Right Ex-situ split grafts for adult liver transplantation - A Multicenter Benchmarking Analysis.

OBJECTIVE: To analyse outcomes after adult right ex-situ split graft liver transplantations (RSLT) and compare with available outcome benchmarks from whole liver transplantation (WLT). SUMMARY BACKGROUND DATA: Ex-situ SLT may be a valuable strategy to tackle the increasing graft shortage. Recently established outcome benchmarks in WLT offer a novel reference to perform a comprehensive analysis of results after ex-situ RSLT. METHODS: This retrospective multicenter cohort study analyzes all consecutive adult SLT performed using right ex-situ split grafts from 01.01.2014 to 01.06.2022. Study endpoints included 1 year graft and recipient survival, overall morbidity expressed by the comprehensive complication index (CCI©) and specific post-LT complications. Results were compared to the published benchmark outcomes in low-risk adult WLT scenarii. RESULTS: In 224 adult right ex-situ SLT, 1y recipient and graft survival rates were 96% and 91.5%, within the WLT benchmarks. The 1y overall morbidity was also within the WLT benchmark (41.8 CCI points vs. <42.1). Detailed analysis, revealed cut surface bile leaks (17%, 65.8% Grade IIIa) as a specific complication without a negative impact on graft survival. There was a higher rate of early hepatic artery thrombosis (HAT) after SLT, above the WLT benchmark (4.9% vs. ≤4.1%), with a significant impact on early graft but not patient survival. CONCLUSION: In this multicentric study of right ex-situ split graft LT, we report 1-year overall morbidity and mortality rates within the published benchmarks for low-risk WLT. Cut surface bile leaks and early HAT are specific complications of SLT and should be acknowledged when expanding the use of ex-situ SLT.

CRISPR and CRISPR-MVLST reveal conserved spacer distribution and high similarity among Salmonella enterica serovar Infantis genomes from Brazil and other countries.

Salmonella enterica serovar Infantis (S. Infantis) is a globally distributed non-typhoid serovar infecting humans and food-producing animals. Considering the zoonotic potential and public health importance of this serovar, strategies to characterizing, monitor and control this pathogen are of great importance. This study aimed to determine the genetic relatedness of 80 Brazilian S. Infantis genomes in comparison to 40 non-Brazilian genomes from 14 countries using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-Multi-Locus Virulence Sequence Typing (CRISPR-MVLST). CRISPR spacers were searched using CRISPR-Cas++ and fimH and sseL alleles using BLAST and MEGA X. Results were analyzed using BioNumerics 7.6 in order to obtain similarity dendrograms. A total of 23 CRISPR1 and 11 CRISPR2 alleles formed by 37 and 26 types of spacers, respectively, were detected. MVLST revealed the presence of five fimH and three sseL alleles. CRISPR's similarity dendrogram showed 32 strain subtypes, with an overall similarity ≥ 78.6. The CRISPR-MVLST similarity dendrogram showed 37 subtypes, with an overall similarity ≥ 79.2. In conclusion, S. Infantis strains isolated from diverse sources in Brazil and other countries presented a high genetic similarity according to CRISPR and CRISPR-MVLST, regardless of their source, year, and/or place of isolation. These results suggest that both methods might be useful for molecular typing S. Infantis strains using WGS data.

Intraoperative indocyanine green fluorescence imaging to predict early hepatic arterial complications after liver transplantation.

