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Objective: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. Background: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. Methods: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. Results: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. Conclusions: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is increasingly recognized as a major risk factor for developing neurocognitive disorders, though this association remains controversial. Determination of risk factors for post-traumatic neurodegeneration in patients with TBI is critical given the high incidence of TBI. We hypothesized that cardiovascular and metabolic comorbidities, in addition to TBI severity, are associated with the risk of post-traumatic development of Alzheimer disease dementia (ADD). A case-controlled retrospective study was conducted using medical records and medical insurance data of 5642 patients with TBI admitted to a tertiary trauma center over a 12-year period, to assess risk factors of developing ADD after TBI. Logistic regression shows that presence of post-traumatic amnesia ( P= 0.03) and chronic vascular lesions ( P= 0.04) are significantly associated with development of ADD after TBI. This innovative preliminary study is the first to explore risk factors for post-traumatic ADD. Further association studies are essential to optimize care following TBI. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To assess the risk factors associated with R1 resection in patients undergoing OLS and LLS for CRLMs. Background: The clinical impact of R1 resection in liver surgery for CRLMs has been continuously appraised, but R1 risk factors have not been clearly defined yet. Methods: A cohort study of patients who underwent OLS and LLS for CRLMs in 9 European high-volume referral centers was performed. A multivariate analysis and the receiver operating characteristic curves were used to investigate the risk factors for R1 resection. A model predicting the likelihood of R1 resection was developed. Results: Overall, 3387 consecutive liver resections for CRLMs were included. OLS was performed in 1792 cases whereas LLS in 1595; the R1 resection rate was 14% and 14.2%, respectively. The risk factors for R1 resection were: the type of resection (nonanatomic and anatomic/nonanatomic), the number of nodules and the size of tumor. In the LLS group only, blood loss was a risk factor, whereas the Pringle maneuver had a protective effect. The predictive size of tumor for R1 resection was >45 mm in OLS and >30 mm in LLS, > 2 lesions was significative in both groups and blood loss >350 cc in LLS. The model was able to predict R1 resection in OLS (area under curve 0.712; 95% confidence interval 0.665–0.739) and in LLS (area under curve 0.724; 95% confidence interval 0.671–0.745). Conclusions: The study describes the risk factors for R1 resection after liver surgery for CRLMs, which may be used to plan better the perioperative strategies to reduce the incidence of R1 resection during OLS and LLS. [ABSTRACT FROM AUTHOR]

Neutrophils are the most abundant white blood cell in the body and are key participants in the defense against fungal infections. Fungal infections occur often in patients with cirrhosis and are associated with increased 30‐day and 90‐day mortality. Previous studies have shown that specific neutrophil functions are abnormal in patients with cirrhosis, although the extent of neutrophil dysfunction is not well understood. We tested the ability of neutrophils from 21 hospitalized patients with cirrhosis and 23 healthy control patients to kill Candida albicans, a common fungal pathogen in patients with cirrhosis. Using an assay, we also measured the ability of neutrophils to coordinate multicellular, synchronized control of C. albicans hyphae through a process known as swarming. We found that neutrophils from patients with cirrhosis have significantly decreased fungicidal capacity compared with healthy control neutrophils (53% vs. 74%, P < 0.0001) and diminished ability to control hyphal growth normalized as a ratio to healthy control (0.22 vs. 0.65, P < 0.0001). Moreover, serum from patients with cirrhosis decreases the ability of healthy control neutrophils to kill C. albicans (from 60% to 41%, P < 0.003). Circulating concentration of the inflammatory cytokines tumor necrosis factor α, interleukin‐6, and interleukin‐8 were found to be significantly elevated in patients with cirrhosis compared to healthy controls. Following pretreatment with granulocyte‐colony stimulating factor and granulocyte‐macrophage colony‐stimulating factor, neutrophil function was restored to almost that of healthy controls. Conclusion: Our data establish profound neutrophil dysfunction against, and altered swarming to, C. albicans in patients with cirrhosis. This dysfunction can be partially reversed with cytokine augmentation ex vivo. [ABSTRACT FROM AUTHOR]

