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Liver transplantation (LT) is a complex operation that most transplant surgeons learn in fellowship. Training varies as there is lack of objective data that can be used to standardize teaching. We performed a retrospective review of our adult LT database with aim of looking at fellow's experience. Using American Society of Transplant Surgery cutoff of, at least 45 LT during fellowship, data for first 45 LT were compared to LT 45-90. Fellow's cases were also clustered in sequential groups of 15 LT and analyzed to estimate the learning curve (LC). Comparison of LT 1-45 with LT 46-90 showed significantly lower total operative times (TOT) (324 vs. 344 min) and warm ischemia times (WIT) (28 vs. 31 min) in the 45-90 group. Rates of biliary complications (23.8% vs. 16.4%) and bile leaks alone (10.3% vs. 5.5%) were significantly higher for first 45 LT. Analysis of fellows experience in sequential clusters of 15 LT showed decreasing TOT, WIT, biliary complications and rates of unplanned return to the OR with progression of fellowship. This study validates the current ASTS requirement of at least 45 LT. LC generated using these data can help individualize training and optimize outcomes through identification of areas in need of improvement.

Guidelines for surveillance colonoscopy depend on polyp histology. When patients present to a new healthcare system and report a personal history of “colon polyps,” however, information on polyp histology is frequently unavailable. To assess adenoma prevalence in patients with a history of colonic polyps of unknown histology and to compare it to patients undergoing either screening colonoscopy or surveillance colonoscopy for known adenomatous polyps. This cohort study evaluated colonoscopies of patients ≥ 50 years of age over a 14-year period at a single institution. The exposure of interest was colonoscopy indication, categorized into three groups: screening colonoscopy, surveillance colonoscopy for history of colonic polyp(s) of unknown histology, and surveillance colonoscopy for history of adenoma(s). The primary outcome was adenoma detection rate. Multivariable logistic regression was used to assess the association between colonoscopy indication and adenoma detection rate. Of 31,856 colonoscopies, the adenoma prevalence was 26.1% for patients undergoing screening colonoscopy, 32.9% for patients with a history of polyps of unknown histology, and 41.9% for patients with a history of known adenomatous polyps. Relative to screening colonoscopies, there were higher odds of adenoma detection in surveillance colonoscopies for polyps of unknown histology (aOR compared to screening 1.42, 95% CI 1.30–1.55) and even higher odds among surveillance colonoscopies for a history of adenoma (aOR compared to screening 1.89, 95% CI 1.75–2.05). The adenoma prevalence on surveillance colonoscopy for patients with polyps of unknown histology was higher than that of screening colonoscopies but lower than that of surveillance colonoscopies for patients with adenomatous polyps.

Very few antimicrobial agents remain active against Pseudomonas aeruginosa and Klebsiella pneumoniae in some geographic regions. We evaluated the in vitro activity of ceftazidime-avibactam, ceftolozane-tazobactam, and comparator agents against 6,210 P. aeruginosa and 6,041 K. pneumoniae isolates consecutively collected from 85 U.S. medical centers across 37 states in 2016-2018. Antimicrobial susceptibility was determined by reference broth microdilution method. K. pneumoniae isolates found to have elevated MICs for broad-spectrum cephalosporins were submitted to whole-genome sequencing analysis to detect resistance genes. Ceftazidime-avibactam (97.1% susceptible [S]) and ceftolozane-tazobactam (97.0%S) were the most active compounds against P. aeruginosa and retained activity against meropenem-nonsusceptible (88.5-89.0%S), piperacillin-tazobactam-nonsusceptible (86.6-87.0%S), and other resistant subsets of isolates. The most active agents against K. pneumoniae per CLSI criteria were ceftazidime-avibactam (>99.9%S), amikacin (98.4%S), and meropenem (97.1%S). Ceftolozane-tazobactam was active against 95.3% of K. pneumoniae but showed limited activity against extended-spectrum β-lactamase and carbapenemase producers (82.9% and 0.0%S, respectively).

The transition to college is a critical determinant of student success in higher education. Increasingly, students’ parents play a key role in supporting their sons and daughters as they adjust to ...

Hepatoblastoma (HB) is a rare childhood malignancy with hepatic resection (HR) or liver transplantation (LT) providing the best chance of cure. In this study, we analyze the National Cancer Database lacks (NCDB) to compare outcomes following HR and LT for HB. Review of the US experience with surgical (HR and LT) management of pediatric (

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a comprehensive, evidence-based treatment algorithm that includes appropriate treatment options for patients stratified by their eligibility for surgical treatment. The group coined a novel, more inclusive phrase for targeted locoregional tumor treatment (a blanket term for resection, ablation, and other emerging locoregional treatments): local parenchymal tumor destruction therapy. The expert panel proposed new nomenclature for 3 distinct disease categories of liver-dominant metastatic colorectal cancer that is consistent with other tumor types: (I) surgically treatable (resectable); (II) surgically untreatable (borderline resectable); (III) advanced surgically untreatable (unresectable) disease. Patients may present at any point in the algorithm and move between categories depending on their response to therapy. The broad intent of therapy is to transition patients toward individualized treatments where possible, given the survival advantage that resection offers in the context of a comprehensive treatment plan. This article reviews what is known about the role of SIRT with Y-90 as neoadjuvant, definitive, or palliative therapy in these different clinical situations and provides insight into when treatment with SIRT with Y-90 may be appropriate and useful, organized into distinct treatment algorithm steps.

PURPOSE: Postoperative length of stay (PLOS) and readmission rate are pancreatoduodenectomy (PD) outcome measures, which are reported individually but may be interrelated. The purpose of this study was to evaluate how well a composite length of stay measure (CLOS) that included PLOS and readmission length of stay describes outcomes. To do so, we evaluated how well CLOS correlated to postoperative complications absolutely and compared to PLOS. METHODS: A total of 668 PDs performed between 2011 and 2018 were evaluated. CLOS was calculated from PLOS and readmission length of stay. Complication severity was judged by the Modified Accordion Grading System (MAGS). Multinomial logistical regression models (MLRM) were used to investigate the relationship between either PLOS or CLOS and complications. Multilevel and pairwise area under curves (AUC) using SAS macro %MultAUC were provided for both models. RESULTS: A total of 432 of 668 patients (65%) developed complications. One hundred seventy-seven patients (27%) were readmitted. Mean PLOS was 10.2 days (7.1 SD) and mean CLOS was 12.3 days (10.1 SD). PLOS and CLOS both were correlated linearly to MAGS grade. Spearman correlation coefficient for CLOS vs. MAGS of 0.68 was higher than that of 0.49 for PLOS vs. MAGS. Multilevel AUC from MLRM using PLOS was 0.66, but multilevel AUC from MLRM using CLOS was 0.71. DISCUSSION: CLOS provides an accurate estimate of hospital day utilization per patient for PD, reflecting not only the basal hospital recovery time for PD but the added time needed because of readmissions due to complications. It is tightly correlated to number and severity of postoperative complications.

