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Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 182
Author(s):  
Annalisa Cespiati ◽  
Marica Meroni ◽  
Rosa Lombardi ◽  
Giovanna Oberti ◽  
Paola Dongiovanni ◽  
...  

Sarcopenia is defined as a loss of muscle strength, mass and function and it is a predictor of mortality. Sarcopenia is not only a geriatric disease, but it is related to several chronic conditions, including liver diseases in both its early and advanced stages. Despite the increasing number of studies exploring the role of sarcopenia in the early stages of chronic liver disease (CLD), its prevalence and the relationship between these two clinical entities are still controversial. Myosteatosis is characterized by fat accumulation in the muscles and it is related to advanced liver disease, although its role in the early stages is still under researched. Therefore, in this narrative review, we firstly aimed to evaluate the prevalence and the pathogenetic mechanisms underlying sarcopenia and myosteatosis in the early stage of CLD across different aetiologies (mainly non-alcoholic fatty liver disease, alcohol-related liver disease and viral hepatitis). Secondly, due to the increasing prevalence of sarcopenia worldwide, we aimed to revise the current and the future therapeutic approaches for the management of sarcopenia in CLD.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 440
Author(s):  
Clara Martori ◽  
Lidia Sanchez-Moral ◽  
Tony Paul ◽  
Juan Carlos Pardo ◽  
Albert Font ◽  
...  

Prostate cancer (PC) is the most common malignancy and the fifth cause of cancer death in men. The treatment for localized or locally advanced stages offers a high probability of cure. Even though the therapeutic landscape has significantly improved over the last decade, metastatic PC (mPC) still has a poor prognosis mainly due to the development of therapy resistance. In this context, the use of immunotherapy alone or in combination with other drugs has been explored in recent years. However, T-cell directed immune checkpoint inhibitors (ICIs) have shown limited activity with inconclusive results in mPC patients, most likely due to the highly immunosuppressive PC tumor microenvironment (TME). In this scenario, targeting macrophages, a highly abundant immunosuppressive cell type in the TME, could offer a new therapeutic strategy to improve immunotherapy efficacy. In this review, we summarize the growing field of macrophage-directed immunotherapies and discuss how these could be applied in the treatment of mPC, focusing on their combination with ICIs.


2022 ◽  
Author(s):  
Adel Boueiz ◽  
Zhonghui Xu ◽  
Yale Chang ◽  
Aria Masoomi ◽  
Andrew Gregory ◽  
...  

Background: The heterogeneous nature of COPD complicates the identification of the predictors of disease progression and consequently the development of effective therapies. We aimed to improve the prediction of disease progression in COPD by using machine learning and incorporating a rich dataset of phenotypic features. Methods: We included 4,496 smokers with available data from their enrollment and 5-year follow-up visits in the Genetic Epidemiology of COPD (COPDGene) study. We constructed supervised random forest models to predict 5-year progression in FEV1 from 46 baseline demographic, clinical, physiologic, and imaging features. Using cross-validation, we randomly partitioned participants into training and testing samples. We also validated the results in the COPDGene 10-year follow-up visit. Results: Predicting the change in FEV1 over time is more challenging than simply predicting the future absolute FEV1 level. Nevertheless, the area under the ROC curves for the prediction of subjects in the top quartile of observed disease progression was 0.70 in the 10-year follow-up data. The model performance accuracy was best for GOLD1-2 subjects and it was harder to achieve accurate prediction in advanced stages of the disease. Predictive variables differed in their relative importance as well as for the predictions by GOLD grade. Conclusion: This state-of-the art approach along with deep phenotyping predicts FEV1 progression with reasonable accuracy. There is significant room for improvement in future models. This prediction model facilitates the identification of smokers at increased risk for rapid disease progression. Such findings may be useful in the selection of patient populations for targeted clinical trials.


Antioxidants ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 139
Author(s):  
Paola Montes ◽  
Ana Guerra-Librero ◽  
Paloma García ◽  
María Elena Cornejo-Calvo ◽  
María del Señor López ◽  
...  

This study focused on the impact of the treatment with the hypomethylating agent 5-azacitidine on the redox status and inflammation in 24 MDS patients. Clinical and genetic features of MDS patients were recorded, and peripheral blood samples were used to determine the activity of the endogenous antioxidant defense system (superoxide dismutase, SOD; catalase, CAT; glutathion peroxidase, GPx; and reductase, GRd, activities), markers of oxidative damage (lipid peroxidation, LPO, and advanced oxidation protein products, AOPP). Moreover, pro-inflammatory cytokines and plasma nitrite plus nitrate levels as markers of inflammation, as well as CoQ10 plasma levels, were also measured. Globally, MDS patients showed less redox status in terms of a reduction in the GSSG/GSH ratio and in the LPO levels, as well as increased CAT activity compared with healthy subjects, with no changes in SOD, GPx, and GRd activities, or AOPP levels. When analyzing the evolution from early to advanced stages of the disease, we found that the GPx activity, GSSG/GSH ratio, LPO, and AOPP increased, with a reduction in CAT. GPx changes were related to the presence of risk factors such as high-risk IPSS-R or mutational score. Moreover, there was an increase in IL-2, IL-6, IL-8, and TNF-α plasma levels, with a further increase of IL-2 and IL-10 from early to advanced stages of the disease. However, we did not observe any association between inflammation and oxidative stress. Finally, 5-azacitidine treatment generated oxidative stress in MDS patients, without affecting inflammation levels, suggesting that oxidative status and inflammation are two independent processes.


