The Model for End‐Stage Liver Disease (MELD) score has reduced accuracy for liver transplantation (LT) wait‐list mortality when MELD ≤ 20. Neutrophil‐to‐lymphocyte ratio (NLR) is a biomarker ...associated with systemic inflammation and may predict cirrhotic decompensation and death. We aimed to evaluate the prognostic utility of high NLR (≥4) for liver‐related death among low MELD patients listed for LT, controlling for stage of cirrhosis. In a nested case‐control study of cirrhotic adults awaiting LT (February 2002 to May 2011), cases were LT candidates with a liver‐related death and MELD ≤ 20 within 90 days of death. Controls were similar LT candidates who were alive for ≥90 days after LT listing. NLR and other covariates were assessed at the date of lowest MELD, within 90 days of death for cases and within 90 days after listing for controls. There were 41 cases and 66 controls; MELD scores were similar. NLR 25th, 50th, 75th percentile cutoffs were 1.9, 3.1, and 6.8. NLR was ≥ 4 in 25/41 (61%) cases and in 17/66 (26%) controls. In univariate analysis, NLR (continuous ≥ 1.9, ≥ 4, ≥ 6.8), increasing cirrhosis stage, jaundice, encephalopathy, serum sodium, and albumin and nonselective beta‐blocker use were significantly (P < 0.01) associated with liver‐related death. In multivariate analysis, NLR of ≥1.9, ≥ 4, ≥ 6.8 were each associated with liver‐related death. Furthermore, we found that NLR correlated with the frequency of circulating low‐density granulocytes, previously identified as displaying proinflammatory properties, as well as monocytes. In conclusion, elevated NLR is associated with liver‐related death, independent of MELD and cirrhosis stage. High NLR may aid in determining risk for cirrhotic decompensation, need for increased monitoring, and urgency for expedited LT in candidates with low MELD. Liver Transplantation 23 155–165 2017 AASLD
The diet polyphenols are a secondary metabolites of plants able to act on inflammation process. Their anti-inflammatory activity is articulated through several mechanisms that are related to their ...antioxidative and radical scavengers properties. Our work is focused on a novel approach to inflammatory disease management, based on anti-glycative and matrix metalloproteinases (MMPs) inhibition effects, as a connected phenomena. To better understand these correlation, polyphenols Structure-Activity Relationship (SAR) studies were also reported. The antioxidant polyphenols inhibit the AGEs at different levels of the glycation process in the following ways: (1) prevention of Amadori adduct oxidation; (2) trapping reactive dycarbonyl compounds; (3) attenuation of receptor for AGEs (RAGE) expression. Moreover, several flavonoids with radical scavenging property showed also MMPs inhibition interact directly with MMPs or indirectly via radical scavengers and AGEs reduction. The essential polyphenols features involved in these mechanisms are C2-C3 double bond and number and position of hydroxyl, glycosyl and O-methyl groups. These factors induce a change in molecular planarity interfering with the hydrogen bond formation, electron delocalization and metal ion chelation. In particular, C2-C3 double bond improve the antioxidant and MMPs inhibition, while the hydroxylation, glycosylation and methylation induce a positive and negative correlation, respectively.
Background
Patient and public involvement (PPI) is a critical priority in research, policy, academia and advocacy organizations. PPI in dementia research is gaining momentum. However, these efforts ...are missing in international projects aimed at those living with advanced dementia in long‐term care (LTC) homes. Additional complexities can arise in enacting PPI within the context of integration of a palliative approach to care and experiences around end‐of‐life in (EOL) dementia. The mySupport study involved implementing the Family Carer Decision Support (FCDS) intervention for care partners of those living with advanced dementia in LTC in six countries.
Research Design and Objective
An interpretive description study was conducted to explore the perspectives of international researchers from six countries on engaging people with lived experiences of dementia and EOL care in research processes. The findings from this study informed the development of a PPI strategy and a subsequent toolkit for the FCDS intervention.
Findings
Thirty‐eight interviews were completed with project researchers: 12 from the United Kingdom, 8 from Canada, 7 from Ireland, 4 each from Italy and The Netherlands and 3 from the Czech Republic. Four broad themes describe international researchers' perspectives on advancing methods of engagement for people with lived experiences of dementia and EOL in international PPI activities: (1) Groundwork to engage in research; (2) planning for research activities is key; (3) focus on meaningful engagement and (4) having foresight for practical issues shaping PPI.
Discussion and Implications
International projects that involve PPI can present many sources of challenges. The findings in this study highlight important considerations for foundational work for incorporating PPI in international projects. Learning from world leaders and those with lived experiences in various regions can be insightful and help share tools and resources.
Patient or Public Contribution
PPI was envisioned as a critical part of conducting the mySupport study. The findings from this study informed the development of a PPI strategy and an international Strategic Guiding Council that included family carers of those living with advanced dementia in LTC homes in six countries. This manuscript focused on the perspectives of researchers on their engagement with people with lived experiences of dementia and EOL. The perspectives of persons with lived experiences on engaging in the mySupport research study will be reported in a forthcoming manuscript.