Cholangiocarcinoma is an aggressive malignancy of the extrahepatic bile ducts. Hilar lesions are most common. Patients present with obstructive jaundice and intrahepatic bile duct dilation. Cross-sectional imaging reveals local, regional, and distant extent of disease, with direct cholangiography providing tissue for diagnosis. The consensus of a multidisciplinary committee dictates treatment. Resection of the extrahepatic bile duct and ipsilateral hepatic lobe with or without vascular resection and transplantation after neoadjuvant protocol are options for curative treatment. The goal of surgery is to remove the tumor with negative margins. Patients with inoperable tumors or metastatic disease are best served with palliative chemoradiotherapy.

Background Ischemic stroke provokes a neuroinflammatory response and simultaneously promotes release of epinephrine and norepinephrine by the sympathetic nervous system. This increased sympathetic outflow can act on β2-adrenergic receptors expressed by immune cells such as brain-resident microglia and monocyte-derived macrophages (MDMs), but the effect on post-stroke neuroinflammation is unknown. Thus, we investigated how changes in β2-adrenergic signaling after stroke onset influence the microglia/MDM stroke response, and the specific importance of microglia/MDM β2-adrenergic receptors to post-stroke neuroinflammation. Methods To investigate the effects of β2-adrenergic receptor manipulation on post-stroke neuroinflammation, we administered the β2-adrenergic receptor agonist clenbuterol to mice 3 h after the onset of photothrombotic stroke. We immunostained to quantify microglia/MDM numbers and proliferation and to assess morphology and activation 3 days later. We assessed stroke outcomes by measuring infarct volume and functional motor recovery and analyzed gene expression levels of neuroinflammatory molecules. Finally, we evaluated changes in cytokine expression and microglia/MDM response in brains of mice with selective knockout of the β2-adrenergic receptor from microglia and monocyte-lineage cells. Results We report that clenbuterol treatment after stroke onset causes enlarged microglia/MDMs and impairs their proliferation, resulting in reduced numbers of these cells in the peri-infarct cortex by 1.7-fold at 3 days after stroke. These changes in microglia/MDMs were associated with increased infarct volume in clenbuterol-treated animals. In mice that had the β2-adrenergic receptor specifically knocked out of microglia/MDMs, there was no change in morphology or numbers of these cells after stroke. However, knockdown of β2-adrenergic receptors in microglia and MDMs resulted in increased expression of TNFα and IL-10 in peri-infarct tissue, while stimulation of β2-adrenergic receptors with clenbuterol had the opposite effect, suppressing TNFα and IL-10 expression. Conclusions We identified β2-adrenergic receptor signaling as an important regulator of the neuroimmune response after ischemic stroke. Increased β2-adrenergic signaling after stroke onset generally suppressed the microglia/MDM response, reducing upregulation of both pro- and anti-inflammatory cytokines, and increasing stroke size. In contrast, diminished β2-adrenergic signaling in microglia/MDMs augmented both pro- and anti-inflammatory cytokine expression after stroke. The β2-adrenergic receptor may therefore present a therapeutic target for improving the post-stroke neuroinflammatory and repair process.

Objectives To evaluate the antimicrobial susceptibility patterns of Pseudomonas aeruginosa isolates collected from the lower respiratory tract of cystic fibrosis (CF) patients. Methods We susceptibility tested 273 contemporary P. aeruginosa isolates from 39 hospitals worldwide (17 countries) by the reference broth microdilution method. Results Ceftazidime/avibactam [MIC50/90, 2/8 mg/L; 96.0% susceptible (S)] was the most active agent, followed by ceftolozane/tazobactam (MIC50/90, 1/4 mg/L; 90.5% S), ceftazidime (MIC50/90, 2/>32 mg/L; 80.6% S), piperacillin/tazobactam (MIC50/90, 4/128 mg/L; 80.2% S) and tobramycin (MIC50/90, 2/>16 mg/L; 76.6% S). Ceftazidime/avibactam retained activity against P. aeruginosa isolates non-susceptible to meropenem (86.5% S to ceftazidime/avibactam), piperacillin/tazobactam (85.2% S to ceftazidime/avibactam) or ceftazidime (79.2% S to ceftazidime/avibactam). MDR phenotype was observed among 36.3% of isolates, and 88.9% and 73.7% of MDR isolates were susceptible to ceftazidime/avibactam and ceftolozane/tazobactam, respectively. Against isolates non-susceptible to meropenem, piperacillin/tazobactam and ceftazidime, susceptibility rates were 78.9% for ceftazidime/avibactam and 47.4% for ceftolozane/tazobactam. Ceftazidime/avibactam was active against 65.4% of ceftolozane/tazobactam-non-susceptible isolates and ceftolozane/tazobactam was active against 18.2% of ceftazidime/avibactam-non-susceptible isolates. Conclusions Ceftazidime/avibactam and ceftolozane/tazobactam exhibited potent and broad-spectrum activity against P. aeruginosa isolated from CF patients worldwide, but higher susceptibility rates for ceftazidime/avibactam compared with ceftolozane/tazobactam were observed among the resistant subsets. Ceftazidime/avibactam and ceftolozane/tazobactam represent valuable options to treat CF pulmonary exacerbations caused by P. aeruginosa.

Liver transplantation (LT) offers an effective alternative treatment for unresectable hepatocellular carcinoma (HCC). Despite its growing acceptance and longer life expectancy rates, survival data in older patients are conflicting and consensus guidelines are lacking in terms of a cut-off age range for operations.We explored our prospectively maintained institutional database to identify patients diagnosed with HCC between January 1, 2002 and December 31, 2019. Long-term oncologic outcomes were analyzed in patients undergoing LT or hepatic resection, with patient age considered as the primary variable.In total, 1,629 patients with HCC were identified, of whom 700 were considered for curative operations (LT, n = 538; resection, n = 162). Patients older than 65 years were less likely to be considered for LT (p0.01), although there were no age-related differences in the de-listing rate among age groups (p = 0.90). Older patients had overall survival (OS) outcomes comparable with younger patients after LT (3-year OS: 85.5% vs 84%; 5-year OS: 73.9% vs 77%; p = 0.26). Long-term survival was lower in the group who underwent resection, however, older patients still demonstrated equivalent OS outcomes (3-year OS: 59% vs 64.8%; 5-year OS: 44.8% vs 49%; p = 0.13). There were no differences in the development of local or distant metastatic disease between groups.Although older candidates were less likely to be considered for LT in the management of HCC, judicious matching can lead to OS data comparable with their younger counterparts. Previous age misconceptions need to be challenged without the concern of worse long-term oncologic outcomes after surgery.