The purpose of this study was to propose an innovative intraoperative criterion in a liver transplantation setting that would judge arterial flow abnormality that may lead to early hepatic arterial occlusion, that is, thrombosis or stenosis, when left untreated and to carry out reanastomosis. After liver graft implantation, and after ensuring that there is no abnormality on the Doppler ultrasound (qualitative and quantitative assessment), we intraoperatively injected indocyanine green dye (0.01 mg/Kg), and we quantified the fluorescence signal at the graft pedicle using ImageJ software. From the obtained images of 89 adult patients transplanted in our center between September 2017 and April 2019, we constructed fluorescence intensity curves of the hepatic arterial signal and examined their relationship with the occurrence of early hepatic arterial occlusion (thrombosis or stenosis). Early hepatic arterial occlusion occurred in 7 patients (7.8%), including 3 thrombosis and 4 stenosis. Among various parameters of the flow intensity curve analyzed, the ratio of peak to plateau fluorescence intensity and the jagged wave pattern at the plateau phase were closely associated with this dreaded event. By combining the ratio of peak to plateau at 0.275 and a jagged wave, we best predicted the occurrence of early hepatic arterial occlusion and thrombosis, with sensitivity/specificity of 0.86/0.98 and 1.00/0.94, respectively. Through a simple composite parameter, the indocyanine green fluorescence imaging system is an additional and promising intraoperative modality for identifying recipients of transplant at high risk of developing early hepatic arterial occlusion. This tool could assist the surgeon in the decision to redo the anastomosis despite normal Doppler ultrasonography.

Complex Hepatectomy Under Total Vascular Exclusion of the Liver Preserving the Caval Flow with Portal Hypothermic Perfusion and Temporary Portacaval Shunt: A Proof of Concept.

BACKGROUND: Hypothermic liver perfusion decreases ischemia/reperfusion injury during hepatectomy under standard total vascular exclusion (TVE) of the liver. This surgery needs venovenous bypass and is hampered by high morbi-mortality. TVE preserving the inferior vena cava (IVC) flow is hemodynamically well tolerated but remains limited in duration when performed under liver normothermia. The objective of this study was to report the results of TVE preserving the caval flow, modified to allow hypothermic liver perfusion and obviate splanchnic congestion. PATIENTS AND METHODS: The technique, indicated for tumors abutting large tributaries of the hepatic veins but sparing their roots in IVC and the latter, was applied when TVE was anticipated to last for ≥ 60 min. It combines continuous TVE preserving the IVC flow with hypothermic liver perfusion and temporary portacaval shunt (PCS). Results are given as median (range). RESULTS: Vascular control was achieved in 13 patients with excellent hemodynamical tolerance. PCS was direct or via an interposed synthetic graft (five and eight cases, respectively). Liver temperature dropped to 16.5 (6-24) °C under perfusion of 2 (2-4) L of cold perfusate. TVE lasted 67 (54-125) min and 4.5 (0-8) blood units were transfused. Resection was major in nine cases and was complete in all cases. Five complications occurred in four patients, and the 90-day mortality rate was zero. CONCLUSIONS: This technique maintains stable hemodynamics and combines the advantages of in situ or ex situ standard TVE with hypothermic liver perfusion, without their inherent prolongation of ischemia time and need for venovenous bypass.

Insights into the genomic traits of Yersinia frederiksenii, Yersinia intermedia and Yersinia kristensenii isolated from diverse sources in Brazil.

Yersinia is an important genus comprising foodborne, zoonotic and pathogenic bacteria. On the other hand, species of the so-called group Yersinia enterocolitica-like are understudied and mostly characterized as non-pathogenic, despite of some reports of human infections. The present study aimed to provide genomic insights of Yersinia frederiksenii (YF), Yersinia intermedia (YI) and Yersinia kristensenii (YK) isolated worldwide. A total of 22 YF, 20 YI and 14 YK genomes were searched for antimicrobial resistance genes, plasmids, prophages, and virulence factors. Their phylogenomic relatedness was analyzed by Gegenees and core-genome multi-locus sequence typing. Beta-lactam resistance gene blaTEM-116 and five plasmids replicons (pYE854, ColRNAI, ColE10, Col(pHAD28) and IncN3) were detected in less than five genomes. A total of 59 prophages, 106 virulence markers of the Yersinia genus, associated to adherence, antiphagocytosis, exoenzymes, invasion, iron uptake, proteases, secretion systems and the O-antigen, and virulence factors associated to other 20 bacterial genera were detected. Phylogenomic analysis revealed high inter-species distinction and four highly diverse YF clusters. In conclusion, the results obtained through the analyses of YF, YI and YK genomes suggest the virulence potential of these strains due to the broad diversity and high frequency of prophages and virulence factors found. Phylogenetic analyses were able to correctly distinguish these closely related species and show the presence of different genetic subgroups. These data contributed for a better understanding of YF, YI and YK virulence-associated features and global genetic diversity, and reinforced the need for better characterization of these Y. enterocolitica-like species considered non-pathogenic.