2022 ◽  
Vol 11 ◽  
pp. 1-4
Author(s):  
Luisa Albanese ◽  
Gemma Caliendo ◽  
Giovanna D'Elia ◽  
Luana Passariello ◽  
Anna Maria Molinari ◽  
...  

Our data confirm that intact fibroblast growth factor 23 (iFGF-23) concentration is increased in patients with chronic kidney disease (CKD) and that it increases with disease progression (stages I-V). Therefore, iFGF-23 could be considered an early biomarker in the course of chronic kidney disease-mineral bone disorder (CKD-MBD), which has several aspects that make it potentially useful in clinical practice. The availability of an automated method for iFGF-23 assay may represent an added value in the management of the patient with CKD-MBD already from the early stages of the disease, before the increase of the routinely used laboratory parameters, 1-84 parathyroid hormone (PTH) and 25-OH-vitamin D (25-OH-vitD), which occur in more advanced stages of the disease.


Author(s):  
P. Jagan Mohan Rao ◽  
N. Sandhyakishore ◽  
S. Sandeep ◽  
G. Neelima ◽  
A. Saritha ◽  
...  

Background: The genotype × environment interaction greatly influences the success of breeding and in multi-location trials complicates the identification of superior genotypes for a single location, due to magnitude of genotype by location interaction are often greater than genotype by year interaction. This necessitates genotype evaluation in multi environments trials in the advanced stages of selection. Methods: Nine elite pigeonpea genotypes of mid-early duration were evaluated in six diverse locations in randomized complete block design with three replications during kharif, 2019 to ascertain the stable genotypes, environments discrimination and genotype by environment crossovers using AMMI and GGE biplot stability models. Result: The results in the present investigation revealed that first two principal components explained 73.4% of variation interaction, while, 80.50% in GGE biplot. Both the models identified WRGE-126 (G6) as stable performer with high yield (1733 kg ha-1) and among the locations Tandur (E1) measured as the ideal environment. Whereas, the environments, Adilabad (E3) and Warangal (E4) were observed representative with better discriminating ability.


2022 ◽  
Vol 100 (S267) ◽  
Author(s):  
Vladislav Kotelin ◽  
Sergey Petrov ◽  
Marina Zueva ◽  
Anastasiya Zhuravleva ◽  
Irina Tsapenko

2021 ◽  
Vol 14 (4) ◽  
pp. 60-64
Author(s):  
V. V. Neroev ◽  
V. V. Gar’kavenko ◽  
V. V. Salmin

Purpose: to evaluate hypoxic changes in the limbus area conjunctiva of patients with primary open-angle glaucoma (POAG) treated with prolonged instillations of prostaglandin (PG) analogs. Material and methods. A spectrofluorimetric study of the limbus zone was carried out in 202 patients aged 56–87 years with POAG in the developed and advanced stages, divided into 2 groups. Group 1 consisted of patients aged 69.4 ± 10.3 years who received beta-blockers (BB) and carbonic anhydrase inhibitors (ICA) for 5–10 months; of these, 39 (30.2 %) had a developed stage of POAG and 90 (69.7 %) had advanced POAG. Group 2, aged 72.3 ± 9.4, received PG analogs, in addition to BB and ICA, for 5–10 months. In this group, 21 (28.7 %) patients had developed POAG and 52 (71.23 %) had advanced POAG. Results. The patients who received PG instillations showed a significantly higher ratio of fluorescence intensity in the wavelength range of 410/520 nm NADH/FAD (0.352 ± 0.043) than those receiving no such therapy (0.319 ± 0.047), which can be interpreted as a hypoxic state of the limbus area. Conclusion. Spectrofluorimetric testing of POAG patients taking PG analogs can be useful for detecting ischemia in the limbus area, because this category of patients are very likely to form cicatricial changes in the area of the filtration cushion in the early postoperative period after antiglaucomatous interventions.


Author(s):  
Loretta Ferrera ◽  
Floriana Cappiello ◽  
Maria Rosa Loffredo ◽  
Elena Puglisi ◽  
Bruno Casciaro ◽  
...  

AbstractMutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein lead to persistent lung bacterial infections, mainly due to Pseudomonas aeruginosa, causing loss of respiratory function and finally death of people affected by CF. Unfortunately, even in the era of CFTR modulation therapies, management of pulmonary infections in CF remains highly challenging especially for patients with advanced stages of lung disease. Recently, we identified antimicrobial peptides (AMPs), namely Esc peptides, with potent antipseudomonal activity. In this study, by means of electrophysiological techniques and computational studies we discovered their ability to increase the CFTR-controlled ion currents, by direct interaction with the F508del-CFTR mutant. Remarkably, this property was not explored previously with any AMPs or peptides in general. More interestingly, in contrast with clinically used CFTR modulators, Esc peptides would give particular benefit to CF patients by combining their capability to eradicate lung infections and to act as promoters of airway wound repair with their ability to ameliorate the activity of the channel with conductance defects. Overall, our findings not only highlighted Esc peptides as the first characterized AMPs with a novel property, that is the potentiator activity of CFTR, but also paved the avenue to investigate the functions of AMPs and/or other peptide molecules, for a new up-and-coming pharmacological approach to address CF lung disease.


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