The coronavirus disease 2019 (COVID-19) pandemic is a rapidly changing circumstance with dramatic policy changes and universal efforts to deal with the initial crisis and minimize its consequences. To identify changes to organ donation and transplantation during this time, an anonymous web-based survey was distributed to 19 select organ procurement organizations (OPOs) throughout the United States comparing 90-day activity during March-May 2020 and March-May 2019. Seventeen OPOs responded to the survey (response rate of 89.5%). Organ authorization decreased by 11% during the current pandemic (n = 1379 vs n = 1552, P = .0001). Organ recovery for transplantation fell by 17% (P = .0001) with a further 18% decrease in the number of organs transplanted (P = .0001). Donor cause of death demonstrated a 4.5% decline in trauma but a 35% increase in substance abuse cases during the COVID-19 period. All OPOs reported significant modifications in response to the pandemic, limiting the onsite presence of staff and transitioning to telephonic approaches for donor family correspondence. Organ donation during the current climate has seen significant changes and the long-term implications of such shifts remain unclear. These trends during the COVID-19 era warrant further investigation to address unmet needs, plan for a proportionate response to the virus and mitigate the collateral impact.

Background: Combined hepatocellular-cholangiocarcinoma tumors (cHCC-CCA) are a heterogeneous group of rare malignancies that have no established optimal treatment. Patients and Methods: We identified patients with cHCC-CCA treated at a tertiary center and retrospectively examined their histology, interventions, and outcomes. We calculated disease control rate (DCR), disease progression, overall survival, and progression-free survival (PFS) between treatment subgroups. Results: A total of 123 patients were evaluable. Interventions included resection, locoregional therapy, transplant, chemotherapy, and targeted agents. Ultimately, 68 patients received systemic treatment-57 with gemcitabine plus either 5-fluoropyrimidine (5-FU) or a platinum combination. Disease progression was more common in the gemcitabine/5-FU group versus gemcitabine/platinum (P=.028), whereas DCR favored gemcitabine/platinum (78.4% vs 38.5%; P=.0143). Median PFS from time of initial diagnosis favored the gemcitabine/platinum group, but the difference did not reach statistical significance. Targeted agents had minimal to no effect on survival metrics. Conclusions: Gemcitabine/platinum seems to be a superior regimen for patients with cHCC-CCA who require systemic treatment. Further studies are needed to clarify the regimen's efficacy and applicability in patient subgroups.

Research focus in recent years on magnetic behaviour of transition metal (TM) ions embedded in semiconductors has shifted from intrinsic effects to extrinsic effects such as the formation of nanoclusters of the TM ions and the influence of the host matrix on their magnetic behaviour. Our studies, using conversion electron Mossbauer Spectroscopy and magnetization measurements, on SiO2 and Al2O3 substrates implanted with 4 at. % Fe, show ferromagnetic behaviour of α-Fe clusters in amorphous SiO2, but α-Fe2O3 clusters displaying superparamagnetic relaxation in crystalline Al2O3

Background Increasing use of Living Donor Kidney Transplantation (LDKT) would decrease the discrepancy between patients awaiting transplantation and organ availability. Minimally invasive surgical approaches attempt to improve outcomes and foster living donation. This report compares outcomes of open minimal incision nephrectomy (Mini N) and a hand assisted laparoscopic nephrectomy (HALN). Methods This is a retrospective analysis of a prospectively maintained clinical database of LDKT using HALN or Mini N at a single institution between July 2007 and December 2015. Donor and recipient demographics, relevant pre-, intra- and post-operative factors, outcomes such as patient and graft survival rates, and complications were evaluated. Results Four hundred and fifty-four adult LDKT (243 Mini N, 211 HALN) were performed during the study period. Recipient and donor demographics were comparable except for higher BMI (p = 0.027) in HALN donors. One-, 3- and 5-year patient and graft survival rates were comparable. Six HALN donors experienced infectious wound complications or superficial skin dehiscence; none did in the Mini N group (p = 0.009). Eight HALN donors and one Mini N donor required an incisional hernia repair (p = 0.014). Recipients had similar warm ischemia times (33 v. 35 min, p = 0.491), but recipient surgeons of HALN nephrectomies subjectively noted higher anastomotic difficulty (10.4% v. 4.5%, p = 0.0183). Other parameters were similar between groups. Conclusion Both Mini N and HALN provide similar long term recipient and donor outcomes. Offering techniques such as Mini N and HALN for living donor kidney procurement facilitates the opportunity to provide living donors safer and better tolerated nephrectomy procedures.

OBJECTIVE. To use data-logging technology to objectively track and identify predictors of hearing aid (HA) usage and aided sound exposure. STUDY DESIGN. Case series with planned data collection. SETTING. Tertiary academic medical center. SUBJECTS AND METHODS. Individuals with HAs between 2007 and 2016 were included (N = 431; mean, 74.6 years; 95% CI, 73.1–76.0). Data-logging technology intrinsic to new-generation HAs was enabled to track usage and sound exposure. With multivariable linear regression, age, sex, number of audiology visits, duration of audiologic follow-up, pure tone average, and HA side were assessed as predictors of usage (hours/day) and aided sound exposure (dB-hours/day; ie, “dose” of sound per day). RESULTS. Mean follow-up was 319 days (95% CI, 277–360). Mean HA usage was 8.4 hours/day (95% CI, 8.0–8.8; N = 431). Mean aided sound exposure was 440 dB-hours/day (95% CI, 385–493; n = 110). HA use (β < 0.001, P = .45) and aided sound exposure (β = −0.006, P = .87) were both stable over time. HA usage was associated only with hearing loss level (pure tone average; β = 0.030, P = .04). Aided sound exposure was associated only with duration of audiologic follow-up (β = 0.100, P = .02). CONCLUSION. While measurement of HA use has traditionally relied on subjective reporting, data logging offers an objective tool to longitudinally track HA use and sound exposure. We demonstrate the feasibility of using this potentially powerful research tool. Usage and sound exposure were stable among patients throughout the study period. Use was greater among subjects with greater hearing loss. Maximizing aided sound exposure might be possible through continued audiology follow-up visits.

