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BACKGROUND & AIMS: Agile scores, including liver stiffness measurements (LSM) and routine clinical/laboratory biomarkers, have been developed for advanced fibrosis (F≥3) and cirrhosis (F4), respectively, in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We independently validated the diagnostic accuracy of these scores in MASLD, alcohol-related liver disease (ALD) and chronic hepatitis B or C (CHB/C) and assessed them in clinical algorithms with FIB-4 and LSM. METHODS: We included 4,243 patients (MASLD: 912, ALD: 386, CHB: 597, CHC: 2,348) with LSM, liver biopsy and laboratory tests within 6 months. FIB-4, Agile 3+ and Agile 4 scores were calculated. RESULTS: For F≥3, the diagnostic accuracy of Agile 3+ and LSM were similar in MASLD (AUC: 0.86 vs. 0.86, p = 0.831) and ALD (0.92 vs. 0.94, p = 0.123). For cirrhosis, Agile 4 was similar to LSM in MASLD (0.89 vs. 0.90, p = 0.412) and ALD (0.94 vs. 0.95, p = 0.513). Agile 3+/4 performed worse than LSM in CHB/C. Using predefined dual thresholds of 90% sensitivity/specificity, correct classification rates in MASLD were 66% vs. 61% using Agile 3+ vs. LS dual cut-offs and 71% vs. 67% in ALD, respectively. When using Agile 3+ or LSM as a second step after FIB-4 >1.3, correct classification rates were higher with Agile 3+ than LSM, both for MASLD (75% vs. 71%) and ALD (76% vs. 72%), with fewer indeterminate results. Positive agreement of LSM and Agile 3+/4 significantly increased the specificity of a diagnosis of advanced fibrosis/cirrhosis. CONCLUSION: Agile 3+ and Agile 4 have equal diagnostic accuracy with LSM in both MASLD and ALD but result in fewer indeterminate results. Sequential use of FIB-4 and Agile 3+/4 or concurrent Agile 3+/4 and LSM can be used to further optimize F≥3 diagnosis. IMPACT AND IMPLICATIONS: As of today, it is accepted that there will be no single non-invasive test or an isolated cut-off for identifying patients with advanced chronic liver disease. Here, we confirmed that Agile 3+ and Agile 4 scores are useful alternatives to simple liver stiffness measurement in diagnosing advanced fibrosis/cirrhosis in steatotic liver disease, but they do not perform as well in chronic viral hepatitis. Agile scores can help optimize the diagnosis of advanced fibrosis/cirrhosis in a dual cut-off strategy by reducing the number of indeterminate results either alone or in a sequential strategy after FIB-4. The combination of Agile scores and liver stiffness measurement can further increase our confidence in a positive diagnosis of advanced fibrosis/cirrhosis. These novel combination strategies can be useful tools to predict the likelihood of advanced stages of liver disease with the highest possible accuracy in a secondary/tertiary healthcare setting.
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AIM: To investigate perceptions of informal caregivers of community-dwelling persons with dementia (PwD) regarding health and social care services and their correlates using the Behavioral Model of Healthcare Utilization as the theoretical framework. METHODS: This was a cross-sectional study using a purposive sampling technique to identify, through community-based health and social care services, caregivers of PwD. Face-to-face interviews were conducted with 118 informal caregivers (78.8% female, mean age = 58.9 years) via a structured questionnaire. RESULTS: Three 'Perceptions of Services' subscales were identified: 'Availability and Adequacy of Services' (AAS), 'Physicians' Competence' (COMP), and 'Professionals' Behavior' (PB). Predisposing factors (gender, employment, familism) and enabling/impeding factors (caregiving impedes work, quality of life aspects - environment and social relationships, information about dementia) were significant correlates of the AAS and COMP subscales. Familism was negatively associated with the AAS subscale. PwD's perceived declined physical and behavioral functioning was related to worse perceptions regarding professionals' behavior (PB) toward the PwD. CONCLUSION: Understanding the factors associated with caregivers' perceptions of health and social care community services may guide the development of interventions that facilitate the appropriate use of those services, provide increased support to PwD and their caregivers, and delay potential institutionalization.