Genomic analysis of a cAmpC (CMY-41)-producing Citrobacter freundii ST64 isolated from patient.

Antibiotic resistance in Citrobacter freundii is a public health concern. This study evaluated the closed genome of a C. freundii isolated from the stool of a hospitalized patient initially related to a Salmonella outbreak. Confirmation of the isolate was determined by whole-genome sequencing. Nanopore sequencing was performed using a MinION with a Flongle flow cell. Assembly using SPAdes and Unicycler yielded a closed genome annotated by National Center for Biotechnology Information Prokaryotic Genome Annotation Pipeline. Genomic analyses employed MLST 2.0, ResFinder4.1, PlasmidFinder2.1, and VFanalyzer. Phylogenetic comparison utilized the Center for Food Safety and Applied Nutrition (CFSAN)-single nucleotide polymorphism pipeline and Genetic Algorithm for Rapid Likelihood Inference. Antimicrobial susceptibility was tested by broth microdilution following Clinical and Laboratory Standards Institute criteria. Multi-locus sequence type in silico analysis assigned the C. freundii as sequence type 64 and the blaCMY-41 gene was detected in resistome investigation. The susceptibility to antibiotics, determined using Sensititre® plates, revealed resistance to aztreonam, colistin, cefoxitin, amoxicillin/clavulanic acid, sulfisoxazole, ampicillin, and streptomycin. The genetic relatedness of the C. freundii CFSAN077772 with publicly available C. freundii genomes revealed a close relationship to a C. freundii SRR1186659, isolated in 2009 from human stool in Tanzania. In addition, C. freundii CFSAN077772 is nested in the same cluster with C. freundii clinical strains isolated in Denmark, Mexico, Myanmar, and Canada, suggesting a successful intercontinental spread.

International Hepato-Pancreato-Billiary Association (IHPBA) registry study on COVID-19 infections in HPB surgery patients.

BACKGROUND: In response to the pandemic, the International Hepato-Pancreato-Biliary Association (IHPBA) developed the IHPBA-COVID Registry to capture data on HPB surgery outcomes in COVID-positive patients prior to mass vaccination programs. The aim was to provide a tool to help members gain a better understanding of the impact of COVID-19 on patient outcomes following HPB surgery worldwide. METHODS: An online registry updated in real time was disseminated to all IHPBA, E-AHPBA, A-HPBA and A-PHPBA members to assess the effects of the pandemic on the outcomes of HPB procedures, perioperative COVID-19 management and other aspects of surgical care. RESULTS: One hundred twenty-five patients from 35 centres in 18 countries were included. Seventy-three (58%) patients were diagnosed with COVID-19 preoperatively. Operative mortality after pancreaticoduodenectomy and major hepatectomy was 28% and 15%, respectively, and 2.5% after cholecystectomy. Postoperative complication rates of pancreatic procedures, hepatic interventions and biliary interventions were respectively 80%, 50% and 37%. Respiratory complication rates were 37%, 31% and 10%, respectively. CONCLUSION: This study reveals a high risk of mortality and complication after HPB surgeries in patient infected with COVID-19. The more extensive the procedure, the higher the risk. Nonetheless, an increased risk was observed across all types of interventions, suggesting that elective HPB surgery should be avoided in COVID positive patients, delaying it at distance from the viral infection.

A multicenter randomized-controlled trial of hypothermic oxygenated perfusion (HOPE) for human liver grafts before transplantation.