This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients.To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups.Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative.Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff.Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values.Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

BACKGROUND: Medial opening-wedge high tibial osteotomy (HTO) is one of the most common and effective HTO techniques, in which the proximal tibia is cut medially, leaving an intact lateral hinge of bone that can be opened to a variable amount for the desired correction, but the technical complications of lateral cortex fracture and intra-articular fracture are well described. The lateral bone hinge for medial opening-wedge HTO is crucial. If the hinge is too small, the tibia can fracture and become unstable, requiring further fixation. If the hinge is too large, the osteotomy can propagate into the joint as an intra-articular fracture when opening the osteotomy. PURPOSE: We propose a new technique that utilizes digital preoperative templating to improve the accuracy of the cut. Preoperative digital templating may allow the surgeon to reproducibly obtain a lateral bone hinge of 10 mm, while also reducing radiation exposure relative to the traditional fluoroscopically assisted technique. METHODS: Ten cadaver extremities from five cadavers were matched into pairs and randomized into two groups: those with and without preoperative templating. The templating protocol measures the distance between two points on the medial and lateral cortices, and 20 mm is subtracted to determine the depth of the saw cut (10 mm for the hinge and another 10 mm because the proximal tibia is oval in shape). The control method was done by making the cut using fluoroscopy with tactile feedback. Postoperative computed tomography scans were obtained of all legs to measure the width of the lateral bone hinge. Intraoperative fluoroscopy used during both techniques and the numbers of fluoroscopy shots were recorded. RESULTS: We found neither the treatment group with preoperative planning nor the control group with the conventional technique had bone hinge widths that were different from the ideal 10 mm. The average hinge widths for the treatment and control groups were 11.2 and 11.5 mm, respectively. However, the treatment group was exposed to significantly less intraoperative fluoroscopy during the osteotomy cut. The average total number of fluoroscopy shots was 2.2 in the treatment group versus 6.3 for the control group. CONCLUSIONS: This new preoperative planning technique achieves similar accuracy of the lateral bone hinge when compared to current methods but exposes the patient, surgeon, and staff to significantly less intraoperative radiation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11420-017-9591-3) contains supplementary material, which is available to authorized users.

Background Delayed gastric emptying (DGE) is a common serious problem after pancreaticoduodenectomy (PD). Flange gastrojejunostomy (FL-GE) is a previously described technique that creates an internal flange in a hand-sewn gastroenterostomy. Results of FL-GE on incidence and severity of DGE after PD are presented. Study Design Data were extracted from a prospective database of PD. Standard PD with antrectomy were performed with flange gastroenterostomy (FL-GE) or other techniques (NonFL-GE) at a single institution. The International Study Group of Pancreatic Surgery (ISGPS) definition of DGE was used, and DGE severity was graded based on the ISGPS grading system and the Modified Accordion Grading System (MAGS). Results There were 215 standard PDs performed. Sixty-eight (32%) were FL-GE and 147 (68%) were NonFL-GE. Delayed gastric emptying rates in FL-GE and NonFL-GE were 9% and 23%, respectively (p = 0.012). Differences in severity of DGE were even more prominent: 29% of DGEs in the NonFL-GE group were ISGPS grade C vs 0% in FL-GE. Also, 35% of DGEs in the NonFL-GE group were MAGS 3 vs 0% in FL-GE. Because of some differences in sex and inflammatory complications between groups, a propensity score analysis was performed, creating 57 matched patients in the FL-GE and NonFL-GE groups. The incidence of DGE remained significantly different in the groups (5% in FL-GE vs 18% in NonFL-GE; p = 0.039). Conclusions In this cohort study, the flange technique was associated with a marked reduction in the incidence of DGE after PD.

There are two different contexts in the Irish bTB eradication programme in which the interferon-gamma assay (IFN-γ) is applied. Firstly, the IFN-γ assay is applied routinely to high risk cohorts in herds with four or more reactors to the SICTT. The IFN-γ test is then carried out on blood samples submitted to the laboratory within 8 h of collection (diagnostic testing). Secondly, the use of the IFN-γ assay has recently been extended to test SICTT reactors as part of a general quality assurance (QA) scheme to monitor the performance of the SICTT. Blood samples from reactors are tested one day after blood collection (QA testing). In this study, we analysed the relative performance of the SICTT and IFN-γ when used in parallel as an 8 h diagnostic test and as a 24 h QA test on SICTT reactors. A total of 17,725 IFN-γ tests were included in the analysis (11,658 diagnostic tests and 6067 QA tests). Of the samples submitted for diagnostic testing, the proportion positive to IFN-γ decreased with the severity of interpretation of the SICTT result. Of the standard reactors that were tested with IFN-γ in the QA programme, 92.2% were positive to the IFN-γ test. Among animals that were SICTT −ve/IFN-γ +ve, 18.9% were positive at post-mortem compared to 11.8% of those that were SICTT +ve (standard reactor)/IFN-γ −ve. These results highlight the risk associated with retaining SICTT −ve/IFN-γ +ve animals, and suggest that prompt removal of these animals is necessary to reduce the potential for future transmission.

Incorporating indicators for pig health and welfare at meat inspection could reduce the need for on-farm assessments. Skin and tail lesions are important welfare indicators in pigs with good potential to record during meat inspection and could possibly function as iceberg indicators of on farm welfare. The aim of this study was to validate the use of these carcass lesions at meat inspection for the assessment of pig health and welfare on farm. Thirty-one farrow-to-finish pig farms (∼12% of Irish herds) were assessed using an adapted version of the Welfare Quality protocol by inspecting 6 randomly selected pens of pigs in the first weaner (4 to 8 wk), second weaner (8 to 13 wk) and finisher stage (13 to 23 wk). The average prevalence of welfare outcomes for each stage was calculated. One batch of pigs was observed at slaughter and skin and tail lesions were scored according to severity for each carcass. The average prevalence of carcass lesion outcomes was calculated for each farm. Linear regression models were developed to predict the prevalence of each welfare outcome in each stage based on the prevalence of the different carcass lesions. The welfare outcomes of different welfare aspects that were best predicted by abattoir information (highest ) were poor body condition (first weaner stage), bursitis (second weaner stage), huddling (first weaner stage), severe tail lesions (finisher stage) and coughing (second weaner stage). Regression trees and receiver-operating curves (ROC) were used to evaluate the usefulness of carcass lesions as monitoring tools. Receiver-operating curves were created using the 75th percentile to classify farms as a problem farm for these welfare outcomes. Cut-off values of predictive carcass lesion prevalence were similar using both techniques. Models for predicting problem farms with poor body condition, bursitis and severe tail lesions were moderately accurate. Sensitivity and specificity ranged from 75 to 100% and 70 to 87%, respectively at the optimal cut-off value of the predictive carcass lesion prevalence. Results show potential for using carcass skin and tail lesions as iceberg indicators of pig health and welfare on farm. Future work is needed to evaluate the cost of including carcass lesion recording at meat inspection, the cost of failing to identify problem farms and the cost of incorrectly visiting or penalizing problem farms before carcass lesions can be used as welfare indicators in a commercial setting.