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Cuidadores , Demencia , Estudios Transversales , Femenino , Grecia , Humanos , Masculino , Percepción , Calidad de VidaRESUMEN
BACKGROUND: The Baveno VI consensus proposed a dual liver stiffness (LS) by transient elastography threshold of <10 and >15 kPa for excluding and diagnosing compensated advanced chronic liver disease (cACLD) in the absence of other clinical signs. Herein, we aimed to validate these criteria in a real-world multicentre study. METHODS: We included 5,648 patients (mean age 51 ± 13 years, 53% males) from 10 European liver centres who had a liver biopsy and LS measurement within 6 months. We included patients with chronic hepatitis C (n = 2,913, 52%), non-alcoholic fatty liver disease (NAFLD, n = 1,073, 19%), alcohol-related liver disease (ALD, n = 946, 17%) or chronic hepatitis B (n = 716, 13%). cACLD was defined as fibrosis stage ≥F3. RESULTS: Overall, 3,606 (66%) and 987 (18%) patients had LS <10 and >15 kPa, respectively, while cACLD was histologically confirmed in 1,772 (31%) patients. The cut-offs of <10 and >15 kPa showed 75% sensitivity and 96% specificity to exclude and diagnose cACLD, respectively. Examining the ROC curve, a more optimal dual cut-off at <7 and >12 kPa, with 91% sensitivity and 92% specificity for excluding and diagnosing cACLD (AUC 0.87; 95% CI 0.86-0.88; p <0.001) was derived. Specifically, for ALD and NAFLD, a low cut-off of 8 kPa can be used (sensitivity=93%). For the unclassified patients, we derived a risk model based on common patient characteristics with better discrimination than LS alone (AUC 0.74 vs. 0.69; p <0.001). CONCLUSIONS: Instead of the Baveno VI proposed <10 and >15 kPa dual cut-offs, we found that the <8 kPa (or <7 kPa for viral hepatitis) and >12 kPa dual cut-offs have better diagnostic accuracy in cACLD. LAY SUMMARY: The term compensated advanced chronic liver disease (cACLD) was introduced in 2015 to describe the spectrum of advanced fibrosis and cirrhosis in asymptomatic patients. It was also suggested that cACLD could be diagnosed or ruled out based on specific liver stiffness values, which can be non-invasively measured by transient elastography. Herein, we assessed the suggested cut-off values and identified alternative values that offered better overall accuracy for diagnosing or ruling out cACLD.
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Diagnóstico por Imagen de Elasticidad , Hepatitis B Crónica , Hepatitis Alcohólica , Cirrosis Hepática , Hígado , Enfermedad del Hígado Graso no Alcohólico , Biopsia , Precisión de la Medición Dimensional , Elasticidad , Diagnóstico por Imagen de Elasticidad/métodos , Diagnóstico por Imagen de Elasticidad/normas , Diagnóstico por Imagen de Elasticidad/estadística & datos numéricos , Europa (Continente)/epidemiología , Femenino , Hepatitis B Crónica/complicaciones , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/patología , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/epidemiología , Hepatitis Alcohólica/patología , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/epidemiología , Cirrosis Hepática/etiología , Masculino , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Enfermedad del Hígado Graso no Alcohólico/patología , Gravedad del Paciente , Sensibilidad y EspecificidadRESUMEN
The present study evaluated the role of having plants at home during the confinement period as a result of the COVID-19 pandemic that deprived people of freely visiting open green spaces. Preferences concerning the quantity of the desired vegetation as well as the ways in which the COVID-19 crisis affected the change of perceptions with regard to having plants at home were also evaluated. A questionnaire, which was filled by 4205 participants, provided an undistracted evaluation of the impact of indoor and outdoor plants on their emotional welfare considering behavioural, social, and demographic variables. The emotional state of the respondents was neutral and a significant proportion expressed positive emotions. Having indoor plants was correlated with more positive emotions, and confined inhabitants allocated more time for plant maintenance. By contrast, negative emotions prevailed in respondents who related to a positive COVID-19 case, which was more frequent in females and young participants living in small houses that received low levels of natural light and had few or no plants. A few indoor plants placed in strategic positions were also preferred compared with a high number of plants. By contrast, an increased amount of vegetation accompanied by living walls was preferred for outdoor settings. Living walls were considered as advantageous for increasing indoor vegetation, but they were also associated with technical and economical hurdles.
