Background and Aims: Circulating albumin in cirrhosis can be dysfunctional because of accumulating structural damages, leading to the concept of effective albumin concentration (eAlb), referring to the albumin portion presenting structural and functional integrity. We aimed to estimate eAlb in patients with decompensated cirrhosis and analyze its relationships with albumin function and clinical outcomes as compared to total albumin concentration (tAlb). Approach and Results: We evaluated 319 patients with cirrhosis hospitalized for acute decompensation (AD) with and without acute‐on‐chronic liver failure (ACLF) and 18 age‐ and sex‐comparable outpatients with compensated cirrhosis. tAlb was quantified by standard assay, whereas eAlb was estimated combining liquid chromatography/electrospray ionization/mass spectrometry and standard methods. Albumin binding and detoxification efficiency were evaluated by electron paramagnetic resonance analysis. Circulating albumin in patients with decompensated cirrhosis displayed multiple structural abnormalities, with reversible oxidation and glycation being the most frequent. As a result, eAlb progressively declined with the worsening of cirrhosis and was superior to tAlb in stratifying patients between compensated cirrhosis, AD, and ACLF, as well as patients with and without complications. Moreover, eAlb, but not tAlb, was closely associated with binding capacities in ACLF. Finally, eAlb at admission predicted the occurrence of ACLF within 30 days and mortality at 90 days better than tAlb. Conclusions: This large, observational study provides the evidence in patients with decompensated cirrhosis that eAlb can be quantified and differentiated from tAlb routinely measured in clinical practice. As compared to tAlb, eAlb is more closely associated with disease severity and albumin dysfunction and carries a greater prognostic power. These results prompt future research assessing eAlb as a biomarker for predicting prognosis and treatment response.
The aim of this review is to provide an overview of genitourinary health in peri- and postmenopause, particularly of vulvovaginal atrophy (VVA), which is part of genitourinary syndrome (GSM). This condition has a high prevalence among post-menopausal women and negatively affects a woman’s quality of life. Epidemiology, signs, symptoms, diagnostic criteria of VVA and target treatments for restoring vaginal health are discussed in light of the most recent literature. Issues related to this condition in menopausal women are under-diagnosed, lack objective diagnostic criteria, and consequently under-treated. Over the years, many treatments have been developed but their long-term effectiveness and safety have yet to be clearly defined. Patients are often dissatisfied and stop treatment, suggesting the need for a more personalized and tailored approach to achieve better compliance and thereby effectiveness. The aim of this paper is to provide an overview of the most recent literature on VVA in order to help the gynecologist in the management of this condition.
1 September 2017 in Journal of Pharmaceutical and Biomedical Analysis
Background: Extended criteria donors (ECD) are widely utilized due to organ shortage, but they may increase the risk of graft dysfunction and poorer outcomes. Hypothermic oxygenated perfusion (HOPE) is a recent organ preservation strategy for marginal kidney and liver grafts, allowing a redirect from anaerobic metabolism to aerobic metabolism under hypothermic conditions and protecting grafts from oxidative species–related damage. These mechanisms may improve graft function and survival. Objective: With this study, we will evaluate the benefit of end-ischemic HOPE on ECD grafts for livers and kidneys as compared to static cold storage (SCS). The aim of the study is to demonstrate the ability of HOPE to improve graft function and postoperative outcomes of ECD kidney and liver recipients. Methods: This is an open-label, single-center randomized clinical trial with the aim of comparing HOPE with SCS in ECD kidney and liver transplantation. In the study protocol, which has been approved by the ethics committee, 220 patients (110 liver recipients and 110 kidney recipients) will be enrolled. Livers and kidneys assigned to the HOPE group undergo machine perfusion with cold Belzer solution (4-10°C) and continuous oxygenation (partial pressure of oxygen of 500-600 mm Hg). In the control group, livers and kidneys undergoing SCS are steeped in Celsior solution and stored on ice. Using the same perfusion machine for both liver and kidney grafts, organs are perfused from the start of the back-table procedure until implantation, without increasing the cold ischemia time. For each group, we will evaluate clinical outcomes, graft function tests, histologic findings, perfusate, and the number of allocated organs. Publication of the results is expected to begin in 2021. Results: Dynamic preservation methods for organs from high-risk donors should improve graft dysfunction after transplantation. To date, we have recruited 108 participants. The study is ongoing, and recruitment of participants will continue until January 2020. Conclusions: The proposed preservation method should improve ECD graft function and consequently the postoperative patient outcomes. Trial Registration: ClinicalTrials.gov NCT03837197; https://clinicaltrials.gov/ct2/show/NCT03837197 ; Archived by WebCite® at http://www.webcitation.org/76fSutT3R International Registered Report Identifier (IRRID): DERR1-10.2196/13922
Background and Aims: The PREDICT study recently showed that acutely decompensated (AD) patients with cirrhosis can present three different clinical phenotypes in the 90 days after admission: (1) pre‐ACLF, developing acute‐on‐chronic liver failure (ACLF); (2) unstable decompensated cirrhosis (UDC), being re‐admitted for AD without ACLF and (3) stable decompensated cirrhosis (SDC), not presenting readmission or ACLF. This study aimed to externally validate the existence of these three distinct trajectories and to identify predictors for the occurrence of each trajectory.Methods: Baseline data, 3‐month ACLF and readmission incidence and 1‐year survival were analysed in a prospective cohort of patients admitted for AD. A multinomial multivariable model was used to evaluate the association between baseline features and clinical trajectories.Results: Of the 311 patients enrolled, 55% met the criteria for SDC, 18% for UDC and 27% for pre‐ACLF, presenting a significantly different 1‐year mortality: pre‐ACLF 65%, UDC 46%, SDC 21% (p < .001). The presence of hepatic encephalopathy (HE) was associated with UDC (p = .043), while the absence of ascites to SDC (p = .017). Among laboratory parameters, an increase in MELD‐Na (p = .001) and C‐reactive protein (p = .009) and a decrease in haemoglobin (p = .004) and albumin (p = .008) levels were associated with pre‐ACLF.Conclusion: The present study confirms that AD patients have three different clinical trajectories with different mortality rates. Besides the severity of cirrhosis, the association with C‐reactive protein supports the predominant role of systemic inflammation in ACLF pathophysiology. Finally, HE is associated with the UDC phenotype highlighting the need for better management of this complication after discharge.