Background Acquired β-lactamases are not a common β-lactam resistance mechanism in E. cloacae. In this species, porin mutations decreasing β-lactams permeability are associated with overexpression of the constitutive AmpC with or without increased efflux contributing to β-lactam resistance. We subjected 6 E. cloacae isolates to 10-day serial passage with cefepime (FEP), meropenem (MER), and ceftazidime-avibactam (CAZ-AVI) to evaluate resistance level and mechanism in the mutant strains. Methods Serial passaging was performed in broth microdilution (BMD). Isolated colonies growing in the highest antimicrobial concentrations were submitted to short-read whole genome sequencing (WGS) and analyzed for β-lactam resistance mechanisms. Final mutants displaying > 2-fold changes from the baseline and baseline isolates were sequenced using long-read WGS for single nucleotide polymorphism (SNP) analysis. Results After 10-day passaging, 3 (50.0%) isolates displayed FEP resistance, but only 1 (15.0%) displayed resistance to MER or CAZ-AVI (Table). MIC changes were 4 to 64-fold for FEP, 16 to 64-fold for MER and 2 to 32-fold for CAZ-AVI. SNP analysis demonstrated that final resistant mutants had diverse mechanisms. MER and CAZ-AVI selected for AmpC mutants E61V, G213D, and V303E. OmpC and AcrA regulator alterations were noted in MER and CAZ-AVI mutants for 1 isolate. Mutations in the ABC transporter UrtB and the cell division inhibitor MioC were observed when 1 isolate was exposed to any of the 3 agents. Mutants for 1 isolate had deletion of OmpC (PCR confirmed). Mutations in the upstream region of various genes and gene regulators were observed. The highest CAZ-AVI MIC values were noted in an isolate displaying a mutation in an RND transported permease. Table Conclusion FEP displayed more resistant mutants when compared to MER and CAZ-AVI. Despite the low MIC values of the mutant isolates for MER, the fold changes for this agent were higher than in FEP and CAZ-AVI. Resistance mechanisms in the mutants were complex. Only a few isolates had alterations in the genes usually associated with β-lactam resistance in E. cloacae. Further studies should be performed to evaluate if the mutations observed in vitro are present in clinical isolates resistant to these agents. Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jill Lindley, Allergan (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Brieanna Roth, n/a, Allergan (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)

Background Limited therapeutic options are available for the treatment of multidrug resistant (MDR) organisms. Plazomicin (PLZ) is an aminoglycoside developed to overcome common aminoglycoside-resistance mechanisms. We evaluated the activity of PLZ and comparators against Enterobacterales isolates collected in 2018-2019 carrying genes encoding ESBLs, carbapenemases, and AMEs. Methods Among 3,899 Enterobacterales isolates from US hospitals susceptibility (S) tested using reference broth microdilution method, 619 isolates from selected species displaying elevated MIC values for cephalosporins, carbapenems and/or resistance (CLSI criteria) to amikacin (AMK), gentamicin (GEN) and tobramycin (TOB) were submitted to whole genome sequencing for detection of resistance genes. Results Most isolates producing ESBLs (n= 418) carried blaCTX-M (n= 386). The activity of PLZ (99.3% susceptible [S]) was comparable to that of colistin and higher than other comparators against ESBL isolates (Figure). AMK inhibited 96.4% of the isolates and GEN and TOB inhibited 57.9% and 43.5%, respectively. Only 34 isolates produced carbapenemases, including 19 KPC-2, 10 KPC-3, 1 each with VIM-1, OXA-181, NDM-5 and KPC-2-like plus 1 isolate carrying the genes encoding NDM-1 and OXA-232. These isolates displayed higher resistance rates to comparators and only PLZ, and tigecycline inhibited >90% of these isolates. AMK and GEN inhibited 67.6% and 55.9% of these isolates, respectively. PLZ was active against 97.7% of isolates carrying AME genes (n= 306) that carried aac(6’)-Ib-cr (n =177), aac(3)-IIa (n = 159) and aac(3)-IId (n =81), among others. Most of these isolates were resistant to GEN and TOB (only 10.8-14.1% S), but 92.8% were S to AMK. Three K. pneumoniae isolates carried 16S rRNA methyltransferases, 1 armA (also harboring NDM-1) and 2 rmtB1. Conclusion The activity of PLZ against Enterobacteriaceae isolates carrying AMEs, ESBLs, and carbapenemases was greater than the activity of other aminoglycosides tested and comparable to those of tigecycline and colistin against carbapenemase-producing organisms. Isolates carrying genes encoding ESBLs, AMEs and carbapenemases are usually MDR and PLZ had activity against these organisms collected in the US. Figure 1 Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Valerie Kantro, n/a, Cipla Ltd. (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Jaideep Gogtay, n/a, Cipla Ltd. (Employee) Sandhya Das, n/a, Cipla Ltd. (Research Grant or Support)

Background ST258 K. pneumoniae and ST131 E. coli clones are considered vectors for the global spread of multidrug resistance. We evaluated the activity of β-lactams in combination with QPX7728, a novel β-lactamase inhibitor active against all β-lactamase classes, against a collection of 210 isolates belonging to these clones collected from a worldwide surveillance study. Methods A total of 118 ST258 K. pneumoniae and 92 ST131 E. coli (single loci variant also included) were susceptibility tested by reference broth microdilution against various β-lactams ± QPX7728 and comparator agents. All isolates were screened for β-lactamases using whole genome sequencing analysis. Results All β-lactam agents had limited activity against 118 ST258 K. pneumoniae (1.7–7.6% susceptible). Among these, 104 carried carbapenemase-encoding genes: 66 KPC variants, 20 NDM and 17 OXA-48-like. One isolate carried 2 carbapenemases. The addition of QPX7728 at 4 mg/L or 8 mg/L lowered the MICs for cefepime (MIC50/90, 0.25/1 mg/L and MIC50/90, 0.12/0.5 mg/L), ceftolozane (MIC50/90, 0.5/ > 32 mg/L and MIC50/90, 0.25/16 mg/L), ertapenem (MIC50/90, 0.12/2 mg/L and MIC50/90, 0.06/0.5 mg/L), and meropenem (MIC50/90, 0.06/0.5 mg/L and MIC50/90, 0.03/0.12 mg/L; Table). QPX7728 at 4 mg/L reduced the ceftibuten (MIC50/90, 0.25/8 mg/L) or tebipenem (MIC50/90, 0.12/2 mg/L) MICs for ST258 isolates. E. coli ST131 carried mainly CTX-M variant (85 isolates), but 6 isolates harbored carbapenemases. Carbapenems were the only β-lactams displaying > 80.0% activity against ST131 E. coli, followed by piperacillin-tazobactam (79.3% susceptible). Only 5.4%and 41.3% ST131 isolates were susceptible to cefepime and ceftibuten, respectively. MIC50/MIC90 values for these agents with QPX7728 were ≤ 0.015/≤ 0.015 mg/L for cefepime and ≤ 0.015/0.06 mg/L for ceftolozane with the inhibitor at 8 mg/L and ≤ 0.015/0.03 mg/L for ceftibuten with the inhibitor at 4 mg/L. Conclusion QPX7728 lowered the MICs for all agents tested to clinically achievable levels when tested against isolates multidrug resistant belonging to important clones responsible to the dissemination of KPC, CTX variants, and metallo-β-lactamases. The development of this broad β-lactamase inhibitor should be pursued. Table 1 Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Jill Lindley, Allergan (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Olga Lomovskaya, PhD, Qpex Biopharma (Employee)

