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Balancing human communities’ and ecosystems’ need for freshwater is one of the major challenges of the 21st century as population growth and improved living conditions put increasing pressure on freshwater resources. While frameworks to assess the environmental impacts of freshwater consumption have been proposed at the regional scale, an operational method to evaluate the consequences of consumption on different compartments of the water system and account for their interdependence is missing at the global scale. Here, we develop depletion factors that simultaneously quantify the effects of water consumption on streamflow, groundwater storage, soil moisture, and evapotranspiration globally. We estimate freshwater availability and water consumption using the output of a global-scale surface water-groundwater model for the period 1960-2000. The resulting depletion factors are provided for 8,664 river basins, representing 93% of the landmass with significant water consumption, i.e., excluding Greenland, Antarctica, deserts, and permanently frozen areas. Our findings show that water consumption leads to the largest water loss in rivers, followed by aquifers and soil, while simultaneously increasing evapotranspiration. Depletion factors vary regionally with ranges of up to four orders of magnitude depending on the annual consumption level, the type of water used, aridity, and water transfers between compartments. Our depletion factors provide valuable insights into the intertwined effects of surface and groundwater consumption on several hydrological variables over a specified period. The developed depletion factors can be integrated into sustainability assessment tools to quantify the ecological impacts of water consumption and help guide sustainable water management strategies, while accounting for the performance limitations of the underlying model.

Summary Introduction Prehabilitation is defined as preoperative conditioning of patients in order to improve post-operative outcomes. Some studies showed an increase in functional recovery following colorectal surgery, but its effect in hepato-pancreato-biliary (HPB) surgery is unclear. The aim of this study was to realize a systematic literature review and meta-analysis on the current available evidence on prehabilitation in HPB surgery. Materials and methods A systematic review and a metanalysis were carried out on prehabilitation (physical, nutritional and psychological interventions) in HPB surgery (2009-2019). Assessed outcomes were postoperative complications, length of stay (LOS), 30-day readmission, and mortality. Main results Four studies among the 191 screened were included in this systematic review (3 randomized controlled trials, 1 case-control propensity score study), involving 419 patients (prehabilitation group, n = 139; control group, n = 280). After pooling, no difference was observed on LOS ((−4.37 days [95% CI: −8.86; 0.13]) or postoperative complications (RR 0.83 [95%CI: 0.62; 1.10]), reported by all the included studies. Two trials reported on readmission rate, but given the high heterogeneity, a meta-analysis was not realized. No deaths were reported among the included studies. Conclusion No effect of prehabilitation programs in HPB surgery was observed on LOS or postoperative complications rate. Future trials with standardized outcomes of measure, and adequately powered samples calculations are thus required. PROSPERO registration CRD42020165218.

Resume Introduction La prehabilitation peut etre definie comme un conditionnement preoperatoire des patients afin d’ameliorer les resultats fonctionnels apres chirurgie. Certaines etudes ont montre une meilleure recuperation fonctionnelle apres chirurgie colorectale, mais son impact en chirurgie hepato-bilio-pancreatique (HPB) n’est pas demontre. L’objectif de cette etude est de realiser une revue systematique de la litterature et une meta-analyse des donnees actuellement disponibles sur la prehabilitation en chirurgie HPB. Materiaux et methodes Une revue systematique et une meta-analyse ont ete realisees sur la prehabilitation (interventions physiques, nutritionnelles et psychologiques) en chirurgie HPB (2009–2019). Les criteres de jugement evalues etaient les complications postoperatoires, la duree du sejour, la readmission a 30 jours et la mortalite. Principaux resultats Quatre etudes parmi les 191 examinees ont ete incluses dans cette revue systematique (trois essais controles randomises, une etude cas-temoin sur score de propension) portant sur un total de 419 patients (groupe de prehabilitation, n = 139 ; groupe temoin, n = 280). Apres analyse, aucune difference entre les deux groupes n’a ete observee sur la duree d’hospitalisation (−3,1 jours [IC a 95 % : −6,3 ;0,1]) ni sur le taux de complications postoperatoires (RR 0,83 [IC a 95 % : 0,62 ;1,10]). Deux essais ont evalue le taux de readmission, mais compte tenu d’une heterogeneite elevee, aucune meta-analyse n’a ete realisee. Aucun deces n’a ete rapporte parmi les etudes incluses. Conclusion Sur la base des donnees disponibles il n’a pas ete observe d’impact des programmes de prehabilitation en chirurgie HPB sur la duree d’hospitalisation ou le taux de complications postoperatoires. Des futurs essais avec des criteres de jugement standardises, et avec un echantillon de patients adequat sont necessaires. Prospero Registration CRD42020165218.