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BACKGROUND: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated hydrolase that appears to have a protective action against atherosclerosis. The aim of our study is to identify whether PON-1 levels may be associated with the manifestation of symptoms in patients with carotid artery stenosis. METHODS: We studied all patients who underwent carotid endarterectomy in the Vascular Surgery Department of Laikon Hospital, Athens, Greece, from July 2012 to July 2014. Medical history was recorded and PON-1 glucose, total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglycerides levels were measured. Variables were compared between symptomatic and asymptomatic patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the accuracy of PON-1 to predict symptoms. RESULTS: A total of 74 patients were included, 41 were asymptomatic and the mean age was 68.5 years. The 2 groups appear to differ significantly with regards to the PON-1 levels, with the symptomatic group showing lower levels (5.3 ± 1.19 vs. 4.6 ± 1.36 ng/mL; P = 0.025). ROC analysis demonstrated an area under the curve of 0.654 (P = 0.023). CONCLUSIONS: Reduced PON-1 levels showed a significant association with symptomatic status, which was independent of other traditional cardiovascular factors. Further studies are required to prospectively assess the role of PON-1 in predicting cerebrovascular events in patients with carotid artery disease.
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Arildialquilfosfatasa/sangre , Estenosis Carotídea/sangre , Anciano , Enfermedades Asintomáticas , Biomarcadores/sangre , Glucemia/análisis , Estenosis Carotídea/complicaciones , Estenosis Carotídea/diagnóstico , Estenosis Carotídea/cirugía , Estudios Transversales , Regulación hacia Abajo , Endarterectomía Carotidea , Femenino , Humanos , Lípidos/sangre , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: In primary breast cancer metastases frequently arise from a state of dormancy that may persist for extended periods of time. We investigated the efficacy of plasma micro-RNA (miR)-21, miR-23b, miR-190, miR-200b and miR-200c, related to dormancy and metastasis, to predict the outcome of patients with early breast cancer. METHODS: miRNAs were evaluated by RT-qPCR in plasma obtained before adjuvant chemotherapy. miRNA expression, classified as high or low according to median values, correlated with relapse and survival. Receiver operating characteristic (ROC) curves were constructed to determine miRNA sensitivity and specificity. RESULTS: miR-21 (p < 0.001), miR-23b (p = 0.028) and miR-200c (p < 0.001) expression were higher and miR-190 was lower (p = 0.013) in relapsed (n = 49), compared to non-relapsed patients (n = 84). Interestingly, miR-190 was lower (p = 0.0032) in patients with early relapse (at < 3 years; n = 23) compared to those without early relapse (n = 110). On the other hand, miR-21 and miR-200c were higher (p = 0.015 and p < 0.001, respectively) in patients with late relapse (relapse at ≥ 5 years; n = 20) as compared to non-relapsed patients. High miR-200c was associated with shorter disease-free survival (DFS) (p = 0.005) and high miR-21 with both shorter DFS and overall survival (OS) (p < 0.001 and p = 0.033, respectively) compared to low expression. ROC curve analysis revealed that miR-21, miR-23b, miR-190 and miR-200c discriminated relapsed from non-relapsed patients. A combination of of miR-21, miR-23b and miR-190 showed higher sensitivity and specificity in ROC analyses compared to each miRNA alone; accuracy was further improved by adding lymph node infiltration and tumor grade to the panel of three miRs (AUC 0.873). Furthermore, the combination of miR-200c, lymph node infiltration, tumor grade and estrogen receptor predicted late relapse (AUC 0.890). CONCLUSIONS: Circulating miRNAs are differentially expressed among relapsed and non-relapsed patients with early breast cancer and predict recurrence many years before its clinical detection. Our results suggest that miRNAs represent potential circulating biomarkers in early breast cancer.