Purpose
To investigate the effects of CT protocol and in‐room x‐ray technique on CyberKnife® (Accuray Inc.) tracking accuracy by evaluating end‐to‐end tests.
Methods
End‐to‐end (E2E) tests were ...performed for the different tracking methods (6D skull, fiducial, spine, and lung) using an anthropomorphic head phantom (Accuray Inc.) and thorax phantom (CIRS Inc.). Bolus was added to the thorax phantom to simulate a large patient and to evaluate the performance of lung tracking in a more realistic condition. The phantoms were scanned with a Siemens Sensation Open 24 slice CT at low dose (120 kV, 70 mAs, 1.5 mm slice thickness) and high dose (120 kV, 700 mAs, 1.5 mm slice thickness) to generate low‐dose and high‐dose digitally reconstructed radiographs (DRRs). The difference in initial phantom alignment, Δ(Align), and in total targeting accuracy, E2E, were obtained for all tracking methods with low‐ and high‐dose DRRs. Additionally, Δ(Align) was determined for different in‐room x‐ray imaging techniques (0.5 to 50 mAs and 100 to 140 kV) using a low‐dose lung tracking plan.
Results
Low‐dose CT scans produced images with high noise; however, for these phantoms the targets could be easily delineated on all scans. End‐to‐end results were less than 0.95 mm for all tracking methods and all plans. The greatest difference in initial alignment Δ(Align) and E2E results between low‐ and high‐dose CT protocols was 0.32 and 0.24 mm, respectively. Similar results were observed with a large thorax phantom. Tracking using different in‐room x‐ray imaging techniques (mAs) corresponding to low exposures (resulting in high image noise) or high exposure (resulting in image saturation) had alignment accuracy Δ(Align) greater than 1 mm.
Conclusions
End‐to‐end targeting accuracy within tolerance (<0.95 mm) was obtained for all tracking methods using low‐dose CT protocols, suggesting that CT protocol should be set by target contouring needs. Additionally, high tracking accuracy was achieved for in‐room x‐ray imaging techniques that produce high‐quality images.
Scope
Well‐controlled glycation (generally limited to the early stages) has been proposed as a strategy to improve the physiochemical properties of dietary proteins, but the functional studies of ...glycation products are mostly on advanced glycation end‐products (AGEs) rather than early glycation products (EGPs). Since cytokines are important modulators of various biological processes, this study aims to determine whether EGPs and AGEs affected immune homeostasis differentially and do so through modulating macrophage‐derived factors.
Methods and results
Two systems (glycine‐glucose and whey protein isolate (WPI)‐glucose) are established to generate glycation products. They are applied to human macrophages (PMA‐differentiated U937 cells), and cell viability and cytokine production are measured. Furthermore, EGPs, AGEs, and their conditioned medium (CM) from macrophages are applied to human prostate cancer (PCa) cells with different etiology (LNCaP and PC‐3) and murine PCa cells (TRAMP‐C2) to determine their direct and indirect effects on PCa cell proliferation. EGPs enhance the production of immunosuppressive cytokines, and this enhancement is associated with increased PCa cell proliferation. In contrast, AGEs inhibit macrophages to secret cytokines, but increase PCa cell proliferation directly.
Conclusions
Our data suggest that EGPs promote the prostate tumor proliferation indirectly through modulating macrophages, while AGEs have a direct effect.
Early glycation products (EGPs) activate macrophages to produce cytokines/chemokines, which promote prostate cancer (PCa) cell proliferation. Advanced glycation end‐products (AGEs) decrease macrophage survival, and directly increase PCa cell proliferation.
Objectives/Hypothesis
The literature on outcomes of end‐to‐side (ETS) anastomoses for microvascular reconstruction of the head and neck is limited. This series reviews ETS in free tissue transfer ...(FTT) across multiple institutions to better understand their usage and associated outcomes.
Study Design
Retrospective review of 2482 consecutive patients across three tertiary institutions.
Methods
Adult patients (> 18) who received a FTT from 2006 to 2019 were included.
Results
Two hundred and twenty‐one FTT were identified as requiring at least one ETS anastomosis. These ETS cases had a failure rate of 11.2% in comparison to 3.8% in a cohort of end‐to‐end (ETE) cases (P < .001). ETS cases were significantly more likely to have a prior neck dissection (P < .001), suggesting the ETS method was utilized in select circumstances. A second ETS anastomosis improved survival of the FTT (P = .006), as did utilization of a coupler over suture (P = .002). Failure due to venous thrombosis was significantly more common with one ETS anastomosis instead of two ETS anastomoses (P = .042).