Background In general surgery residency, hepatobiliary training varies significantly across the world. The aim of this study was to establish an international consensus among hepatobiliary surgeons on components of a hepatobiliary curriculum for general surgery residents. Methods A three-round modified Delphi technique was employed. Fifty-two hepatobiliary surgeons involved in general surgery training programs were invited. An initial questionnaire was developed by a group of experts in hepatobiliary and educational research after a systematic literature review. It comprised 90 statements about knowledge, technical skills, attitudes, and postoperative care. Panelists could add or alter items. The survey was delivered electronically and the panel was instructed to score the items based on 5-point Likert scale. Consensus was reached when at least 80% of panelists agreed on a statement with Cronbach's alpha value >0.8. Results Forty-one (79%) experts have participated. Sixteen panelists are based in Asia, 14 in Europe, and 11 in the Americas. Eighty percent of all proposed skills (81/101) were considered fundamental including knowledge (39/43), technical skills (16/32), attitude (15/15), and postoperative care (11/11). Conclusion An international consensus was achieved on components of a hepatobiliary curriculum. Acquiring broad knowledge is fundamental during residency. Advanced liver resection techniques require specialized hepatobiliary training.

Introduction: There is interest in new therapies for severe asthma, and how network clinics can facilitate this. Aims and Objectives: We aimed to: 1) explore comorbidities and adherence issues in children referred to our regional multidisciplinary (MDT) asthma clinic 2) describe the interventions utilised by the specialist medical, psychology, nursing, pharmacy, and physiotherapy teams. Method: Retrospective casenote review of referrals into the clinic since July 2018. We extracted data on demographics, co-morbidities, and issues with inhaler technique and adherence. We summarised medical and non-medical interventions used in the clinic. Results: 52 patients were referred (Median age 13 years [IQR 10-15], 37/52 male; 17/52 (32%) demonstrated persistently low FEV1, and 29/52 (55%) had persistently high FeNO. 45/52 (86%) had suboptimal inhaler technique and/or adherence issues. 31/52 (60%) had concurrent medical issues such as allergy, obesity and adrenal insufficiency. 44/52 (85%) had dysfunctional breathing or low fitness on formal step testing. 40/52 (77%) had psychological comorbidities such as anxiety, depression, and low self-esteem. We changed inhalers in 14 patients and utilised methylprednisolone in 1 patient. Due to these interventions we have not needed to start any patient on biologic therapies, immunomodulators or maintenance oral steroids for asthma, and we successfully stopped these in 4 patients. Conclusion: Inhaler competency and adherence, breathing technique, fitness, and psychological problems are common in children with poor asthma control. Addressing these fundamental issues using an MDT specialist clinic can usually negate the need to step up medical treatment, even in children with severe asthma.

Introduction Direct-acting antivirals (DAA's) have revolutionized hepatitis-C virus (HCV) treatment, however controversy remains regarding timing of treatment in relation to liver-transplant (LT). Methods Single-center retrospective study assessing outcomes of listed HCV positive patients in the DAA-era (2014–2017). Patients treated with DAA's before LT (DAA pre-LT) were compared to those who were not treated before LT (No DAA pre-LT) Results 156 HCV positive patients were listed during study-period; 104 (67%) underwent LT while 52 (33%) were de-listed. Of transplanted patients, 48 (46%) received DAA pre-LT while 56 (54%) were treated post-LT. Both groups were comparable in age, gender, MELD, patient and graft survival and cure-rates (98% in DAA pre-LTvs.95% in No DAA pre-LT; p > 0.05). DAA pre-LT group required higher number of treatments-per-patient to clear virus (1.46vs.1.06; p = 0.0006), spent more time on waitlist (331d.vs150d; p = 0.0040) and were less likely to receive livers from HCV positive donors (6%vs.25%; p = 0.0148). Twenty-nine (56%) of the 52 delisted received DAA. They had lower listing-MELD (12vs.18; p = 0.0033), and were more likely to be delisted for “condition improved” (34%vs.4%; p = 0.0143) compared to the 23 (44%) delisted patients who did not receive DAA's. Conclusions DAA's were equally effective in clearing HCV in listed patients irrespective of timing. DAA pre-LT can disadvantage some patients through increase number of treatments needed and longer waitlist times, but treatment in some listed patients with low-MELD can improve condition and alleviate need for LT.

During qualification thermal testing of the Transiting Exoplanet Survey Satellite (TESS) lens assemblies, an anomalous focus change was observed during thermal-vacuum testing at its cold operating temperature (-75°C to - 85°C). Optical testing of the lens assemblies performed in the thermal-vacuum chamber indicated the magnitude and direction of the focus change, but did not identify the specific changes in the lens elements that were causing the focus shift. Individual lens motions measured using an interferometer indicated that lens vertices were moving relative to one another in a way that was inconsistent with predictions from detailed structural/thermal/optical (STOP) modeling. Further STOP analysis indicated the focus and vertex motion data were consistent with changes in lens curvature, suggesting that radial forces were deforming the lens. Finite element modeling showed that material property changes in the silicone adhesive material (room temperature vulcanizing, RTV 566) used to bond the lenses to the aluminum bezels could produce the necessary forces. The root cause of the focus shift was suspected to be unanticipated crystallization of the RTV 566 which has not previously been documented. Despite its widespread use, very little information has been published about the mechanical properties of RTV 566, and typical thermomechanical testing of its behavior has always utilized temperature sweeps. For this investigation, extensive testing was performed to characterize material property changes of RTV 566 samples under isothermal conditions at low temperatures (-75 to -85°C), for extended periods and at different levels of applied strain. The data presented here provide conclusive evidence that RTV 566 experiences time-dependent changes in mechanical properties that are consistent with crystallization phenomena.

Aims: The purpose of this study was to assess Emirati university students’ knowledge of physical activity guidelines and perceptions of the benefits of physical activity for mental health. Methods: A random sample ( n = 628) completed an online questionnaire assessing the recommended amount of physical activity for good health (min/week) and to what extent exercise can help improve wellbeing, and manage depression and anxiety/stress (5-point Likert-type scale). Results: Only 3% of respondents identified 150 min/week and less than half (39%) of the respondents reported an amount within the range of 150–300 min/week. Most respondents believed that physical activity could improve wellbeing (69%), and manage depression (71%) and anxiety/stress (74%). Females were more likely than males to view physical activity as a way to manage depression ( p = .003), and anxiety/stress ( p = .002). Conclusions: More work may be required to promote awareness of physical activity guidelines in this population, and males’ awareness of mental health benefits of physical activity.