Patients with hepatocellular carcinoma (HCC) displaying overexpression of immune gene signatures are likely to be more sensitive to immunotherapy, however, the use of such signatures in clinical settings remains challenging. We thus aimed, using artificial intelligence (AI) on whole-slide digital histological images, to develop models able to predict the activation of 6 immune gene signatures.AI models were trained and validated in 2 different series of patients with HCC treated by surgical resection. Gene expression was investigated using RNA sequencing or NanoString technology. Three deep learning approaches were investigated: patch-based, classic MIL and CLAM. Pathological reviewing of the most predictive tissue areas was performed for all gene signatures.The CLAM model showed the best overall performance in the discovery series. Its best-fold areas under the receiver operating characteristic curves (AUCs) for the prediction of tumors with upregulation of the immune gene signatures ranged from 0.78 to 0.91. The different models generalized well in the validation dataset with AUCs ranging from 0.81 to 0.92. Pathological analysis of highly predictive tissue areas showed enrichment in lymphocytes, plasma cells, and neutrophils.We have developed and validated AI-based pathology models able to predict the activation of several immune and inflammatory gene signatures. Our approach also provides insights into the morphological features that impact the model predictions. This proof-of-concept study shows that AI-based pathology could represent a novel type of biomarker that will ease the translation of our biological knowledge of HCC into clinical practice.Immune and inflammatory gene signatures may be associated with increased sensitivity to immunotherapy in patients with advanced hepatocellular carcinoma. In the present study, the use of artificial intelligence-based pathology enabled us to predict the activation of these signatures directly from histology.

To evaluate the accuracy of the usual MRI diagnostic patterns of primary liver lesions applied to the diagnosis of pathologically proven fat-containing liver lesions.This monocentric IRB approved retrospective study included all patients with pathologically proven focal liver lesions and documented intra-tumoral fat on pathology and who underwent preoperative liver MRI for characterization. Both liver morphology and usual lesion MRI features were analyzed and their distribution correlated to the final pathological result (Khi-2 or Fisher exact tests, Student t-test or Mann-Whitney U test, as appropriate). The Sensitivity (Se) and Specificity (Sp) of MRI patterns known to be associated to both Hepatocellular Carcinoma (HCC), Focal Nodular Hyperplasia (FNH), and Hepatocellular Adenoma (HCA) subtypes were evaluated.Between March 2014 and November 2021, 66 lesions were included, corresponding to: 26 HCC, 32 HCA, 6 FNH and 2 hepatic angiomyolipoma (HAML). All lesions developed on a dysmorphic liver were HCC. A non-rim arterial phase hyperenhancement with a washout and an enhancing capsule had a 98% specificity for HCC diagnosis; A homogeneous dropout of signal on the opposed phase had a sensitivity of 92% and a specificity of 89% for the diagnosis of HNF1alpha inactivated subtype of HCA (HHCA). The FNH pattern was specific at 100% for the diagnosis of FNH with a 40% Se. Finally, the accuracy of inflammatory hepatocellular adenoma (IHCA) pattern had a low 60% Se but a high 89% Sp for IHCA diagnosis.Known MRI patterns remain reliable for the accurate diagnosis of primary liver tumors on MRI even in fat-containing lesions.

Supplemental figures 1-10

Supplementary Table 5: Difference in gene expression between Immune High (IH) and Immune Low (IL) subgroups from the validation dataset (n=20, Coulouarn et al, Carcinogenesis, 2012) (33).

Supplementary Table 3: Difference in gene expression between IH1 and IH2 subtypes IH: Immune - High

Supplemental Data

Supplementary Table 1: Difference in gene expression between IL and IH subtypes

Supplementary Table 6: Difference in gene expression between Immune High 1 (IH1) and Immune High 2 (IH2) subgroups in the validation dataset (n=20, Coulouarn et al, Carcinogenesis, 2012) (33).

