risk of complications. This evidence synthesis set out to summarise how women with obesity's perceptions of pregnancy and birth risk influence the care choices that they make. METHODS: A search of medical and health databases for qualitative studies written in the English language, published Jan 1993-April 2019 and reporting on pregnant women with obesity's perception of risk and influence of pregnancy and birth choices. Data was extracted by two reviewers onto a questions framework and then analysed using a thematic synthesis technique. Confidence in the qualitative findings was assessed using GRADE-CERQual. RESULTS: 23 full texts were included. The common themes on perception of risk were: 'Self-blame arising from others' stereotyped beliefs ', 'Normalisation', 'Lack of preparation', 'Fearful acceptance and inevitability' and 'Baby prioritised over mother'. For influence of choices, the themes were: 'External influences from personal stresses', 'Restrictive guidelines', 'Relationship with healthcare professional' and 'Perception of Risk'. CONCLUSIONS: Evidence on what influences women with obesity's pregnancy choices is limited. Further research is needed on the best methods to discuss the risks of pregnancy and birth for women with obesity in a sensitive and acceptable manner and to identify the key influences when women with obesity make choices antenatally and for birth planning.
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Madres , Obesidad/epidemiología , Complicaciones del Embarazo/epidemiología , Mujeres Embarazadas , Adulto , Femenino , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud , Humanos , Recién Nacido , Obesidad/complicaciones , Obesidad/fisiopatología , Embarazo , Complicaciones del Embarazo/fisiopatología , Factores de RiesgoRESUMEN
BACKGROUND: Continuous positive airway pressure (CPAP) ventilation may be used as a potential bridge to invasive mechanical ventilation (IMV), or as a ceiling-of-care for persistent hypoxaemia despite standard oxygen therapy, according to UK guidelines. We examined the association of mode of respiratory support and ceiling-of-care on mortality. METHODS: We conducted a retrospective cohort analysis of routinely collected de-identified data of adults with nasal/throat SARs-CoV-2 swab-positive results, at the Calderdale and Huddersfield NHS Foundation Trust between 10th March-19th April 2020 (outcomes determined on 22nd May). FINDINGS: Of 347 patients with SARs-CoV-2 swab-positive results, 294 (84.7%) patients admitted for Covid-19 were included in the study. Sixty-nine patients were trialled on CPAP, mostly delivered by face mask, either as an early ceiling of care instituted within 24 hours of admission (N = 19), or as a potential bridge to IMV (N = 44). Patients receiving a ceiling of care more than 24 hours after admission (N = 6) were excluded from the analysis. Two hundred and fifteen patients (73.1%) maximally received air/standard oxygen therapy, and 45 (15.3%) patients maximally received CPAP. Thirty-four patients (11.6%) required IMV, of which 24 had received prior CPAP. There were 138 patients with an early ceiling-of-care plan (pre-admission/within 24h). Overall, 103(35.0%) patients died and 191(65.0%) were alive at study end. Among all patients trialled on CPAP either as a potential bridge to IMV (N = 44) or as a ceiling-of-care (N = 19) mortality was 25% and 84%, respectively. Overall, there was strong evidence for higher mortality among patients who required CPAP or IMV, compared to those who required only air/oxygen (aOR 5.24 95%CI: 1.38, 19.81 and aOR 46.47 95%CI: 7.52, 287.08, respectively; p<0.001), and among patients with early ceiling-of-care compared to those without a ceiling (aOR 41.81 95%CI: 8.28, 211.17; p<0.001). Among patients without a ceiling of care (N = 137), 10 patients required prompt intubation following failed oxygen therapy, but 44 patients received CPAP. CPAP failure, defined as death (N = 1) or intubation (N = 24), occurred in 57% (N = 25) of patients. But in total, 75% (N = 33) of those started on CPAP with no ceiling of care recovered to discharge-19 without the need for IMV, and 14 following IMV. CONCLUSION: Our data suggest that among patients with no ceiling-of-care, an initial trial of CPAP as a potential bridge to IMV offers a favourable therapeutic alternative to early intubation. In contrast, among patients with a ceiling-of care, CPAP seems to offer little additional survival benefit beyond oxygen therapy alone. Information on ceilings of respiratory support is vital to interpreting mortality from Covid-19. STRENGTHS AND LIMITATIONS OF THIS STUDY: Sample size relatively small.Study sample representative of hospitalised Covid-19 patients in UK.Previously unreported data on role of ceilings-of-care in hospitalised Covid-19 patients.Novel data on use of CPAP separated by indication.