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Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , MicroARN Circulante/sangre , Recurrencia Local de Neoplasia/sangre , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , MicroARN Circulante/genética , Supervivencia sin Enfermedad , Detección Precoz del Cáncer , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Ganglios Linfáticos/patología , MicroARNs/genética , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patologíaRESUMEN
The aim of the present study was to explore the associations between visual outcomes of ocular injury patients in a tertiary hospital unit with clinical and demographic variables and to evaluate the psychosocial impact of the injury on the patients. An 18-month prospective study of 30 eye-injured adult patients was conducted in the General University Hospital of Heraklion, Crete, a tertiary referral hospital. All severe eye injury case information was prospectively collected between February 1, 2020 and August 31, 2021. Best corrected visual acuity (BCVA) was labelled not poor (>0.5/10 or >20/400 on the Snellen scale, <1.3 in LogMAR scale) and poor (≤0.5/10 or ≤20/400 on the Snellen scale, ≥1.3 on the LogMAR equivalent). Data regarding participants' perceived stress levels, by using Perceived Stress Scale 14 (PSS-14), were collected prospectively, one year after study end. Out of 30 ocular injury patients selected, 76.7% were men and most of them were self-employed and private or public sector workers (36.7%). Not poor final BCVA was related to not poor initial BCVA [odds ratio (OR) 1.714; P=0.006]. No statistical associations were found between visual outcome and demographic or clinical factors, but not poor final BCVA was associated with improved self-reported psychological condition of the sufferers, as examined by a questionnaire sheet developed to collect information for study purpose (8.36/10 vs. 6.40/10; P=0.011). No patient reported job loss or changed work status following the injury. Not poor initial BCVA was a significant predictor for not poor final visual outcomes (OR 1.714; P=0.006). Patients with not poor final BCVA expressed higher levels of positive psychology (8.36/10 vs. 6.40/10; P=0.011) and less fear of eye injury repetition (64.0 vs. 100.0%; P=0.286). Not poor final BCVA was associated with low PSS-14 scores one year after study end (77.3 vs. 0.0%, P=0.003). Collaboration between ophthalmologists, mental health professionals and primary care team may be important in order to help patients to cope with the psychosocial burden sequel to eye trauma.
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BACKGROUND: The role of metabolic/inflammatory hormonal systems in metabolic dysfunction associated steatotic liver disease (MASLD) remains to be fully elucidated. PURPOSE: To report the levels of the novel total and H-specific growth differentiation factor-15 (GDF-15) and other established hormonal systems and to describe hormonal patterns in controls and patients with MASLD and its stages. METHODS: This is a multicenter study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven MASLD (n = 374) and Controls (n = 81) were recruited. RESULTS: We report for the first time that total and H-specific GDF-15 levels are higher in MASLD, at-risk metabolic dysfunction associated steatohepatitis (MASH), and severe fibrosis than in Controls. In addition, follistatin-like-3 (FSTL-3), free insulin-like growth factor-1 (IGF-1), leptin, and insulin levels were higher in MASLD patients than in Controls, while adiponectin levels were lower in MASLD subjects than in Controls. Activin-A, follistatin (FST), FSTL-3, and insulin levels significantly increased in severe fibrosis compared to no/mild fibrosis, while free IGF-1 decreased. In addition, adiponectin levels were lower in subjects without fibrosis vs. any fibrosis. Moreover, GDF-15 presented a strong positive association for the likelihood of having MASLD and at-risk MASH, while in adjusted analyses, FST and adiponectin showed inverse associations. Two different patterns of at-risk MASH were revealed through unsupervised analysis (total variation explained=54%). The most frequent pattern met in our sample (34.3%) was characterized by higher levels of total and H-specific GDF-15, follistatins, and activins, as well as low adiponectin levels. The second pattern revealed was characterized by high levels of free IGF-1, insulin, and leptin, with low levels of activin-A and adiponectin. Similar patterns were also generated in the case of overall MASLD. CONCLUSIONS: Total and H-specific GDF-15 levels increase as MASLD severity progresses. FSTL-3, free IGF-1, leptin, and insulin are also higher, whereas adiponectin and activin-A levels are lower in the MASLD group than in Controls. Hormonal systems, including GDF-15, may not only be involved in the pathophysiology but could also prove useful for the diagnostic workup of MASLD and its stages and may potentially be of therapeutic value.