Supplementary Table 8: Molecular alterations identified in cHCC-CCA

Supplementary Table 7: Difference in gene expression between Immune Low 1 (IL1) and Immune Low 2 (IL2) subgroups in the validation dataset (n=20, Coulouarn et al. Carcinogenesis. 2012) (33).

Supplementary Table 4: Difference in gene expression between IL1 and IL2 subtypes IL: Immune - Low

Purpose:Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome.Experimental Design:We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing.Results:Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an “immune-high” (IH) subtype (57% of the cases) and an “immune-low” (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P < 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival.Conclusions:We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.

Purpose:Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a novel morphological subtype of HCC associated with early relapse after resection or percutaneous ablation, independently of classical clinical and radiological prognostic factors. The aim of the present study was to identify immunohistochemical markers of MTM-HCC, to ease its diagnosis and implementation into clinical practice.Experimental Design:To identify potential biomarkers of MTM-HCC, we first analyzed gene expression profiling data from The Cancer Genome Atlas study and further selected two candidate biomarkers. Performance of both biomarkers for diagnosis of MTM-HCC was further tested by immunohistochemistry in two independent series of 67 and 132 HCC biopsy samples.Results:Analysis of RNA sequencing data showed that MTM-HCC was characterized by a high expression of neoangiogenesis-related genes. Two candidate biomarkers, Endothelial-Specific Molecule 1 (ESM1) and Carbonic Anhydrase IX (CAIX), were selected. In the discovery series, sensitivity and specificity of ESM1 expression by stromal endothelial cells for the detection of MTM-HCC were 97% (28/29), and 92% (35/38), respectively. Sensitivity and specificity of CAIX were 48% (14/29) and 89% (34/38). In the validation set, sensitivity and specificity of ESM1 for the identification of MTM-HCC were 93% (14/15) and 91% (107/117), respectively. Interobserver agreement for ESM1 assessment was good in both series (Cohen Kappa 0.77 and 0.76).Conclusions:Using a molecular-driven selection of biomarkers, we identified ESM1 as a reliable microenvironment immunohistochemical marker of MTM-HCC. The results represent a step toward the implementation of HCC morpho-molecular subtyping into clinical practice.

Supplementary Figure 2 from Controlling Tumor Growth by Modulating Endogenous Production of Reactive Oxygen Species

Paradoxically, reactive oxygen species (ROS) can promote normal cellular proliferation and carcinogenesis, and can also induce apoptosis of tumor cells. In this report, we study the contribution of ROS to various cellular signals depending on the nature and the level of ROS produced. In nontransformed NIH 3T3 cells, ROS are at low levels and originate from NADPH oxidase. Hydrogen peroxide (H2O2), controlled by the glutathione system, is pivotal for the modulation of normal cell proliferation. In CT26 (colon) and Hepa 1-6 (liver) tumor cells, high levels of ROS, close to the threshold of cytotoxicity, are produced by mitochondria and H2O2 is controlled by catalase. N-acetylcysteine, which decreases H2O2 levels, inhibits mitogen-activated protein kinase and normal cell proliferation but increases tumor cell proliferation as H2O2 concentration drops from the toxicity threshold. In contrast, antioxidant molecules, such as mimics of superoxide dismutase (SOD), increase H2O2 levels through superoxide anion dismutation, as well as in vitro proliferation of normal cells, but kill tumor cells. CT26 tumors were implanted in mice and treated by oxaliplatin in association with one of the three SOD mimics manganese(III)tetrakis(4-benzoic acid) porphyrin, copper(II)(3,5-diisopropylsalicylate)2, or manganese dipyridoxyl diphosphate. After 1 month, the volumes of tumors were respectively 35%, 31%, and 63% smaller than with oxaliplatin alone (P < 0.001). Similar data were gained with Hepa 1-6 tumors. In conclusion, antioxidant molecules may have opposite effects on tumor growth. SOD mimics can act in synergy with cytotoxic drugs to treat colon and liver cancers.

