Subnormothermic and Normothermic Ex Vivo Liver Perfusion as a Novel Preservation Technique

Due to the worldwide organ shortage, interest in the use of marginal liver allografts has increased. More widespread use of marginal grafts is limited by graft injury from cold storage and the risk of poor outcomes after transplantation. Warm (subnormothermic and normothermic) ex vivo liver perfusion has emerged as a novel preservation strategy to recover marginal organs and potentially increase the organ pool. Over the last decade, advances in the field have taken warm ex vivo liver perfusion from the laboratory to clinical trials. While most investigation thus far has focused on the rescue of marginal grafts for expansion of the donor pool, warm perfusion (WP) preservation also has great potential to facilitate novel graft interventions prior to transplantation

Woman as Peacemaker or the Ambivalent Politics of Myth

Certains arguments féministes en faveur d’une participation accrue des femmes à la sphère politique ont mobilisé le thème de la capacité supposément supérieure des femmes à prendre en compte la dimension relationnelle des rapports humains, acquise dans le cadre privé de la vie familiale et parfois considérée comme une disposition innée. Dans ce cadre, le mythe de la femme pacificatrice a gagné une certaine visibilité et a pu fonctionner comme un contre-mythe dans le contexte des luttes féministes des deux derniers siècles. Cette contribution examine les traductions et les usages politiques de ce mythe depuis Aristophane jusqu’aux débats autour de la parité et de l’éthique de la sollicitude, en passant par le mouvement suffragiste du début du siècle dernier, ainsi que les critiques qui lui ont été adressées.Feminist arguments in favor of an increased participation of women in the public and the political spheres have sometimes resorted to the thesis of an alleged superior ability of women to take into account the relational dimension of human life, whether acquired in the private experience of family life or considered to be an innate feminine disposition. In this context, the myth of woman as a peacemaker has gained visibility and indeed has sometimes functioned as a countermyth in feminist politics. This paper examines the occurrences and uses of this myth from Aristophanes to the debates surrounding the ethics of care, through the suffragist movement, as well as the critiques that have been addressed to it

Masking-efficacy and caries arrestment after resin infiltration or fluoridation of initial caries lesions in adolescents during orthodontic treatment - a randomised controlled trial.

OBJECTIVES The aim of this randomised, controlled, split-mouth trial was to assess the masking results in initial caries lesions (ICL) that were either resin infiltrated or fluoridated during treatment with fixed orthodontic appliances. METHODS Adolescent patients (age range:12-18years) with fixed orthodontic appliances who had developed ICL [ICDAS 1 or 2 (International Caries Detection and Assessment System)] during orthodontic treatment were consecutively recruited and randomly assigned to either resin infiltration with up to 3 etching procedures (Group:Inf) or to 3-monthly application of a fluoride varnish (Group:FV). Both interventions were performed according to the manufacturer's recommendations. Primary and secondary outcomes (ΔE, ICDAS, DIAGNOdent) included the evaluation of the appearance of the ICL before (T0), 1 week after (T1) treatment and at the last appointment before debonding (T2). RESULTS Fifteen patients (8females, 7males) with 57ICL were included. Mean (SD) observation time at the last appointment before debonding was 0.5 (0.3) years. At T0 FV and Inf did not differ significantly in ΔE (median ΔE0,FV(25th/75th percentiles):11.6 (8.7/20.3): ΔE0,Inf:15.1 (11.4/19.5); pT0=0.135), ICDAS (pT0=0.920) and DD (pT0=0.367). At T1 and T2 ΔE values (pT1<0.001,pT2<0.001), ICDAS scores (pT1<0.001,pT2<0.001) and DIAGNOdent values (pT1=<0.001,pT2=<0.001) for Inf were significantly reduced whereas ΔE values (pT1=0.382,pT2=0.072) and ICDAS scores (pT1=0.268,pT2<0.001) for FV remained unchanged. CONCLUSIONS Resin infiltration effectively masked ICL during treatment with fixed orthodontic appliances both immediately after application and at the last appointment before debonding. Furthermore, the visual appearance of fluoridated lesions was not as satisfactory as that of the infiltrated ones at both T1 and T2. CLINICAL SIGNIFICANCE Resin infiltration effectively masked ICL during treatment with fixed orthodontic appliances both immediately after application and at the last appointment before debonding. Furthermore, the visual appearance of fluoridated lesions was not as satisfactory as that of the infiltrated ones immediately after first application as well as half a year after application. TRIAL REGISTRATION German Clinical Trials Register (DRKS-ID: DRKS00011797)

Development, management, and resolution of biliary complications after living and deceased donor liver transplantation: A report from the adult‐to‐adult living donor liver transplantation cohort study consortium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97202/1/lt23595.pd

The impact of preexisting and post-transplant diabetes mellitus on outcomes following liver transplantation