Objective: To compare the learning curves of the self-taught "pioneers" of laparoscopic liver surgery (LLS) with those of the trained "early adopters" in terms of short- and medium-term patient outcomes to establish if the learning curve can be reduced with specific training. Summary of Background Data: It is expected that a wider adoption of a laparoscopic approach to liver surgery will be seen in the next few years. Current guidelines stress the need for an incremental, stepwise progression through the learning curve in order to minimize harm to patients. Previous studies have examined the learning curve in Stage 2 of the IDEAL paradigm of surgical innovation; however, LLS is now in stage 3 with specific training being provided to surgeons. Methods: Using risk-adjusted cumulative sum analysis, the learning curves and short- and medium-term outcomes of 4 "pioneering" surgeons from stage 2 were compared with 4 "early adapting" surgeons from stage 3 who had received specific training for LLS. Results: After 46 procedures, the short- and medium-term outcomes of the "early adopters" were comparable to those achieved by the "pioneers" following 150 procedures in similar cases. Conclusions: With specific training, "early adapting" laparoscopic liver surgeons are able to overcome the learning curve for minor and major liver resections faster than the "pioneers" who were self-taught in LLS. The findings of this study are applicable to all surgical specialties and highlight the importance of specific training in the safe expansion of novel surgical practice. [ABSTRACT FROM AUTHOR]

Objective: To investigate the risk factors for conversion during laparoscopic liver resection and its effect on patient outcome in a large cohort of patients. Additional analysis of outcomes in patients who required conversion for unfavorable intraoperative findings and conversion for unfavorable intraoperative events will be performed to establish if the cause of conversion effects outcome. Summary Background Data: Multiple previous studies demonstrate that laparoscopic liver surgery reduces intraoperative blood loss, hospital stay, and morbidity while maintaining comparable oncological and survival outcomes when compared with open liver resections. However, limited information is available regarding the possible sequelae of conversion to open surgery, especially with regards to cause of conversion. Methods: A retrospective analysis of 2861 cases from prospectively maintained databases of 7 tertiary liver centers across Europe was performed. Results: Neo-adjuvant chemotherapy, previous liver resection(s), resections for malignant lesions, postero-superior location, and the extent of the resection are associated with an increased risk of conversion. Patients who require conversion have longer operations with higher blood loss; a longer HDU and total hospital stay, increased frequency and severity of complications and higher 30- and 90-day mortality. Patients who had an elective conversion for an unfavorable intraoperative finding had better outcomes than patients who had an emergency conversion secondary to an unfavorable intraoperative event in terms of HDU and total hospital stay, severity of complication, and 90-day mortality. Conclusions: Our study highlights the risk factors for conversion and suggests that conversion for unfavorable intraoperative events is associated with worse outcomes. [ABSTRACT FROM AUTHOR]

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Objectives: The presence of a donor-specific positive crossmatch has been considered to be a contraindication to kidney transplantation because of the risk of hyperacute rejection. Desensitization is the process of removing hazardous preformed donor-specific antibody (DSA) in order to safely proceed with transplant. Traditionally, this involves plasmapheresis and intravenous immune globulin treatments that occur over days to weeks, and has been feasible when there is a living donor and the date of the transplant is known, allowing time for pre-emptive treatments. For sensitized patients without a living donor, transplantation has been historically difficult. Summary of Background Data: IdeS (imlifidase) is an endopeptidase derived from Streptococcus pyogenes which has specificity for human IgG, and when infused intravenously results in rapid cleavage of IgG. Methods: Here we present our single-center's experience with 7 highly sensitized (cPRA98-100%) kidney transplant candidates who had DSA resulting in positive crossmatches with their donors (5 deceased, 2 living) who received IdeS within 24 hours prior to transplant. Results: All pre-IdeS crossmatches were positive and would have been prohibitive for transplantation. All crossmatches became negative post-IdeS and the patients underwent successful transplantation. Three patients had DSA rebound and antibody-mediated rejection, which responded to standard of care therapies. Three patients had delayed graft function, which ultimately resolved. No serious adverse events were associated with IdeS. All patients have functioning renal allografts at a median follow-up of 235 days. Conclusion: IdeS may represent a groundbreaking new method of desensitization for patients who otherwise might have no hope for receiving a lifesaving transplant. [ABSTRACT FROM AUTHOR]