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COVID-19 , Presión de las Vías Aéreas Positiva Contínua/economía , Hospitalización/economía , Oxígeno/administración & dosificación , SARS-CoV-2 , Adulto , COVID-19/economía , COVID-19/epidemiología , COVID-19/terapia , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Acute pancreatitis in pregnancy is rare and can be caused by hypertriglyceridaemia. The management of hypertriglyceridaemia in pregnancy is complex and challenging as many lipid-lowering medications have been found to be unsafe in pregnancy. Patients who present with hypertriglyceridaemia commonly have multiple risk factors such as, diabetes, alcohol excess and hypothyroidism which pose a greater challenge to the management of these patients. We present a case of a 31-year-old woman presenting with familial hypertriglyceridaemia and type 2 diabetes mellitus in her third pregnancy. She had an uneventful pregnancy with the use of omega-3 fatty acids nutritional support, low-fat diet and tight glucose control with insulin and metformin.
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Diabetes Mellitus Tipo 2/terapia , Dieta con Restricción de Grasas , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Hiperlipoproteinemia Tipo IV/terapia , Pancreatitis/prevención & control , Adulto , Diabetes Mellitus Tipo 2/complicaciones , Combinación de Medicamentos , Femenino , Humanos , Hiperlipoproteinemia Tipo IV/complicaciones , Embarazo , Complicaciones del Embarazo/tratamiento farmacológico , Resultado del Embarazo , Triglicéridos/sangreRESUMEN
INTRODUCTION: This retrospective study investigated the clinical etiology of community-acquired bacteremic Klebsiella pneumoniae infections, and characterized laboratory and genetic markers which may be associated with primary liver abscess (PLA). METHODS: Community-onset K. pneumoniae bacteremic episodes from 2010 to 2011 were identified from the laboratory information system. Isolates were retrieved for susceptibility testing, hypermucoviscosity testing, PCR-based serotyping (K1, K2 and K5) and PCR detection of virulence genes (rmpA, alls, kfu and aerobactin). Clinical data collected from electronic medical records included primary and secondary diagnoses, co-existing morbidities, antibiotic therapy, and in-patient mortality. RESULTS: 129 bacteremic episodes were identified. The most common primary infections were pneumonia (n = 24, 18.6%), primary liver abscess (n = 21, 16.3%) and urinary tract infections (n = 21, 16.3%). Hypermucoviscosity was present in 55 isolates (42.6%). The most commonly detected virulence genes were aerobactin (n = 63, 48.8%) and rmpA (n = 59, 45.7%). Isolates causing liver abscess were significantly associated with a positive string test, rmpA, aerobactin gene, and capsular serotype K1 (all p < 0.01), but not with capsular serotype K2, K5, kfu, or allS genes. The absence of a positive string test, rmpA, or aerobactin genes had a 97.3%-100% negative predictive value for PLA. The positive predictive values of the string test, rmpA, aerobactin genes, and serotype K1 for PLA ranged from 31.7% to 35.6%. CONCLUSION: In our study population, pneumonia and PLA were the most common sources of community-acquired bacteremia. Hypermucoviscosity, rmpA, aerobactin, and serotype K1 could be useful laboratory markers to alert clinicians to arrange abdominal imaging to detect liver abscess.
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Bacteriemia/microbiología , Cápsulas Bacterianas/genética , Proteínas Bacterianas/genética , Ácidos Hidroxámicos , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/patogenicidad , Absceso Hepático/microbiología , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Humanos , Ácidos Hidroxámicos/metabolismo , Klebsiella pneumoniae/clasificación , Klebsiella pneumoniae/genética , Reacción en Cadena de la Polimerasa , Estudios Retrospectivos , Serogrupo , Serotipificación , Singapur , Factores de Virulencia/genéticaRESUMEN
PURPOSE: The purpose of this study was to prospectively evaluate the feasibility of detecting calcified aortic plaques in apolipoprotein E knockout (ApoE-KO) mice using a state-of-the-art human computed tomography (CT) system. MATERIALS AND METHODS: Eleven ApoE-KO and 9 wild-type mice, all male, were examined in this study. After intraperitoneal injection of 6.6% ketamine all mice underwent 2 ultra-high-resolution CT protocols on a third-generation dual-source CT system at 120 kVp and 130 kVp tube voltage, both performed with a tube current time product of 1300 mAs. Images (0.4 mm) with an increment of 0.2 mm were reconstructed using an iterative reconstruction algorithm. Calcium detectability and scores (Agatston, volume, mass) were determined with a dedicated human calcium scoring software (CaScoring). After the CT examination, a calcium quantification assay of the aortae was performed to determine the aortic calcium content of each mouse. The CT scan time ranged between 40 and 48 seconds. All mice survived the procedure. RESULTS: Calcified plaques could be detected in 8 of 11 ApoE-KO mice. Quantification of calcium levels showed significant differences between those with morphologic calcium plaques detected in CT and those without (3.44±1.6 µg Ca/mg vs. 0.33±0.35 µg Ca/mg; P<0.05). The receiver-operating characteristics analysis revealed a total calcium cut-off value of 0.71 µg Ca/mg for the detection using calcium score algorithms (specificity: 100% and sensitivity: 90%). CONCLUSION: Using a state-of-the-art human CT protocol and an in-human-established calcium scoring system allows for the detection and quantification of calcified aortic plaques in ApoE-KO mice. These results may facilitate preclinical imaging for translational and longitudinal atherosclerotic research studies.