Conclusions
ETS is effective but is often used as a secondary technique when ETE is not feasible; as such, in this series, ETS was associated with higher failure. A second anastomosis and the use of the coupler for completing the anastomoses were associated with lower rates of failure.
Level of Evidence
3 Laryngoscope, 131:1286–1290, 2021
The soluble receptor for advanced glycation end-products (sRAGE) has been suggested that it acts as a decoy for capturing advanced glycation end-products (AGEs) and inhibits the activation of the ...oxidative stress and apoptotic pathways. Lung AGEs/sRAGE is increased in idiopathic pulmonary fibrosis (IPF). The objective of the study was to evaluate the AGEs and sRAGE levels in serum as a potential biomarker in IPF.
Serum samples were collected from adult patients: 62 IPF, 22 chronic hypersensitivity pneumonitis (cHP), 20 fibrotic non-specific interstitial pneumonia (fNSIP); and 12 healthy controls. In addition, 23 IPF patients were re-evaluated after 3-year follow-up period. Epidemiological and clinical features were recorded: age, sex, smoking habits, and lung function. AGEs and sRAGE were evaluated by ELISA, and the results were correlated with pulmonary functional test values.
IPF and cHP groups presented a significant increase of AGE/sRAGE serum concentration compared with fNSIP patients. Moreover, an inverse correlation between AGEs and sRAGE levels were found in IPF, and serum sRAGE at diagnosis correlated with FVC and DLCO values. Additionally, changes in serum AGEs and sRAGE correlated with % change of FVC, DLCO and TLC during the follow-up. sRAGE levels below 428.25 pg/ml evolved poor survival rates.
These findings demonstrate that the increase of AGE/sRAGE ratio is higher in IPF, although the levels were close to cHP. AGE/sRAGE increase correlates with respiratory functional progression. Furthermore, the concentration of sRAGE in blood stream at diagnosis and follow-up could be considered as a potential prognostic biomarker.
Adult Liver Allocation in Eurotransplant Jochmans, Ina; van Rosmalen, Marieke; Pirenne, Jacques ...
Transplantation,
07/2017, Volume:
101, Issue:
7
Journal Article
Peer reviewed
Open access
Liver allocation in Eurotransplant is complex because allocation rules need to follow not only the guidelines of the European Commission but also the specific regulations of each of the 7 ...Eurotransplant countries with active liver transplant programs. Thirty-eight liver transplant centers served a population of about 135 million in 2015. Around 1600 deceased donor livers are transplanted annually. The number of deceased organ donors remains stable but donor age is increasing. Nevertheless, liver utilization rates are unchanged at around 80%. Donation after circulatory determination of death (DCD) increased fourfold in the past decade. In Belgium and the Netherlands, DCDs were responsible for 30% of deceased donor liver transplant activity in 2015; Austria only occasionally transplants a DCD liver; other Eurotransplant countries do not have active DCD programs. The most frequent indications for liver transplantation are alcoholic liver disease, hepatocellular carcinoma, and viral hepatitis. Livers are allocated first internationally to high urgency status patients or those with an approved combined organ status (for a liver in combination with heart, lung, intestine, or pancreas) and then on a national basis where allocation is recipient-driven or center-driven, depending on country-specific rules. Median waiting time for an elective liver transplant was 4,4 months in 2015; high urgency status patients waited a median of 2 days for a suitable liver. Mortality on the waiting list was 18% in 2015, 4% of patients were delisted because they became unfit for transplantation. One-year and 5-year risk unadjusted adult patient survival after transplantation is 80% and 65%, respectively.
Background and Objective
The accumulation of advanced glycation end‐products (AGEs) seems to play an important role in the development of diabetes mellitus (DM)‐associated periodontitis; however, ...some aspects of this issue are still scarcely known, such as the expression of AGEs in type 1 DM‐associated periodontitis and the clinical factors able to affect their accumulation. This study aimed to clarify these points by evaluating the expression of AGEs in DM‐associated periodontitis.
Material and Methods
Sixteen systemically and periodontally healthy subjects and 48 subjects suffering from generalized, severe, chronic periodontitis (16 with type 1 DM, 16 with type 2 DM and 16 systemically healthy subjects) were studied clinically, periodontally and metabolically. The immunohistochemical expression of AGEs in gingival tissues was also evaluated.
Results
Subjects affected with type 1 DM presented a significantly higher percentage of AGE‐positive cells than did subjects affected with type 2 DM, not only in the epithelium, but also in vessels and fibroblasts. A positive and significant correlation was found between gingival expression of AGEs and length of time affected with DM both in type 1 and type 2 DM; glycated hemoglobin, lipid profile, body mass index and age did not correlate significantly with gingival AGEs in any of the classes of subjects studied.
Conclusions
Gingival AGEs are increased in both type 1 and type 2 DM‐associated periodontitis; however, the clinical parameter that determines their accumulation, and therefore their degree of influence on the development of DM‐associated periodontitis, may be the duration of DM.
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