Background Aztreonam (ATM) is a monobactam stable to hydrolysis by metallo-β-lactamases (MBL). Avibactam (AVI) is a non-β-lactam β-lactamase inhibitor that inhibits serine carbapenemases (CPEs), such as ESBLs, KPCs, AmpC, and some OXAs. ATM-AVI is under clinical development for treatment of serious infections caused by Gram-negative bacteria (GNB), including MBL-producers. Methods 2,582 GNB (1,630 Enterobacterales [ENT] and 952 nonfermentative-GNB) were consecutively collected (1/patient) from 56 medical centers located in Western Europe (W-EU; 22 centers in 10 nations), Eastern Europe (E-EU; 12 centers in 9 nations), Latin America (LATAM; 10 centers 6 nations), and the Asia-Pacific region (APAC; 12 centers in 8 nations) in 2019 and susceptibility (S) tested against ATM-AVI and comparators at a central laboratory by reference broth microdilution methods. Results Overall, 99.9% of ENT (MIC50/90, 0.06/0.25 mg/L), including 99.1% of carbapenem-resistant ENT (CRE; MIC50/90, 0.25/0.5 mg/L), were inhibited at an ATM-AVI MIC of ≤ 8 mg/L (Table). CRE rates were 1.4%, 23.7%, 6.3%, and 9.6% in W-EU, E-EU, LATAM, and APAC, respectively (6.9% overall). A CPE was identified in 95 of 113 CRE isolates (84.1%). These CPEs included NDM-like (31.0% of CRE), KPC-like (26.5%), OXA-48-like (24.8%), and VIM-like (7.1%). Six isolates produced 2 CPEs. The highest ATM-AVI MIC value among MBL-producers (n=43; MIC50/90, 0.12/0.5 mg/L) was 4 mg/L. Among P. aeruginosa, 75.1% were inhibited at ≤ 8 mg/L of ATM-AVI; S to meropenem (MEM), piperacillin-tazobactam, and ceftazidime were 69.4%, 72.5%, and 75.7%, respectively, and ranged from 64.3% in E-EU to 82.0% in W-EU. MEM non-S P. aeruginosa varied from 22.2% in W-EU to 54.8% in E-EU. ATM-AVI was highly active against S. maltophilia, inhibiting 95.0%, 100.0%, 100.0%, and 90.0% of isolates from W-EU, E-EU, LATAM, and APAC, respectively, at ≤8 mg/L. S. maltophilia S to cotrimoxazole were 90.0%, 97.7%, 85.7%, and 100.0% in W-EU, E-EU, LATAM, and APAC, respectively. ATM-AVI also was very active against Burkholderia spp. (highest MIC, 8 mg/L). Conclusion Our results support clinical development of ATM-AVI to treat pneumonia caused by ENT (including MBL-producers), P. aeruginosa, S. maltophilia, and Burkholderia spp. Table 1 Disclosures Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support) Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cecilia G. Carvalhaes, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Pfizer (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support)

Background Most CRE isolates in US hospitals produce KPC enzymes, but some do not carry carbapenemases. We investigated the prevalence, resistance mechanisms and activity of ceftazidime-avibactam and comparator agents against CRE that did not carry carbapenemase genes from US hospitals. Additionally, meropenem-resistant isolates were tested for meropenem-vaborbactam. Methods A total of 28,904 Enterobacterales isolates were collected in 70 US hospitals during 2016-2018, and susceptibility tested by reference broth microdilution. Meropenem-vaborbactam was tested using lyophilized panels following the manufacturer’s instructions. CRE isolates were submitted to whole genome sequencing for the screening of b-lactamase genes, multilocus sequence typing, changes in outer membrane protein (OMP) genes and AmpC expression levels. Results A total of 304 (1.1%) CREs were observed in the study period and 45 (14.8%) isolates did not carry carbapenemases. These isolates were mainly Klebsiella aerogenes, Enterobacter cloacae and Klebsiella pneumoniae (11, 11 and 10 isolates, respectively), but also included 5 other species. Acquired b-lactamase genes were detected among 17 isolates and blaCTX-M-15 was the most common (13 isolates). All K. aerogenes and 10 E. cloacae did not carry acquired b-lactamase genes. Ceftazidime-avibactam (100% susceptible) inhibited all isolates at the current breakpoint, followed by tigecycline and amikacin (> 80% susceptible). Other comparators were not active against non-carbapenemase-producing CRE. Nine of 35 meropenem-resistant isolates displayed meropenem-vaborbactam MIC values of ≥ 8 mg/L (nonsusceptible). Further analysis showed that 23 isolates had disruption of OmpC/OmpK36, 4 had disrupted OmpF/OmpK35 and 13 had both OMP genes disrupted. Additionally, 7 isolates had elevated AmpC expression among 17 isolates tested. Among 7 E. coli, 4 were ST131 and only 2 of 10 K. pneumoniae were clonal complex 11. Conclusion Therapy options for treatment of infections caused by CRE were very limited until recent approval of new agents with activity against these isolates. Ceftazidime-avibactam demonstrated full in vitro activity against all carbapenemase-negative CRE carrying multiple resistance mechanisms. Disclosures Mariana Castanheira, PhD, 1928 Diagnostics (Research Grant or Support)A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Amplyx Pharmaceuticals (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cidara Therapeutics (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Fox Chase Chemical Diversity Center (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Merck & Co, Inc. (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Timothy B. Doyle, Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Pfizer (Research Grant or Support)Qpex Biopharma (Research Grant or Support) Cory Hubler, Allergan (Research Grant or Support) Rodrigo E. Mendes, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Basilea Pharmaceutica International, Ltd (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Department of Health and Human Services (Research Grant or Support)GlaxoSmithKline (Research Grant or Support)Melinta Therapeutics, Inc. (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Pfizer (Research Grant or Support) Helio S. Sader, MD, PhD, A. Menarini Industrie Farmaceutiche Riunite S.R.L. (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Allergan (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Cipla Ltd. (Research Grant or Support)Melinta (Research Grant or Support)Merck (Research Grant or Support)Merck (Research Grant or Support)Paratek Pharma, LLC (Research Grant or Support)Pfizer (Research Grant or Support)

PURPOSE: To identify peri-operative risk factors and time to onset of pancreatic endocrine/exocrine insufficiency. METHODS: We retrospectively analyzed a single institutional series of patients who underwent pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) between 2000 and 2015. Endocrine/exocrine insufficiencies were defined as need for new pharmacologic intervention. Cox proportional modeling was used to identify peri-operative variables to determine their impact on post-operative pancreatic insufficiency. RESULTS: 1,717 patient records were analyzed (75.47% PD, 24.53% DP) at median follow-up 17.88 months. Average age was 62.62 years, 51.78% were male, and surgery was for malignancy in 74.35% of patients. Post-operative endocrine insufficiency was present in 20.15% (n=346). Male gender (p= 0.015), increased body mass index (BMI) (p