Supplementary Figure 1 from Controlling Tumor Growth by Modulating Endogenous Production of Reactive Oxygen Species

Supplementary Figure 3 from Controlling Tumor Growth by Modulating Endogenous Production of Reactive Oxygen Species

Background: Assessment of hepatocellular carcinoma (HCC) treatment response after transarterial radioembolization (TARE) is challenging, as response by conventional imaging criteria may not become ...

The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated. BACKGROUND The impact of obesity on surgical outcomes in elderly patients candidate for liver surgery is still debated. AIM To evaluate the impact of high body mass index (BMI) on perioperative and oncological outcome in elderly patients (> 70 years old) treated with laparoscopic liver resection for hepatocellular carcinoma (HCC). METHODS Retrospective multicenter study including 224 elderly patients (> 70 years old) operated by laparoscopy for HCC (196 with a BMI < 30 and 28 with BMI ≥ 30), observed from January 2009 to January 2019. RESULTS After propensity score matching, patients in two groups presented comparable results, in terms of operative time (median range: 200 min vs 205 min, P = 0.7 respectively in non-obese and obese patients), complications rate (22% vs 26%, P = 1.0), length of hospital stay (median range: 4.5 d vs 6.0 d, P = 0.1). There are no significant differences in terms of short- and long-term postoperative results. CONCLUSION The present study showed that BMI did not impact perioperative and oncologic outcomes in elderly patients treated by laparoscopic resection for HCC. journal article 2023 Jan 27 imported

Introduction: Currently, the impact of body mass index (BMI) on the outcomes of laparoscopic liver resections (LLR) is poorly defined. This study attempts to evaluate the impact of BMI on the peri-operative outcomes following laparoscopic left lateral sectionectomy (L-LLS). Methods: A retrospective analysis of 2183 patients who underwent pure L-LLS at 59 international centers between 2004 and 2021 was performed. Associations between BMI and selected peri-operative outcomes were analyzed using restricted cubic splines. Results: A BMI of >27kg/m2 was associated with increased in blood loss (Mean difference (MD) 21 mls, 95% CI 5–36), open conversions (Relative risk (RR) 1.13, 95% CI 1.03–1.25), operative time (MD 11 min, 95% CI 6–16), use of Pringles maneuver (RR 1.15, 95% CI 1.06–1.26) and reductions in length of stay (MD -0.2 days, 95% CI -0.3 to −0.1). The magnitude of these differences increased with each unit increase in BMI. However, there was a “U” shaped association between BMI and morbidity with the highest complication rates observed in underweight and obese patients. Conclusion: Increasing BMI resulted in increasing difficulty of L-LLS. Consideration should be given to its incorporation in future difficulty scoring systems in laparoscopic liver resections.

Several water footprint indicators have been developed to curb freshwater stress. Volumetric footprints support water allocation decisions and strive to increase water productivity in all sectors. In contrast, impact-oriented footprints are used to minimize the impacts of water use on human health, ecosystems, and freshwater resources. Efforts to combine both perspectives in a harmonized framework have been undertaken, but common challenges remain, such as pollution and ecosystems impacts modelling. To address these knowledge gaps, we build upon a water footprint assessment framework proposed at conceptual level to expand and operationalize relevant features. We propose two regionalized indicators, namely the water biodiversity footprint and the water resource footprint, that aggregate all impacts from toxic chemicals, nutrients, and water scarcity. The first impact indicator represents the impacts on freshwater ecosystems. The second one models the competition for freshwater resources and its consequences on freshwater availability. As part of the framework, we complement the two indicators with a sustainability assessment representing the levels above which ecological and human freshwater needs are no longer sustained. We test our approach assessing the sustainability of water use in the European Union in 2010. Water stress hampers 15 % of domestic, agricultural and industrial water demand, mainly due to irrigation and pesticide emissions in southern Europe. Moreover, damages to the freshwater ecosystems are widespread and mostly resulting from chemical emissions from industry. Approximately 5 % of the area is exceeding the regional sustainability limits for ecosystems and human water requirements altogether. Concerted efforts from all sectors are needed to reduce the impacts of emissions and water consumption under the sustainability limits. These advances are considered an important step toward the harmonization of volumetric and impact-oriented approaches to achieve consistent and holistic water footprinting as well as contributing to strengthen the policy relevance of water footprint assessments.