Objective: The European Guidelines Meeting on Laparoscopic Liver Surgery was held in Southampton on February 10 and 11, 2017 with the aim of presenting and validating clinical practice guidelines for laparoscopic liver surgery. Background: The exponential growth of laparoscopic liver surgery in recent years mandates the development of clinical practice guidelines to direct the speciality's continued safe progression and dissemination. Methods: A unique approach to the development of clinical guidelines was adopted. Three well-validated methods were integrated: the Scottish Intercollegiate Guidelines Network methodology for the assessment of evidence and development of guideline statements; the Delphi method of establishing expert consensus, and the AGREE II-GRS Instrument for the assessment of the methodological quality and external validation of the final statements. Results: Along with the committee chairman, 22 European experts; 7 junior experts and an independent validation committee of 11 international surgeons produced 67 guideline statements for the safe progression and dissemination of laparoscopic liver surgery. Each of the statements reached at least a 95% consensus among the experts and were endorsed by the independent validation committee. Conclusion: The European Guidelines Meeting for Laparoscopic Liver Surgery has produced a set of clinical practice guidelines that have been independently validated for the safe development and progression of laparoscopic liver surgery. The Southampton Guidelines have amalgamated the available evidence and a wealth of experts' knowledge taking in consideration the relevant stakeholders' opinions and complying with the international methodology standards. [ABSTRACT FROM AUTHOR]

Objective: To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. Background: Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. Methods: We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). Results: Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03–1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06–2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30–1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79–1.19, P = 0.80; P for interaction = 0.001). Conclusions: Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the perioperative and oncological outcomes of laparoscopic and open liver resection for colorectal liver metastases in the elderly. Background: Laparoscopic liver resection has been associated with less morbidity and similar oncological outcomes to open liver resection for colorectal liver metastases (CRLMs). It has been reported that these benefits continue to be observed in elderly patients. However, in previous studies, patients over 70 or 75 years were considered as a single, homogenous population raising questions regarding the true impact of the laparoscopic approach on this diverse group of elderly patients. Method: Prospectively maintained databases of all patients undergoing liver resection for CRLM in 5 tertiary liver centers were included. Those over 70-years old were selected for this study. The cohort was divided in 3 subgroups based on age. A comparative analysis was performed after the implementation of propensity score matching on the 2 main cohorts (laparoscopic and open groups) and also on the study subgroups. Results: A total of 775 patients were included in the study. After propensity score matching 225 patients were comparable in each of the main groups. Lower blood loss (250 vs 400 mL, P = 0.001), less overall morbidity (22% vs 39%, P = 0.001), shorter High Dependency Unit (2 vs. 6 days, P = 0.001), and total hospital stay (5 vs. 8 days, P = 0.001) were observed after laparoscopic liver resection. Comparable rates of R0 resection (88% vs 88%, P = 0.999), median recurrence-free survival (33 vs 27 months, P = 0.502), and overall survival (51 vs 45 months, P = 0.671) were observed. The advantages seen with the laparoscopic approach were reproduced in the 70 to 74-year old subgroup; however there was a gradual loss of these advantages with increasing age. Conclusions: In patients over 70 years of age laparoscopic liver resection, for colorectal liver metastases, offers significant lower morbidity, and a shorter hospital stay with comparable oncological outcomes when compared with open liver resection. However, the benefits of the laparoscopic approach appear to fade with increasing age, with no statistically significant benefits in octogenarians except for a lower High Dependency Unit stay. [ABSTRACT FROM AUTHOR]

Objective: To examine our pilot to transplant selected patients with acute alcoholic hepatitis, initiated in October 2012. Background: Six months of alcohol abstinence is typically required before liver transplant. A Franco-Belgian protocol showed that early transplant in severe alcoholic hepatitis could improve survival with low incidence of alcohol relapse. Application of this controversial indication is growing despite unclear generalizability. Methods: Data was collected on all patients with alcohol-related liver disease since initiation of the pilot through June 2015. Patients were stratified into two groups: severe alcoholic hepatitis as first liver decompensation (Group 1), alcoholic cirrhosis with ≥6 months abstinence (Group 2). Alcohol relapse was defined as any evidence of alcohol consumption after transplant, which was assessed for harmful patterns of binge or frequent drinking. Results: Forty-three patients underwent liver transplant, including 17 patients in Group 1. Six-month survival was 100% versus 89% for Groups 1 and 2, respectively (P = 0.27). Alcohol relapse was similar in Group 1 versus Group 2: 23.5% versus 29.2% (P > 0.99). Harmful drinking was higher in Group 1 versus Group 2, despite lack of statistical significance: 23.5% versus 11.5% (P = 0.42). Conclusions: In this pilot with carefully selected patients, early liver transplant provided excellent short-term survival, and similar rates of alcohol relapse compared with patients with 6 months of abstinence. Harmful patterns of relapse remain challenging in this population, highlighting the need for validated models to predict alcohol relapse, and need for extreme caution in selecting patients for this exceptional indication. Larger prospective studies and longer follow up are necessary. [ABSTRACT FROM AUTHOR]