Purpose The care of the patient with cystic fibrosis (CF) requires a multidisciplinary approach throughout the lifespan by teams specially trained to deal with the complexities of care. Improvements in therapies have resulted in increased life expectancy of those with CF, yet respiratory failure continues to be the leading cause of death. While lung transplant (LTx) can be a viable treatment option, 35% of CF patients who meet criteria are not referred. We sought to understand patient preferences regarding discussions surrounding LTx in anticipation of referral to the LTx center. Methods A cross-sectional survey was developed to understand the patient's perspective on LTx transition. The survey was sent, via MyChart, to a retrospective cohort of CF patients who were seen as a new patient in the LTx center over a two-year period, and we provided the survey at the end of initial LTx clinic encounter. Results Patients representing eight CF centers participated. All respondents identified the CF pulmonologist as discussing LTx (N=17). 52% of patients also discussed Ltx with another member of the CF team (Figure 1). Conversely 88% of respondents wanted to hear about LTx from members of the team other than their physician. In fact 35% of respondents did not select the pulmonologist as someone they felt comfortable speaking to regarding LTx. Conclusion Due to the success of the multidisciplinary approach in CF clinics, patients often prefer to discuss treatment options with a variety of clinicians. The decision to refer to LTx can be overwhelming for the patient and the CF team, who may lack comfort in discussing LTx. The responses reflecting multiple CF programs suggests this problem is not center-specific, but relevant across CF centers

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5-15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.

Background The pancreas is a rare site of metastases, although metastatic renal cell carcinoma (mRCC) is the most commonly reported secondary tumor. Pancreatectomy has been described in selected patients with localized metastases, but long-term benefit remains poorly defined. Methods A retrospective review of a prospectively maintained database was performed to evaluate the outcomes of patients undergoing pancreatectomy for mRCC at a tertiary care center from 1995–2017. Postoperative complications were evaluated using the Modified Accordion Grading System (MAGS) and Kaplan–Meier curves and log-rank tests were utilized for survival analysis. Results 29 patients underwent pancreatectomy for mRCC including 15 distal pancreatectomies (DP), 10 pancreaticoduodenectomies (PD) and 4 total-pancreatectomies (TP). The mean age was 67 ± 8 years, and 15 were male. The median time from index nephrectomy to pancreatectomy was 8 (IQR: 3.72–12.2) years. There was no 90 Day post-pancreatectomy mortalities and the morbidity incidence included 13 Minor MAGS and 8 Severe MAGS complications respectively. Post-pancreatectomy disease specific survival at 2- and 4-years were 89% and 80% with 12 patients being alive at last follow up. Conclusions Pancreatic resection can be safely performed in select patients with localized mRCC with favorable long-term outcomes.

Abdominal organ transplantation faces several challenges: burnout, limited pipeline of future surgeons, changes in liver allocation potentially impacting organ procurement travel, and travel safety. The organ procurement center (OPC) model may be one way to mitigate these issues. Liver transplants from 2009 to 2016 were reviewed. There were 755 liver transplants performed with 525 OPC and 230 in-hospital procurements. The majority of transplants (87.4%) were started during daytime hours (5 am-7 pm). Transplants with any portion occurring after-hours were more likely to have procurements in-hospital (P < .001). Daytime cases (n = 400) had more OPC procured livers and hepatitis C recipients and were less likely to have a donation after circulatory death donor (all P < .05). In adjusted analyses, daytime cases were independently associated with extubation in the operating room and less postoperative transfusion. There were no significant differences in short- or long-term postoperative outcomes. For exported livers, 54.3% were procured by a local team, saving 137 flights (151 559 miles). The OPC resulted in optimally timed liver transplants and decreased resource utilization with no negative impact on patient outcomes. It allows for ease in exporting organs procured by local surgeons, and potentially addresses provider burnout, the transplant surgery pipeline, and surgeon travel.

Will there be a breakthrough in the field of information retrieval. One authority in that field has said, ''No.'' This paper adopts the opposite viewpoint, and speculates on what the elements of such a breakthrough might be if it were to occur. Several breakthroughs in other fields are scrutinized in order to highlight the factors which characterize and energize sudden expansions of new technologies. These factors, plus some factors specific to the field of information retrieval, are then extrapolated into a ''plot for a breakthrough.''

Background Ceftazidime–avibactam (CAZ-AVI) and ceftolozane-tazobactam (C-T) display excellent antipseudomonal activity, but Pseudomonas aeruginosa (PSA) susceptibility against these agents can be affected by acquired resistance genes and mutations. We evaluated resistance mechanisms against these agents among 109 PSA isolates using WGS and messenger (m)RNA-sequencing. Methods PSA clinical isolates from Europe (n = 62), Asia-Pacific (n = 22), and Latin America (n = 25) in 2017 were susceptibility tested using reference methods and 109 were randomly selected for WGS and total mRNA-sequencing. Data were analyzed using custom software and logistic regression. Results Isolates carrying metallo-β-lactamases (MBLs) (n = 24) were resistant to all β-lactams, including CAZ-AVI and C-T. The only compound inhibiting >50% of the isolates was colistin. ESBL genes (blaVEB-1 or blaVEB-9), some oxacillinases, and PDC variants caused resistance to CAZ-AVI and C-T, but the presence of blaPER-1, blaGES-6, and PDC-97 led to resistance to C-T, but not to CAZ-AVI. Disruptions of ampR (PDC regulator) and glnD (nitrogen metabolism) were associated with resistance to CAZ-AVI and C-T, but armZ (anti-repressor of mexZ) disruption was only associated with C-T resistance. The combination of wild-type sequences of various genes was negatively associated with resistance to CAZ-AVI and C-T, but alterations in dnaJ (chaperone) and oprM were only related to C-T resistance. mRNA-sequencing data did not show strong correlations with CAZ-AVI or C-T resistance or with expression of genes involved in β-lactam resistance, but further analyses will expand the genes analyzed. Interestingly, among 14 isolates overexpressing MexAB-OprM that extrude CAZ, only 6 had CAZ-AVI MICs >8 mg/L. Conclusion Resistance mechanisms against CAZ-AVI and C-T remain poorly understood beyond MBL acquisition. In this study, resistance mechanisms statistically associated with CAZ-AVI resistance in PSA were noted among C-T-resistant isolates, but some mechanisms were only observed among C-T-resistant isolates. The richness of results employing these 2 methodologies requires further investigations that are being performed to evaluate sequences and expression alterations. Disclosures All authors: No reported disclosures.