The ABO blood group system may influence tumorigenesis, but its prognostic value in liver transplantation (LT) for hepatocellular carcinoma (HCC) has never been assessed.All consecutive patients who underwent LT for HCC between 2013 and 2017 at 9 centers were analyzed. Predictors of tumor recurrence were identified using multivariable analysis, while comparison between group A and non-A recipients was performed after propensity score matching.Among 925 LT recipients, 406 were blood group A, 94 group B, 380 group O, and 45 group AB. On multivariable analysis, group A was associated with tumor recurrence (hazard ratio [HR] = 1.574 [95% confidence interval; 95% CI = 1.034-2.394] P = 0.034). After propensity score matching, 1- and 5-y recurrence rates were 7.4% and 20.1% in group A recipients versus 3.3% and 13.2% in non-A recipients (HR = 1.66 [95% CI = 1.12-2.45], P = 0.011). One and 5-y recurrence-free survivals were 85.2% and 66.8% in group A recipients versus 88.5% and 71.3% in non-A recipients (HR = 1.38 [95% CI = 1.01-1.90], P = 0.045). Among recipients within Milan criteria (n = 604), 1- and 5-y recurrence rates were 5.8% and 12.7% in group A recipients versus 3.1% and 12.2% in non-A recipients (HR = 1.197 [95% CI = 0.721-1.987], P = 0.485). Among recipients outside Milan criteria (n = 182), 1- and 5-y recurrence rates were 12.1% and 43.8% in group A recipients versus 3.9% and 15.6% in non-A recipients (HR = 3.175 [95% CI = 1.526-6.608], P = 0.002).ABO blood system influences the oncological outcome of recipients undergoing LT for HCC. Its incorporation in the prognostication model of LT for HCC may allow improving the management of LT candidates.

Treatment of extensive chondral and osteochondral defects in the knee remains a challenge. The traditional bone marrow stimulation and osteochondral mosaicplasty are effective but this is indicated only for lesions smaller than 4 cmDans le traitement des défects chondraux et ostéochondraux du genou, les techniques classiques de réparation par stimulation de la moelle osseuse et de greffe ostéochondrale autologue (mosaicplastie) présentent d’importantes limites quant à la taille des lésions traitables (4 cm

Environmental dissipation is a novel approach to account for impacts from mineral resources. In contrast to all other resource-related life cycle impact assessment methods, which use data on extractions as input to calculation of indicator scores, environmental dissipation is characterized solely through emissions to the environment. Making environmental dissipation work as a viable resource use impact category in life cycle assessment requires, however, that truly dissipative emissions are differentiated from those anthropogenic releases which do not contribute to loss of accessibility of a given resource over the time frame considered. We present a new method that allows for this differentiation to be made for 65 metals and metalloids in a consistent way. It determines (1) whether an emission flow reported in a life cycle inventory actually contributes to loss of accessibility of a given element when environmental fate mechanisms are considered, and (2) whether the element comes from a source that would be considered as a mineral resource for any generation living between the present and the time frame of assessment. We apply the new method to four different emission inventories, and characterize the resulting list of truly dissipative emissions using recently proposed long-term environmental dissipation potentials (EDP). This highlights the need to differentiate dissipative emissions from other anthropogenic, potentially nondissipative emission flows of elements in metal resource impact assessment.

BACKGROUND Surgical resection and radiofrequency ablation (RFA) represent two possible strategy in treatment of hepatocellular carcinoma (HCC) in Milan criteria. AIM To evaluate short- A nd long-term outcome in elderly patients (70 years) with HCC in Milan criteria, which underwent liver resection (LR) or RFA. METHODS The study included 594 patients with HCC in Milan criteria (429 in LR group and 165 in RFA group) managed in 10 European centers. Statistical analysis was performed using the Kaplan-Meier method before and after propensity score matching (PSM) and Cox regression. RESULTS After PSM, we compared 136 patients in the LR group with 136 patients in the RFA group. Overall survival at 1, 3, and 5 years was 91%, 80%, and 76% in the LR group and 97%, 67%, and 41% in the RFA group respectively (P = 0.001). Diseasefree survival at 1, 3, and 5 years was 84%, 60% and 44% for the LR group, and 63%, 36%, and 25% for the RFA group (P = 0.001).Postoperative Clavien-Dindo IIIIV complications were lower in the RFA group (1% vs 11%, P = 0.001) in association with a shorter length of stay (2 d vs 7 d, P = 0.001).In multivariate analysis, Model for End-stage Liver Disease (MELD) score (10) [odds ratio (OR) = 1.89], increased value of international normalized ratio (1.3) (OR = 1.60), treatment with radiofrequency (OR = 1.46) ,and multiple nodules (OR = 1.19) were independent predictors of a poor overall survival while a high MELD score (10) (OR = 1.51) and radiofrequency (OR = 1.37) were independent factors associated with a higher recurrence rate. CONCLUSION Despite a longer length of stay and a higher rate of severe postoperative complications, surgery provided better results in long-term oncological outcomes as compared to ablation in elderly patients (70 years) with HCC in Milan criteria. © 2021 The Author(s). Published by Baishideng Publishing Group Inc. All rights reserved.