BACKGROUND & AIMS: Machine perfusion is a novel method intended to optimize livers before transplantation. However, its effect on morbidity within a 1-year period after transplantation has remained unclear. METHODS: In this multicenter controlled trial, we randomly assigned livers donated after brain death (DBD) for liver transplantation (LT). Livers were either conventionally cold stored (control group), or cold stored and subsequently treated by 1-2 h hypothermic oxygenated perfusion (HOPE) before implantation (HOPE group). The primary endpoint was the occurrence of at least one post-transplant complication per patient, graded by the Clavien score of ≥III, within 1-year after LT. The comprehensive complication index (CCI), laboratory parameters, as well as duration of hospital and intensive care unit stay, graft survival, patient survival, and biliary complications served as secondary endpoints. RESULTS: Between April 2015 and August 2019, we randomized 177 livers, resulting in 170 liver transplantations (85 in the HOPE group and 85 in the control group). The number of patients with at least one Clavien ≥III complication was 46/85 (54.1%) in the control group and 44/85 (51.8%) in the HOPE group (odds ratio 0.91; 95% CI 0.50-1.66; p = 0.76). Secondary endpoints were also not significantly different between groups. A post hoc analysis revealed that liver-related Clavien ≥IIIb complications occurred less frequently in the HOPE group compared to the control group (risk ratio 0.26; 95% CI 0.07-0.77; p = 0.027). Likewise, graft failure due to liver-related complications did not occur in the HOPE group, but occurred in 7% (6 of 85) of the control group (log-rank test, p = 0.004, Gray test, p = 0.015). CONCLUSIONS: HOPE after cold storage of DBD livers resulted in similar proportions of patients with at least one Clavien ≥III complication compared to controls. Exploratory findings suggest that HOPE decreases the risk of severe liver graft-related events. IMPACT AND IMPLICATIONS: This randomized controlled phase III trial is the first to investigate the impact of hypothermic oxygenated perfusion (HOPE) on cumulative complications within a 12-month period after liver transplantation. Compared to conventional cold storage, HOPE did not have a significant effect on the number of patients with at least one Clavien ≥III complication. However, we believe that HOPE may have a beneficial effect on the quantity of complications per patient, based on its application leading to fewer severe liver graft-related complications, and to a lower risk of liver-related graft loss. The HOPE approach can be applied easily after organ transport during recipient hepatectomy. This appears fundamental for wide acceptance since concurring perfusion technologies need either perfusion at donor sites or continuous perfusion during organ transport, which are much costlier and more laborious. We conclude therefore that the post hoc findings of this trial should be further validated in future studies.

Genomic analyses of drug-resistant Salmonella enterica serovar Heidelberg strains isolated from meat and related sources between 2013 and 2017 in the south region of Brazil.

Salmonella enterica serovar Heidelberg (S. Heidelberg) is a zoonotic, ubiquitous, and worldwide-distributed pathogen, responsible for gastroenteritis in humans caused by the consumption of contaminated food. In this study, 11 S. Heidelberg strains isolated from chicken and bovine meat, drag swab, and animal feed between 2013 and 2017 in states of the southern region of Brazil were characterized by whole-genome sequencing (WGS) analyses. Antimicrobial resistance against 18 antimicrobials was determined by disk-diffusion and ciprofloxacin's minimum inhibitory concentration by Etest®. The search for resistance and virulence genes, plasmids, Salmonella Pathogenicity Islands (SPIs) plus multi-locus sequence typing (MLST), and single-nucleotide polymorphisms (SNPs) analyses was conducted using WGS data. All strains harbored resistance genes fosA7, aac(6')-Iaa, sul2, tet(A), blaCMY-2, mdsA, and mdsB, and point mutations in gyrA and parC. All strains showed a phenotypic multidrug-resistant profile, with resistant or intermediate resistant profiles against 14 antimicrobials tested. Plasmids ColpVC, IncC, IncX1, and IncI1-I(Alpha) were detected. Virulence genes related to adherence, macrophage induction, magnesium uptake, regulation, and type III secretion systems plus 10 SPIs were detected. All strains were assigned to ST15 and belonged to two SNP clusters showing high similarity to isolates from the United Kingdom, Chile, Germany, the Netherlands, China, South Africa, and South Korea. In conclusion, the presence of multidrug-resistant S. Heidelberg strains in Brazil showing a global genomic relationship may alert for the necessity of stronger surveillance measures by food safety and public health authorities to limit its spread to humans and animals through foods.

Prospective Genomic Surveillance Reveals Cryptic MRSA Outbreaks with Local to International Origins among NICU Patients.