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Apolipoproteínas E/deficiencia , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Placa Aterosclerótica/diagnóstico por imagen , Animales , Apolipoproteínas E/genética , Enfermedad de la Arteria Coronaria/genética , Modelos Animales de Enfermedad , Estudios de Factibilidad , Masculino , Ratones Endogámicos C57BL , Placa Aterosclerótica/genética , Estudios ProspectivosRESUMEN
AIM: The purpose of this IRB-approved, retrospective study was to compare image quality between 2D and high-resolution 3D, T2-weighted (T2WI) magnetic resonance imaging (MRI) sequences and to investigate the additional value of ultra-high b-value diffusion-weighted imaging (DWI; b=2,000 mm/s2) for both rectal cancer staging and evaluating treatment response. MATERIALS AND METHODS: From 12 February to 24 August 2016, 26 consecutive patients (22 males, four females; mean age: 61.9±14.0 years) with histologically-proven rectal cancer. In total 31 examinations [12 prior to and 19 after chemoradiation (CRT)] were included. The patients underwent pelvic MRI on a 3.0-T scanner (Magnetom Skyra, Erlangen, Germany). Three radiologists (3, 4, and 5 years of experience in MRI, respectively) independently assessed all images and rated the image quality of DWI (b=800 mm/s2), apparent diffusion coefficient map, DWI (b=2,000 mm/s2), 3D sagittal T2WI, 3D axial T2WI, 2D sagittal T2WI, and 2D axial T2WI of each patient, respectively. In addition, signal intensity ratios (SIR) were calculated between rectal cancer and obturator internus muscle (background) in all patients after CRT on DWI (b=2,000 mm/s2) and correlated with histopathological regression grade (RG). RESULTS: Tumor delineation was significantly better by 2D T2WI than 3D T2WI both before and after CRT (before CRT: Z=-3.2, p=0.02; after CRT: Z=-4.408, p<0.001; all: Z=-5.192; p<0.001) and was the preferred method, although image quality ratings were not significantly different (3D sagittal: 4.00±0.48; 2D sagittal: 4.03±0.34, p=0.713; 3D axial: 3.85±0.61, 2D axial: 3.78±0.64, p=0.537). Independent t-test showed significantly higher SIR between those with RG 1 or 2 (moderate response: mean score=2.02) and those with RG 3+4 (good response: mean score=0.8) (t=3.044, p=0.011). In those with RG 4 (complete response), SIR of b2000 was 0.946 compared to a 1.41 average of the whole cohort. In two patients, tumor was invisible on b2000 following CRT (RG 3 and 4, respectively). Interobserver agreement was mostly good (κ≥0.6) regarding image quality assessment, except for poor agreement (κ=0.4) in DWI (b2000) between the two less-experienced readers. CONCLUSION: In conclusion, 3D T2WI might be useful for evaluating response to neoadjuvant therapy in a comprehensive, cost-effective protocol, where 2D imaging seems to be preferable. In addition, DWI (b2000) may be beneficial in assessing both the primary and the residual tumor after CRT in rectal cancer and SIR may be helpful in assessing response to CRT.