The planetary boundaries define a safe operating space for humanity to act within without potentially destabilizing the planet. The safe operating space is often used a sustainability reference in Absolute Environmental Sustainability Assessments (AESAs) where a share of the safe operating space (SoSOS) is assigned to the assessed activity. An identified challenge, is that current methods are suited for business-to-consumer (B2C) industries and companies, but ill-suited for assessments of business-to-business (B2B) as the sharing is often based on the direct value to humans. Thus, this study presents a systematic framework for assigning a SoSOS to both B2C and B2B industries and companies. The framework uses multi-region input-output models to link industries and estimate the direct and indirect value to humans for both B2B and B2C industries. The framework was tested in a case study for a B2B company to show its application and to evaluate the sensitivity of the framework towards different modelling choices. The results of the case study and sensitivity analysis was used to provide recommendations for further improvement of the framework. While there is still need for improvement and refinement, the framework shows large potential. Mainly because it directly facilitate AESA of B2B industries and companies to help gauging their environmental performance relative to absolute boundaries and, thus, provide better basis supporting strategic sustainability related activities.

Several gaps and limitations characterise present indicators for United Nations’ Sustainable Development Goal 7 (SDG-7), thus impeding effective policy-making. Here, we propose a holistic framework which enables the assessment of national SDG-7 performances through 29 indicators capturing environmental as well as socio- and techno-economic aspects specifically relevant to the sustainability of the energy sector. The framework is applied to 176 countries, benchmarking indicator scores against absolute sustainability thresholds and targets to gauge how far current energy systems are from reaching truly sustainable levels. Our results reveal different performance patterns across countries as well as trade-offs between social and environmental indicators. All countries are found to exert unsustainable performances for several indicators, albeit with large variability, where some environmental scores lie just above the threshold and others exceed by more than a factor of 1000. Climate change impact scores are examples of the latter, where only 52 countries located in Africa and Asia are found to possibly show performances below their thresholds. With this quantitative and holistic support at the country level, it becomes possible for policy-makers to identify, prioritise and target specific sustainability aspects to achieve SDG-7, and not just move towards it. Therefore, we recommend a broad uptake of our framework while continuing its development, including for other SDGs.

Liver resection (LR) and radiofrequency ablation (RFA) are considered curative options for hepatocellular carcinoma (HCC). The aim of this study was to compare outcomes after LR and RFA in octogenarian patients with HCC.This multicenter retrospective study included 102 elderly patients ( 80 years old) treated between January 2009 and January 2019, who underwent LR or RFA for HCC (65 and 37 with, respectively).After Propensity Score Matching, the postoperative course of LR was burdened by a higher rate of complications than RFA group (64% vs 14%, respectively, p: 0.001). The LR group had also significantly longer operative time (207 ± 85 min vs 33 ± 49 min, p 0.001) and postoperative hospital stays than the RFA group (7 d vs 2 d, p = 0.019). Overall survival at 1-, 2-, and 3-year were 86%, 86%, and 70% for the LR group and 82%, 64%, and 52% for the RFA group (p = 0.380). Disease-free survival at 1-, 2-, and 3-year were 89%, 74%, and 56% for the LR group, and 51%, 40%, and 40% for the RFA group (p = 0.037).Despite a higher rate of Dindo-Clavien I-II post-operative complications, a longer operative time and length of hospital stay, LR in octogenarian patients can provide comparable 90d mortality than RFA and better long-term outcomes.