Methicillin-resistant Staphylococcus aureus (MRSA) infections cause substantive morbidity and mortality in neonates. Using publicly available resources from the National Center of Biotechnology Information (NCBI) and Food and Drug Administration's (FDA) GalaxyTrakr pipeline, we illustrate the dynamics of MRSA colonization and infection in neonates. Over 217 days of prospective surveillance, analyses revealed concurrent MRSA transmission chains affecting 11 of 17 MRSA-colonized patients (65%), with two clusters that demonstrated intervals of more than a month among the appearance of isolates. All MRSA infected neonates (n = 3) showed previous colonization with the infecting strain. GalaxyTrakr clustering of the NICU strains, in the context of 21,521 international isolates deposited in NCBI's Pathogen Detection Resource, revealed NICU isolates to be distinct from adult MRSA strains seen locally and internationally. Clustering of the NICU strains within an international context enhanced the resolution of strain clusters and supported the rule-out of suspected, local transmission events within the NICU. Analyses also identified sequence type 1535 isolates, emergent in the Middle East, carrying a unique SCCmec with fusC and aac(6')-Ie/aph(2'')-1a that provided a multidrug-resistant phenotype. NICU genomic pathogen surveillance, leveraging public repositories and outbreak detection tools, supports rapid identification of cryptic MRSA clusters, and can inform infection prevention interventions for this vulnerable patient population. Results demonstrate that sporadic infections in the NICU may be indicative of hidden chains of asymptomatic transmission best identified with sequenced-based approaches.

Enhanced biofilm and extracellular matrix production by chronic carriage versus acute isolates of Salmonella Typhi.

Salmonella Typhi is the primary causative agent of typhoid fever; an acute systemic infection that leads to chronic carriage in 3-5% of individuals. Chronic carriers are asymptomatic, difficult to treat and serve as reservoirs for typhoid outbreaks. Understanding the factors that contribute to chronic carriage is key to development of novel therapies to effectively resolve typhoid fever. Herein, although we observed no distinct clustering of chronic carriage isolates via phylogenetic analysis, we demonstrated that chronic isolates were phenotypically distinct from acute infection isolates. Chronic carriage isolates formed significantly thicker biofilms with greater biomass that correlated with significantly higher relative levels of extracellular DNA (eDNA) and DNABII proteins than biofilms formed by acute infection isolates. Importantly, extracellular DNABII proteins include integration host factor (IHF) and histone-like protein (HU) that are critical to the structural integrity of bacterial biofilms. In this study, we demonstrated that the biofilm formed by a chronic carriage isolate in vitro, was susceptible to disruption by a specific antibody against DNABII proteins, a successful first step in the development of a therapeutic to resolve chronic carriage.

Open Versus Laparoscopic Right Hepatectomy for Hepatocellular Carcinoma Following Sequential TACE-PVE: A Multicentric Comparative Study.

BACKGROUND: Right hepatectomy (RH) for hepatocellular carcinoma (HCC) is ideally preceded by transcatheter arterial chemoembolization (TACE) and portal vein embolization (PVE). Laparoscopic approach improves short-term outcome and textbook outcome (TO), which reflects the "ideal" surgical outcome, after RH. However, laparoscopic RH on an underlying diseased liver and after TACE/PVE remains a challenging procedure. The aim of this study was to compare the outcomes in patients who underwent laparoscopic liver resection (LLR) or open liver resection (OLR) following TACE/PVE. PATIENTS AND METHODS: All patients with HCC who underwent RH after TACE/PVE in five French centers were retrospectively included. Outcomes were compared between the LLR group and the OLR group using propensity score matching (PSM). Quality of surgical care was defined by TO. RESULTS: Between 2005 and 2019, 117 patients were included (41 in LLR group, 76 in OLR group). Overall morbidity was comparable (51% versus 53%, p = 0.24). In LLR group, TO was completed in 66% versus 37% in OLR group (p = 0.02). LLR and absence of clamping were the only factors associated with TO completion [hazard ratio (HR) 4.27, [1.77-10.28], p = 0.001]. After PSM, 5-year overall survival (OS) and progression-free survival (PFS) were 55% in matched LLR versus 77% in matched OLR, p = 0.35, and 13% in matched LLR versus 17% in matched OLR, p = 0.97. TO completion was independently associated with a better 5-year OS (65.2% versus 42.5%, p = 0.007). CONCLUSION: Major LLR after TACE/PVE should be considered as a valuable option in expert centers to increase the chance of TO, the latter being associated with a better 5-year OS.

Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study.

BACKGROUND: The role of positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients. METHODS: Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated. RESULTS: Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (N.=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/mL with 18F-FDG or 18F-Choline N status significantly impacted DFS (P<0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/mL provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, P<0.05). CONCLUSIONS: The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.

Genomic and phylogenetic analysis of Salmonella enterica serovar Enteritidis strains linked to multiple outbreaks in Brazil.

Salmonella enterica subsp. enterica serovar Enteritidis (SE) has become the prevalent serovar isolated from gastroenteritis cases in Brazil since the 1990s. To better understand the genomic diversity and phylogenetic relationship amongst SE epidemic isolates from Brazil, 30 SE isolates from a variety of implicated foods and case patients of outbreaks between 1999 and 2006 were selected for genome comparison analyses. SE genomes were also compared against publicly available Brazilian SE isolates from pre- and postepidemic period. MLST analysis revealed that all isolates belong to sequence type (ST) 11. A total of seven Salmonella pathogenicity islands (SPIs) (SPI-1, SPI-3-5, SPI-13, SPI14, and C63PI) were identified in the evaluated genomes and all studied SE genomes carried similar prophage profiling. Resistome analysis revealed the presence of resistance genes to aminoglycosides [aac(6')laa, aph(3")-lb, aph(6)-ld], as well as point mutations in gyrA. Phylogenetic analysis demonstrated that certain isolates have circulated in Brazil for years and been involved in distinct outbreaks.

Genomic analysis of Listeria monocytogenes from US food processing environments reveals a high prevalence of QAC efflux genes but limited evidence of their contribution to environmental persistence.

BACKGROUND: Quaternary ammonium compound (QAC) efflux genes increase the minimum inhibitory concentration of Listeria monocytogenes (Lm) to benzalkonium chloride sanitizer, but the contribution of these genes to persistence in food processing environments is unclear. The goal of this study was to leverage genomic data and associated metadata for 4969 Lm isolates collected between 1999 and 2019 to: (1) evaluate the prevalence of QAC efflux genes among Lm isolates from diverse US food processors, (2) use comparative genomic analyses to assess confounding factors, such as clonal complex identity and stress tolerance genotypes, and (3) identify patterns in QAC efflux gene gain and loss among persistent clones within specific facilities over time. RESULTS: The QAC efflux gene cassette bcrABC was present in nearly half (46%) of all isolates. QAC efflux gene prevalence among isolates was associated with clonal complex (𝛘2 < 0.001) and clonal complex was associated with the facility type (𝛘2 < 0.001). Consequently, changes in the prevalence of QAC efflux genes within individual facilities were generally attributable to changes in the prevalence of specific clonal complexes. Additionally, a GWAS and targeted BLAST search revealed that clonal complexes with a high prevalence of QAC efflux genes commonly possessed other stress tolerance genes. For example, a high prevalence of bcrABC in a clonal complex was significantly associated with the presence of the SSI-1 gene cluster (p < 0.05). QAC efflux gene gain and loss were both observed among persistent populations of Lm in individual facilities, suggesting a limited direct role for QAC efflux genes as predictors of persistence. CONCLUSION: This study suggests that although there is evidence that QAC efflux genes are part of a suite of adaptations common among Lm isolated from some food production environments, these genes may be neither sufficient nor necessary to enhance persistence. This is a crucial distinction for decision making in the food industry. For example, changes to sanitizer regimen targeting QAC tolerance would not address other contributing genetic or non-genetic factors, such as equipment hygienic design which physically mediates sanitizer exposure.

In situ normothermic regional perfusion versus ex situ normothermic machine perfusion in liver transplantation from donation after circulatory death.