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Adenocarcinoma/patología , Imagen de Difusión por Resonancia Magnética/métodos , Interpretación de Imagen Asistida por Computador/métodos , Imagenología Tridimensional/métodos , Garantía de la Calidad de Atención de Salud , Neoplasias del Recto/patología , Adenocarcinoma/terapia , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia Adyuvante , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Neoplasias del Recto/terapia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Recently, several studies reported increased signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted magnetic resonance imaging (MRI) as a possible consequence of multiple applications of gadolinium-based contrast agents. The aim of this study was to investigate with sodium (23 Na) MRI possible tissue abnormalities of the DN in multiple sclerosis (MS) patients. METHODS: Sodium and conventional MRI were performed on a clinical 3T scanner. Total sodium concentrations (TSCs) of the DN, as well as DN-to-pons and DN-to-cerebellum SI ratios on unenhanced T1-weighted MRI were calculated. RESULTS: A total of 18 subjects (6/18 normal controls, 12/18 MS patients [6/12 with T1 hyperintense DN]) were investigated. There was no significant difference of TSC values of the DN in MS patients with a T1-hyperintense DN (33.70 ± 2.14 mM) compared to MS patients without those signal abnormalities (33.29 ± 1.67 mM; P = .67) or to healthy controls (33.14 ± 1.12; P = .32). CONCLUSIONS: Normal sodium signal in the T1-hyperintense DN in MS patients may point to relative tissue integrity despite gadolinium deposition in this area.
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Núcleos Cerebelosos/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Adulto , Medios de Contraste , Femenino , Gadolinio , Humanos , Masculino , Persona de Mediana Edad , Puente/diagnóstico por imagen , Estudios Retrospectivos , SodioRESUMEN
To evaluate the feasibility and potential on therapy management of time-resolved dynamic computed tomography angiography (dCTA) in patients with forearm arterio-venous fistula (AVF)/arterio-venous grafts (AVG). Thirty-five patients with complex failing forearm AVF/AVGs were examined with ultrasound and a dCTA protocol. Diagnosis and therapy management was evaluated versus duplex ultrasound (DUS) in three different readouts: 1. all dCTA datasets; 2. one arterial phase of the dCTA dataset; 3. one arterial and one venous dataset out of the dCTA dataset. All reads were performed >30 days apart from each other. Using all data of the dCTA examination, 20 patients were classified as having a stenosis >50%, 12 high-shunt flow, 11 partial thrombosis, 5 venous aneurysms and 5 complete thrombosis of their AVF/AVG grafts. This lead to 13 additional pathologic findings not visible on DUS and reclassification as normal in one patient with suspected AVF stenosis and complete thrombus on DUS. These additional findings lead to a direct change of therapeutic management in 8 patients. Compared to readout 1 (53 pathologies), readout number 2 and 3 revealed only 33 and 41 pathologies, respectively. dCTA provides additional information, improving diagnostic confidence and leading to changes in therapy management when compared to DUS alone.
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Fístula Arteriovenosa/diagnóstico por imagen , Angiografía por Tomografía Computarizada/métodos , Antebrazo/diagnóstico por imagen , Fallo Renal Crónico/diagnóstico por imagen , Adulto , Anciano , Aneurisma/diagnóstico por imagen , Aneurisma/fisiopatología , Fístula Arteriovenosa/fisiopatología , Derivación Arteriovenosa Quirúrgica , Femenino , Antebrazo/patología , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Diálisis Renal , Trombosis/diagnóstico por imagen , Trombosis/fisiopatología , Ultrasonografía Doppler DúplexRESUMEN
PURPOSE: Dynamic [18 F]fluoro-ethyl-L-tyrosine positron emission tomography ([18 F]FET-PET) is used to identify tumor lesions for radiotherapy treatment planning, to differentiate glioma recurrence from radiation necrosis and to classify gliomas grading. To segment different regions in the brain k-means cluster analysis can be used. The main disadvantage of k-means is that the number of clusters must be pre-defined. In this study, we therefore compared different cluster validity indices for automated and reproducible determination of the optimal number of clusters based on the dynamic PET data. METHODS: The k-means algorithm was applied to dynamic [18 F]FET-PET images of 8 patients. Akaike information criterion (AIC), WB, I, modified Dunn's and Silhouette indices were compared on their ability to determine the optimal number of clusters based on requirements for an adequate cluster validity index. To check the reproducibility of k-means, the coefficients of variation CVs of the objective function values OFVs (sum of squared Euclidean distances within each cluster) were calculated using 100 random centroid initialization replications RCI100 for 2 to 50 clusters. k-means was performed independently on three neighboring slices containing tumor for each patient to investigate the stability of the optimal number of clusters within them. To check the independence of the validity indices on the number of voxels, cluster analysis was applied after duplication of a slice selected from each patient. CVs of index values were calculated at the optimal number of clusters using RCI100 to investigate the reproducibility of the validity indices. To check if the indices have a single extremum, visual inspection was performed on the replication with minimum OFV from RCI100 . RESULTS: The maximum CV of OFVs was 2.7 × 10-2 from all patients. The optimal number of clusters given by modified Dunn's and Silhouette indices was 2 or 3 leading to a very poor segmentation. WB and I indices suggested in median 5, [range 4-6] and 4, [range 3-6] clusters, respectively. For WB, I, modified Dunn's and Silhouette validity indices the suggested optimal number of clusters was not affected by the number of the voxels. The maximum coefficient of variation of WB, I, modified Dunn's, and Silhouette validity indices were 3 × 10-2 , 1, 2 × 10-1 and 3 × 10-3 , respectively. WB-index showed a single global maximum, whereas the other indices showed also local extrema. CONCLUSION: From the investigated cluster validity indices, the WB-index is best suited for automated determination of the optimal number of clusters for [18 F]FET-PET brain images for the investigated image reconstruction algorithm and the used scanner: it yields meaningful results allowing better differentiation of tissues with higher number of clusters, it is simple, reproducible and has an unique global minimum.