Background: To evaluate the cost-effectiveness of the extended use of ablation for the treatment of hepatocellular carcinoma (HCC) with cirrhosis in an expert ablation center when compared to the non-extended use of ablation in equivalent tertiary care centers. Methods: Consecutive cirrhotic patients with non-metastatic HCC, no prior treatment, and referred to three tertiary care centers between 2012 and 2016 were retrospectively identified. The Bondy group, including all of the patients treated at Jean Verdier Hospital, where the extended use of ablation is routinely performed, was compared to the standard of care (SOC) group, including all of the patients treated at the Beaujon and Mondor Hospitals, using propensity score matching. A cost-effectiveness analysis was carried out from the perspective of French health insurance using a Markov model on a lifetime horizon. Results: 532 patients were matched. The Bondy group led to incremental discounted lifetime effects of 0.8 life-years gained (LYG) (95% confidence interval: 0.4, 1.3) and a decrease in lifetime costs of EUR 7288 (USD 8016) (95% confidence interval: EUR 5730 [USD 6303], EUR 10,620 [USD 11,682]) per patient, compared with the SOC group, resulting in a dominant mean incremental cost-effectiveness ratio (ICER). A compliance with the Barcelona Clinic Liver Classification (BCLC) guidelines for earlier stage contributed to the greater part of the ICER. Conclusion: The extended use of ablation in cirrhotic patients with HCC was more effective and less expensive than the non-extended use of the ablation strategy.

Background: Systemic fungal infections are an important mortality factor when considering severely burned patients. Preventive topical pharmacotherapeutic management of deep fungal infections remains of secondary concern when initially treating a burn victim, despite high inherent lethal risks. Indeed, the possible subsequent invasions of newly accessible deep tissues and bone by opportunistic fungi often prove fatal. Amphotericin B is a broad-spectrum antifungal agent of choice for infections in burn victims. Intravenous administration is limited by drug-related nephrotoxicity. Novel topical Amphotericin B preparations to be applied in burn centers would therefore limit the systemic adverse effects of the active principle while preventing dissemination of sensitive pathogens and thus help reducing infectious and drug-related mortality. Objective: To establish the need for new topical pharmacotherapeutic management options to treat burn wound fungal infections and conceptually determine the applicability of liposomal Amphotericin B for such cases. Methods: Experimental liposomal Amphotericin B was prepared with commercial components and tested in vitro in our mycology laboratory to determine efficacy, stability and potential for topical application on our burn patients. Results: Data showed equivalent or superior in vitro activity of liposomal Amphotericin B versus unbound drug against Aspergillus fumigatus and superior physical and pharmacologic effect stability over time. Conclusion: Topical and relatively inexpensive liposomal Amphotericin B as described in this work is an interesting, potentially mortality-reducing candidate regarding fungal infections in early and severe burn wound management.

Life cycle impact assessment (LCIA) is a lively field of research, and data and models are continuously improved in terms of impact pathways covered, reliability, and spatial detail. However, many of these advancements are scattered throughout the scientific literature, making it difficult for practitioners to apply the new models. Here, we present the LC‐IMPACT method that provides characterization factors at the damage level for 11 impact categories related to three areas of protection (human health, ecosystem quality, natural resources). Human health damage is quantified as disability adjusted life years, damage to ecosystem quality as global species extinction equivalents (based on potentially disappeared fraction of species), and damage to mineral resources as kilogram of extra ore extracted. Seven of the impact categories include spatial differentiation at various levels of spatial scale. The influence of value choices related to the time horizon and the level of scientific evidence of the impacts considered is quantified with four distinct sets of characterization factors. We demonstrate the applicability of the proposed method with an illustrative life cycle assessment example of different fuel options in Europe (petrol or biofuel). Differences between generic and regionalized impacts vary up to two orders of magnitude for some of the selected impact categories, highlighting the importance of spatial detail in LCIA. This article met the requirements for a gold – gold JIE data openness badge described at http://jie.click/badges., Journal of Industrial Ecology, 24 (6), ISSN:1088-1980, ISSN:1530-9290