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Leptina , Enfermedad del Hígado Graso no Alcohólico , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Folistatina , Factor 15 de Diferenciación de Crecimiento , Adiponectina , Insulina , Activinas , Fibrosis , BiopsiaRESUMEN
AIMS: A new non-invasive tool (NIT) for non-alcoholic fatty liver disease (NAFLD) proposed in 2022 by the multi-ethnic Dallas Heart Study, i.e. the Dallas Steatosis Index (DSI), was validated herein using for the first time the gold standard i.e. liver biopsy-proven NAFLD. METHODS: This is a multicenter study based on samples and data from two Gastroenterology-Hepatology Clinics (Greece and Australia) and one Bariatric-Metabolic Surgery Clinic (Italy). Overall, n = 455 patients with biopsy-proven NAFLD (n = 374) and biopsy-proven controls (n = 81) were recruited. RESULTS: The ability of DSI to correctly classify participants as NAFLD or controls was very good, reaching an Area Under the Curve (AUC) = 0.887. The cut-off point that could best differentiate the presence vs. absence of NAFLD corresponded to DSI = 0.0 (risk threshold: 50% | Sensitivity: 0.88; Positive Predictive Value (PPV): 93.0%; F1-score = 0.91). DSI demonstrated significantly better performance characteristics than other liver steatosis indexes. Decision curve analysis revealed that the benefit of DSI as a marker to indicate the need for invasive liver assessment was confirmed only when higher DSI values, i.e. ≥ 1.4, were used as risk thresholds. DSI performance to differentiate disease progression was inadequate (all AUCs < 0.700). CONCLUSIONS: DSI is more useful for disease screening (NAFLD vs. controls) than to differentiate diseases stages or progression. The value of any inclusion of DSI to guidelines needs to be further studied.
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BACKGROUND: Non-invasive tools (NIT) for metabolic-dysfunction associated liver disease (MASLD) screening or diagnosis need to be thoroughly validated using liver biopsies. PURPOSE: To externally validate NITs designed to differentiate the presence or absence of liver steatosis as well as more advanced disease stages, to confirm fully validated indexes (n = 7 NITs), to fully validate partially validated indexes (n = 5 NITs), and to validate for the first time one new index (n = 1 NIT). METHODS: This is a multi-center study from two Gastroenterology-Hepatology Departments (Greece and Australia) and one Bariatric-Metabolic Surgery Department (Italy). Overall, n = 455 serum samples of patients with biopsy-proven MASLD (n = 374, including 237 patients with metabolic-dysfunction associated steatohepatitis (MASH)) and Controls (n = 81) were recruited. A complete validation analysis was performed to differentiate the presence of MASLD vs. Controls, MASH vs. metabolic-dysfunction associated steatotic liver (MASL), histological features of MASH, and fibrosis stages. RESULTS: The index of NASH (ION) demonstrated the highest differentiation ability for the presence of MASLD vs. Controls, with the area under the curve (AUC) being 0.894. For specific histological characterization of MASH, no NIT demonstrated adequate performance, while in the case of specific features of MASH, such as hepatocellular ballooning and lobular inflammation, ION demonstrated the best performance with AUC being close to or above 0.850. For fibrosis (F) classification, the highest AUC was reached by the aspartate aminotransferase to platelet ratio index (APRI) being ~0.850 yet only with the potential to differentiate the severe fibrosis stages (F3, F4) vs. mild or moderate fibrosis (F0-2) with an AUC > 0.900 in patients without T2DM. When we excluded patients with morbid obesity, the differentiation ability of APRI was improved, reaching AUC = 0.802 for differentiating the presence of fibrosis F2-4 vs. F0-1. The recommended by current guidelines index FIB-4 seemed to differentiate adequately between severe (i.e., F3-4) and mild or moderate fibrosis (F0-2) with an AUC = 0.820, yet this was not the case when FIB-4 was used to classify patients with fibrosis F2-4 vs. F0-1. Trying to improve the predictive value of all NITs, using Youden's methodology, to optimize the suggested cut-off points did not materially improve the results. CONCLUSIONS: The validation of currently available NITs using biopsy-proven samples provides new evidence for their ability to differentiate between specific disease stages, histological features, and, most importantly, fibrosis grading. The overall performance of the examined NITs needs to be further improved for applications in the clinic.
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Cirrosis Hepática , Enfermedad del Hígado Graso no Alcohólico , Humanos , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/patología , Pruebas de Función Hepática , Biopsia , Hígado/patología , Aspartato AminotransferasasRESUMEN
NMR spectroscopy has become an indispensable tool for the metabolic profiling of foods and food products. In the present protocol, we report an analytical approach based on liquid-state NMR for the determination of polar and nonpolar metabolites in some common liquid (wine, spirits, juice) and solid (cheese, coffee, honey) foods. Although the diversity of foods precludes the use of a single protocol, with small modifications, the proposed methodologies can be adapted to a broader range of foodstuffs.