BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to deco...BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.展开更多
Inorganic phosphate(Pi) is an essential nutrient to living organisms. It is required as a component of the energy metabolism,kinase/phosphatase signaling and in the formation and function of lipids,carbohydrates and n...Inorganic phosphate(Pi) is an essential nutrient to living organisms. It is required as a component of the energy metabolism,kinase/phosphatase signaling and in the formation and function of lipids,carbohydrates and nucleic acids and,at systemic level,it plays a key role for normal skeletal and dentin mineralization. Pi represents an abundant dietary element and its intestinal absorption is efficient,minimally regulated and typically extends to approximately 70%. Maintenance of proper Pi homeostasis is a critical event and serum Pi level is maintained within a narrow range through an elaborate network of humoral interactions and feedback loops involving intestine,kidney,parathyroid gland and bone,and depends on the activity of a number of hormones,including parathyroid hormone,1,25-dihydroxy vitamin D,and fibroblast growth factor 23 as major regulators of Pi homeostasis. Notably,Pi intake seemingly continues to increase as a consequence of chronic high-phosphorus(P) diets deriving from the growing consumption of highly processed foods,especially restaurant meals,fast foods,and convenience foods. Several recent reports have generated significant associations between high-P intake or high-serum Pi concentration and morbidity and mortality. Many chronic diseases,including cardiovascular diseases,obesity and even cancer have been proposed to be associated with high-P intakes and high-serum Pi concentrations. On the other hand,there is also evidence that Pi can have antiproliferative effects on some cancer cell types,depending on cell status and genetic background and achieve additive cytotoxic effects when combined with doxorubicin,illustrating its potential for clinical applications and suggesting that up-regulating Pi levels at local sites for brief times,might contribute to the development of novel and cheap modalities for therapeutic intervention in some tumours. Overall,the influence of Pi on cell function and the possible relationship to cancer have to be fully understood and investigated further.展开更多
The latest scientific knowledge has provided additional insights accountable for the worst prognosis for pancreatic ductal adenocarcinoma(PDAC).Among the causative factors,the aptitude to develop resistance towards ap...The latest scientific knowledge has provided additional insights accountable for the worst prognosis for pancreatic ductal adenocarcinoma(PDAC).Among the causative factors,the aptitude to develop resistance towards approved medications denotes the master key for understanding the lack of improvement in PDAC survival over the years.Even though several compounds have achieved encouraging results at preclinical stage,no new adjuvant agents have reached the bedside of PDAC patients lately.The adiponectin receptor agonist AdipoRon is emerging as a promising anticancer drug in different cancer models,particularly in PDAC.Building on the existing findings,we recently reinforced its candidacy in PDAC cells,proposing AdipoRon either as a suitable partner in gemcitabinebased treatment or as an effective drug in resistant cells.Crossing the current state-of-the-art,herein we provide a critical perspective on AdipoRon to figure out whether this receptor agonist can potentially be considered a future therapeutic choice in overcoming chemotherapy-induced resistance,expressly in PDAC.展开更多
文摘BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic event.Based on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),respectively.Clinically Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these patients.However,due to its invasiveness and costs,CSPH is almost never evaluated in clinical practice.Therefore,recognizing noninvasively predicting tools still have more appeal across healthcare systems.The red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been explored.AIM In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD patients.METHODS Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 years.At baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were collected.During FUP,DEs(timing and modaities)were recorded.CSPH was assessed at the baseline and on DE occurrence according to the available Clinical Practice Guidelines.RESULTS Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve analysis revealed RPR>0.472 and>0.894 as the best cut-offs in the prediction respectively of 3-year first DE,as well as its superiority compared to the other non-invasive tools examined.RPR(P:0.02)and the presence of baseline-CSPH(P:0.04)were significantly and independently associated with the DE.Patients presenting baseline-CSPH and RPR>0.472 showed higher risk of decompensation(P:0.0023).CONCLUSION Altogether these findings suggest the RPR as a valid and potentially applicable non-invasive tool in the prediction of timing and modalities of decompensation in MASLD-related cACLD patients.
文摘Inorganic phosphate(Pi) is an essential nutrient to living organisms. It is required as a component of the energy metabolism,kinase/phosphatase signaling and in the formation and function of lipids,carbohydrates and nucleic acids and,at systemic level,it plays a key role for normal skeletal and dentin mineralization. Pi represents an abundant dietary element and its intestinal absorption is efficient,minimally regulated and typically extends to approximately 70%. Maintenance of proper Pi homeostasis is a critical event and serum Pi level is maintained within a narrow range through an elaborate network of humoral interactions and feedback loops involving intestine,kidney,parathyroid gland and bone,and depends on the activity of a number of hormones,including parathyroid hormone,1,25-dihydroxy vitamin D,and fibroblast growth factor 23 as major regulators of Pi homeostasis. Notably,Pi intake seemingly continues to increase as a consequence of chronic high-phosphorus(P) diets deriving from the growing consumption of highly processed foods,especially restaurant meals,fast foods,and convenience foods. Several recent reports have generated significant associations between high-P intake or high-serum Pi concentration and morbidity and mortality. Many chronic diseases,including cardiovascular diseases,obesity and even cancer have been proposed to be associated with high-P intakes and high-serum Pi concentrations. On the other hand,there is also evidence that Pi can have antiproliferative effects on some cancer cell types,depending on cell status and genetic background and achieve additive cytotoxic effects when combined with doxorubicin,illustrating its potential for clinical applications and suggesting that up-regulating Pi levels at local sites for brief times,might contribute to the development of novel and cheap modalities for therapeutic intervention in some tumours. Overall,the influence of Pi on cell function and the possible relationship to cancer have to be fully understood and investigated further.
文摘The latest scientific knowledge has provided additional insights accountable for the worst prognosis for pancreatic ductal adenocarcinoma(PDAC).Among the causative factors,the aptitude to develop resistance towards approved medications denotes the master key for understanding the lack of improvement in PDAC survival over the years.Even though several compounds have achieved encouraging results at preclinical stage,no new adjuvant agents have reached the bedside of PDAC patients lately.The adiponectin receptor agonist AdipoRon is emerging as a promising anticancer drug in different cancer models,particularly in PDAC.Building on the existing findings,we recently reinforced its candidacy in PDAC cells,proposing AdipoRon either as a suitable partner in gemcitabinebased treatment or as an effective drug in resistant cells.Crossing the current state-of-the-art,herein we provide a critical perspective on AdipoRon to figure out whether this receptor agonist can potentially be considered a future therapeutic choice in overcoming chemotherapy-induced resistance,expressly in PDAC.