In situ normothermic regional perfusion (NRP) and ex situ normothermic machine perfusion (NMP) aim to improve the outcomes of liver transplantation (LT) using controlled donation after circulatory death (cDCD). NRP and NMP have not yet been compared directly. In this international observational study, outcomes of LT performed between 2015 and 2019 for organs procured from cDCD donors subjected to NRP or NMP commenced at the donor center were compared using propensity score matching (PSM). Of the 224 cDCD donations in the NRP cohort that proceeded to asystole, 193 livers were procured, resulting in 157 transplants. In the NMP cohort, perfusion was commenced in all 40 cases and resulted in 34 transplants (use rates: 70% vs. 85% [p = 0.052], respectively). After PSM, 34 NMP liver recipients were matched with 68 NRP liver recipients. The two cohorts were similar for donor functional warm ischemia time (21 min after NRP vs. 20 min after NMP; p = 0.17), UK-Donation After Circulatory Death risk score (5 vs. 5 points; p = 0.38), and laboratory Model for End-Stage Liver Disease scores (12 vs. 12 points; p = 0.83). The incidence of nonanastomotic biliary strictures (1.5% vs. 2.9%; p > 0.99), early allograft dysfunction (20.6% vs. 8.8%; p = 0.13), and 30-day graft loss (4.4% vs. 8.8%; p = 0.40) were similar, although peak posttransplant aspartate aminotransferase levels were higher in the NRP cohort (872 vs. 344 IU/L; p < 0.001). NRP livers were more frequently allocated to recipients suffering from hepatocellular carcinoma (HCC; 60.3% vs. 20.6%; p < 0.001). HCC-censored 2-year graft and patient survival rates were 91.5% versus 88.2% (p = 0.52) and 97.9% versus 94.1% (p = 0.25) after NRP and NMP, respectively. Both perfusion techniques achieved similar outcomes and appeared to match benchmarks expected for donation after brain death livers. This study may inform the design of a definitive trial.

Prevalence and Clonal Diversity of over 1,200 Listeria monocytogenes Isolates Collected from Public Access Waters near Produce Production Areas on the Central California Coast during 2011 to 2016.

A 5-year survey of public access surface waters in an agricultural region of the Central California Coast was done to assess the prevalence of the foodborne pathogen Listeria monocytogenes. In nature, L. monocytogenes lives as a saprophyte in soil and water, which are reservoirs for contamination of preharvest produce. Moore swabs were deployed biweekly in lakes, ponds, streams, and rivers during 2011 to 2016. L. monocytogenes was recovered in 1,224 of 2,922 samples, resulting in 41.9% prevalence. Multiple subtypes were isolated from 97 samples, resulting in 1,323 L. monocytogenes isolates. Prevalence was higher in winter and spring and after rain events in some waterways. Over 84% of the isolates were serotype 4b. Whole-genome sequencing was done on 1,248 isolates, and in silico multilocus sequence typing revealed 74 different sequence types (STs) and 39 clonal complexes (CCs). The clones most isolated, CC639, CC183, and CC1, made up 27%, 19%, and 13%, respectively, of the sequenced isolates. Other types were CC663, CC6, CC842, CC4, CC2, CC5, and CC217. All sequenced isolates contained intact copies of core L. monocytogenes virulence genes, and pathogenicity islands LIPI-3 and LIPI-4 were identified in 73% and 63%, respectively, of the sequenced isolates. The virulence factor internalin A was predicted to be intact in all but four isolates, while genes important for sanitizer and heavy metal resistance were found in <5% of the isolates. These waters are not used for crop irrigation directly, but they are available to wildlife and can flood fields during heavy rains. IMPORTANCE Listeria monocytogenes serotype 4b and 1/2a strains are implicated in most listeriosis, and hypervirulent listeriosis stems from strains containing pathogenicity islands LIPI-3 and LIPI-4. The waters and sediments in the Central California Coast agricultural region contain widespread and diverse L. monocytogenes populations, and all the isolates contain intact virulence genes. Emerging clones CC183 and CC639 were the most abundant clones, and major clones CC1, CC4, and CC6 were well represented. CC183 was responsible for three produce-related outbreaks in the last 7 years. Most of the isolates in the survey differ from those of lesser virulence that are often isolated from foods and food processing plants because they contain genes encoding an intact virulence factor, internalin A, and most did not contain genes for sanitizer and heavy metal resistance. This isolate collection is important for understanding L. monocytogenes populations in agricultural and natural regions.