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Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Tomografía de Emisión de Positrones , Tirosina/análogos & derivados , Algoritmos , Diagnóstico Diferencial , Glioma/diagnóstico por imagen , Humanos , Recurrencia , Reproducibilidad de los ResultadosRESUMEN
RATIONALE AND OBJECTIVES: Despite ongoing technical refinements, coronary computed tomography angiography (cCTA) remains challenging in its diagnostic value by electrocardiographic (ECG) misregistration and motion artifacts, which commonly occur in patients with atrial fibrillation and high or irregular heart rates. The aim of this study was to evaluate the radiation dose and the number of inconclusive coronary segments at cCTA using retrospective ECG gating at 100 and 70 kV. MATERIALS AND METHODS: With institutional review board approval, 154 patients (median age 54 years, 98 men) with high or irregular heart rate prospectively underwent retrospectively ECG-gated cCTA without tube current modulation on a third-generation dual-source computed tomography (DSCT) system at 70 kV (n = 103) or on a second-generation DSCT system at 100 kV (n = 51). Images were reconstructed in best diastolic phase (BDP), best systolic phase (BSP), and in all phases (APs) at 10% intervals across the R-R cycle. Objective and subjective image qualities were evaluated as well as the presence of motion artifacts with the three different reconstruction approaches. RESULTS: The mean heart rate was 93 ± 16 bpm. The mean effective radiation dose was 4.5 mSv for 70 kV compared to 8.4 mSv for 100 kV (P < 0.05). At BDP reconstruction, 71% (n = 110) of the patients showed motion artifacts in one or more coronary segments. At BSP reconstruction, the number of patients with motion artifacts decreased to 37% (n = 57). In contrast, if images were reconstructed with the AP approach, all vessels and coronary segments were evaluable with both cCTA protocols. CONCLUSIONS: Retrospectively ECG-gated cCTA at 70 kV results in 52% decreased radiation dose. Further using the AP algorithm allowed for diagnostic evaluation of all coronary segments for stenosis, in contrast to BDP or BSP phase alone.
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Arritmias Cardíacas/diagnóstico por imagen , Angiografía por Tomografía Computarizada/normas , Angiografía Coronaria/normas , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Artefactos , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Electrocardiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dosis de Radiación , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Estudios Retrospectivos , Relación Señal-Ruido , Adulto JovenRESUMEN
AIM: To assess whether multiparametric MRI (mMRI) can serve as a tool for evaluating response to chemoradiation therapy (CRT) in advanced-stage rectal cancer. PATIENTS AND METHODS: Twenty-one patients underwent a mMRI protocol at 3T before and after CRT. Two experienced radiologists evaluated the MRI measurements and inter-reader correlation was assessed. Changes in functional parameters in relation to regression, as well as pT stage were analyzed. The perfusion parameters plasma flow (PF) and mean transit time (MTT) were calculated offline using the established UMM Perfusion tool. RESULTS: Apparent diffusion coefficient values were significantly different among the different tumor RGs before CRT (p=0.041). Changes of dynamic contrast enhanced (DCE) MRI values did not reflect treatment response (PF: p=0.5; MTT: p=0.74). CONCLUSION: The results of our study population indicate that a high initial apparent diffusion coefficient value may be predictive of response to therapy following CRT.