Background: Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and post-transplant DM on liver transplant (LT) recipients.Method: A single centre retrospective analysis of prospectively collected data of LT recipients (1990–2015) was undertaken.Results: Of the 2,209 patients, 13% (n=298) had Pre-DM, 16% (n=362) developed PTDM, 5% (n=118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n=1,431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM was similar to that of patients with pre-DM. Incidence of PTDM peaked during first-year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), non-alcoholic fatty liver disease and the use of Tacrolimus and Sirolimus use were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycaemic control throughout the follow-up period. Those who developed t-HG seems to have a unique characteristic compared to others. Overall, 9%, 5%, and 8% developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, re-LT, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM.Conclusions: In this largest non-registry study, patients with pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up

Cytotoxicities and Quantitative Structure Activity Relationships of B13 Sulfonamides in HT-29 and A549 Cells

B13 analogues are being considered as therapeutic agents for cancer cells, since B13 is a ceramide analogue and inhibits ceramidase to promote apoptosis in cancer cells. B13 sulfonamides are assumed to have biological activity similar to B13, since they are made by bioisosterically substituting the carboxyl moiety of B13 with sulfone group. Twenty B13 sulfonamides were evaluated for their in vitro cytotoxicities against human colon cancer HT-29 and lung cancer A549 cell lines using MTT assays. Replacement of the amide group with a sulfonamide group increased cytotoxicity in both cancer cell lines. The sulfonamides with long alkyl chains exhibited activities two to three times more potent than that of B13 and compound (15) had the most potent activity with IC50 values of 27 and 28.7µM for HT-29 and A549, respectively. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were used to carry out QSAR molecular modeling of these compounds. The predictive CoMSIA models for HT-29 and A549 gave cross-validated q2 values of 0.703 and 0.830, respectively. From graphical analysis of these models, we suppose that the stereochemistry of 1,3-propandiol is not important for activity and that introduction of a sulfonamide group and long alkyl chains into B13 can increase cytotoxicity

Feasibility of Virtual Assessment of Physical Frailty in Solid Organ Transplant Recipients – A Single Centre, Observational Study

Objectives: To describe the feasibility of virtual assessments of physical frailty in solid organ transplant (SOT) recipients using a modified Fried Frailty Index (mFFI) and Short Physical Performance Battery (SPPB), and to describe the prevalence of frailty 12-months post-transplant using virtual assessment. Methods: Virtual assessments were performed using an e-questionnaire and a video-call for functional tests. Feasibility variables included: internet quality, video-call duration, presence of a companion, and adverse events. Results: 34 SOT recipients, median age 62 (46-67), 76% lung recipients, 47% female, were included. The video-call had a median duration of 12 minutes (10-15 min), without adverse events. A companion was present in 23 (68%) video-call assessments. Fifteen SOT recipients (44%) were classified as pre-frail by the mFFI, and none were frail. Three participants (8.8%) were classified as frail using the SPPB. Conclusion: Virtual frailty assessments can be used as an alternative to in-person assessments in SOT recipients

Ex vivo machine perfusion: current applications and future directions in liver transplantation

Background: Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose: To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods: A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results: Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion: Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs

Outcomes of Radiofrequency Ablation as First-Line Therapy for Hepatocellular Carcinoma less than 3 cm in Potentially Transplantable Patients

© 2019 European Association for the Study of the Liver Background & Aims: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy. Methods: We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged 2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria. Results: We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95% CI 1.25–3.02) and alpha-fetoprotein levels at the time of ablation (100–1,000 ng/ml: hazard ratio 2.05; 95% CI 1.10–3.83) were found to be predictors of post-RFA recurrence outside Milan criteria. Conclusion: RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA. Lay summary: Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients

Gender and Racial Disparity Among Liver Transplantation Professionals: Report of a Global Survey.

Equality, diversity, and inclusion (EDI) are fundamental principles. Little is known about the pattern of practice and perceptions of EDI among liver transplant (LT) providers. International Liver Transplant Society (ILTS) EDI Committee survey around topics related to discrimination, mentorship, and gender. Answers were collected and analyzed anonymously. Worldwide female leadership was also queried via publicly available data. The survey was e-mailed to 1312 ILTS members, 199 responses (40.7% female) were collected from 38 countries (15.2% response rate). Almost half were surgeons (45.7%), 27.6% hepatologists and 26.6% anesthetists. Among 856 LT programs worldwide, 8.2% of leadership positions were held by females, and 22% of division chiefs were female across all specialties. Sixty-eight of respondents (34.7%) reported some form of discrimination during training or at their current position, presumably related to gender/sexual orientation (20.6%), race/country of origin (25.2%) and others (7.1%). Less than half (43.7%) received mentorship when discrimination occurred. An association between female responses and discrimination, differences in compensation, and job promotion was observed. This survey reveals alarmingly high rate of experience with racial and gender disparity, lack of mentorship, and very low rates of female leadership in the LT field and calls to action to equity and inclusion