Impact of the duration of normothermic regional perfusion on the results of liver transplant from controlled circulatory death donors: A retrospective, multicentric study.

In France, the program of controlled donation after circulatory death (cDCD) was established with routine use of in situ normothermic regional perfusion (NRP). There is currently no consensus on its optimal duration. The purpose was to assess the impact of NRP duration on liver graft function and biliary outcomes. One-hundred and fifty-six liver recipients from NRP-cDCD donors from six French centers between 2015 and 2019 were included. Primary endpoint was graft function assessed by early allograft dysfunction (EAD, according to Olthoff's criteria) and MEAF (model for early allograft function) score. Overall, three (1.9%) patients had primary non-function, 30 (19.2%) patients experienced EAD, and MEAF score was 7.3 (±1.7). Mean NRP duration was 179 (±43) min. There was no impact of NRP duration on EAD (170±44 min in patients with EAD vs. 181±42 min in patients without, P = .286). There was no significant association between NRP duration and MEAF score (P = .347). NRP duration did neither impact on overall biliary complications nor on non-anastomotic biliary strictures (overall rates of 16.7% and 3.9%, respectively). In conclusion, duration of NRP in cDCD donors does not seem to impact liver graft function and biliary outcomes after liver transplantation. A 1 to 4-h perfusion represents an optimal time window.

Treatment strategies to resectable metachronous colorectal liver metastases after adjuvant oxaliplatin-based chemotherapy for primary colorectal cancer.

BACKGROUND: outcome of patients who develop resectable metachronous colorectal liver metastases (CLM) after adjuvant oxaliplatin-based chemotherapy for Stage III colorectal cancer (CRC) is not well defined and the value of preoperative chemotherapy is controversial. METHODS: From 2006 to 2013, all patients undergoing liver resection for Class I metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC, across 32 French academic centers, were included. RESULTS: Sixty-two patients with an average of 2 ± 1 CLM were included. Thirty-two (52%) patients received preoperative chemotherapy. There was no significant difference in the characteristics of CLM between patients with or without preoperative chemotherapy. After a median follow-up of 29 months, 3-year overall and disease-free survival rates were 79.8% and 34.6%, respectively. The median disease-free survival was not different in patients with or without preoperative chemotherapy (17 vs. 35 months respectively, p = 0.112). In multivariate analysis, only CEA level > 200 ng/ml was associated with the risk of recurrence (p = 0.027; OR = 4.7, 95% CI = 1.2-18.7). CONCLUSION: Liver resection provides a good outcome in patients with limited metachronous CLM after adjuvant oxaliplatin-based chemotherapy for CRC. The interest of preoperative chemotherapy is not obvious and should be tested in a prospective controlled study.

Subjective Difficulty Scale in Liver Transplantation: A Prospective Observational Study.

The predictive value of a subjective difficulty scale (DS) after surgical procedures is unknown. The objective of this study was to evaluate the prognostic value of a DS after liver transplantation (LT) and to identify predictors of difficulty. Surgeons prospectively evaluated the difficulty of 441 consecutive liver transplantations from donation after brain death at the end of the surgery by using a DS from 0 to 10 ("the easiest to the hardest you can imagine"). DS was associated with severe morbidity. The risk of graft loss at 1 year remained unchanged from 0 to 6 but increased beyond 6. Graft survival and patient survival of group with DS 7-10 was significantly impaired compared to groups with DS: 0-3 or DS: 4-6 but were significantly impaired for the group with DS: 7-10. Independent predictors of difficult LT (DS ≥ 7) were annular segment 1, transjugular intrahepatic portosystemic shunt, retransplantation beyond 30 days, portal vein thrombosis, and ascites. Of them, ascites was a borderline non-significant covariate (p = .04). Vascular complications occurred more often after difficult LT (20.5% vs. 5.9%), whereas there was no difference in the other types of complications. DS can be used to tailor monitoring and anticipate early complications. External validation is needed.