10 years, 100 robotic major hepatectomies: a single-center experience.

INTRODUCTION: Adoption of robotic liver resections has been gradually increasing throughout the HPB surgical community over the past decade. Currently there is limited literature which demonstrates a significant benefit of robotic surgery for major hepatectomies over open or laparoscopic. As one of the first centers to develop a robotic HPB program, we have experienced improved outcomes over time with increasing utilization of robotics. Herein, we present our 10-year experience and outcomes for major robotic liver resections. METHODS: From 2012 to 2022, 361 robotic liver procedures were performed, including 100 major hepatectomies. A retrospective data review of the electronic medical record was performed evaluating outcomes after robotic major hepatectomy. Outcomes for the first 50 cases (Group A) and second 50 cases (Group B) were compared to identify any improvements in practice. Demographic and clinical outcome variables were analyzed. Data were assessed for normality, and Wilcoxon rank-sum, χ2 tests, and a logistic regression model were performed appropriate for the data. Stata v.17 was utilized, and significance was set as p < .05. RESULTS: There was no difference in median operative time (258 vs 256 min), EBL (500 vs 500 mL), median LOS (5 vs 3.5 days), 90-day readmission (14% vs 24%), major complications (14% vs 20%), and 90-day mortality (6% vs 4%) between early and late cases, respectively. ICU admissions and conversion rates were significantly lower in group B (14.0% vs 48.0%), while expert level difficulty indices were higher (82% vs 58%). CONCLUSION: Development of a robotic liver program with good outcomes is feasible over time. Our data suggest that our institutional learning curve for robotic major hepatectomy plateaued at approximately 50 cases.

Enhanced Recovery after Surgery recommendations that most impact patient care: A multi-institutional, multidiscipline analysis in the United States.

BACKGROUND: Compliance to the entire Enhanced Recovery after Surgery (ERAS) protocol improves surgical recovery, where higher compliance improves outcomes. However, specific items may predict improved recovery more than others. Studies have evaluated the impact of individual ERAS recommendations though they are either single center, not based in the United States (US), or focus on colorectal procedures only. This study aims to evaluate compliance on surgical outcomes in two large healthcare systems in the US across four surgery types. METHODS: Compliance to individual recommendations, limited patient characteristics, and outcomes data from two US ERAS Centers of Excellence (CoE) for hepatectomy, pancreatectomy, radical cystectomy, and head and neck (HN) resections were evaluated. Outcomes included 30-day Clavien-Dindo≥3, readmission, mortality, and length of stay (LOS). Multivariate regressions were performed as appropriate for the data for each surgery type. Clavien≥3 was included to control for severity of complications, and the CoE variable was force-retained. RESULTS: A total of 2886 records were analyzed. Controlling for CoE and severity of patient complications, early removal of Foley catheter was associated with significant reductions in LOS in the liver, pancreas, and HN procedures and reductions in complications in the liver and pancreas. Limited use of NG tubes reduced LOS in the pancreas and complications in urology. Oral carbohydrate loading reduced LOS in the pancreas, and patient education reduced mortality in HN patients. CONCLUSIONS: This study reports the effect of ERAS compliance on outcomes, by surgery type, in a multi-institutional US setting. Future studies should validate these findings and consider surgery-specific predictive models comprised of individual ERAS recommendations in real-world applications.

COVID-19 and the Impact on Delirium Care of Hospitalized Older Adults: A Qualitative Study.

BACKGROUND: Older adult patients with COVID-19 and delirium experience higher rates of adverse outcomes. Early recognition of at-risk patients and implementation of management strategies improve outcomes, though understanding barriers to acute care nurses implementing these strategies is limited. PURPOSE: This study's purpose was to understand the experiences of acute care nurses providing care to older adults with COVID-19 and delirium. Experiences explored included assessment, nursing management interventions, and barriers to care. METHODS: Purposive sampling to recruit nurses for semistructured focus groups was performed, and thematic analysis was generated by 4 members of the research team. RESULTS: Twenty-one nurses participated in focus groups. Thematic analysis revealed themes of increased patient social isolation, barriers to delirium assessment and prevention, increased staff demands, and stressful work environments. CONCLUSION: Rich findings reveal the profound impact of the pandemic on assessment for delirium and implementation of strategies for prevention and management in older adult patients.

Impact of Multidisciplinary Audit of Enhanced Recovery After Surgery (ERAS)® Programs at a Single Institution.

BACKGROUND: As Enhanced Recovery After Surgery (ERAS®) programs expand across numerous subspecialties, growth and sustainability on a system level becomes increasingly important and may benefit from reporting multidisciplinary and financial data. However, the literature on multidisciplinary outcome analysis in ERAS is sparse. This study aims to demonstrate the impact of multidisciplinary ERAS auditing in a hospital system. Additionally, we describe developing a financial metric for use in gaining support for system-wide ERAS adoption and sustainability. METHODS: Data from HPB, colorectal and urology ERAS programs at a single institution were analyzed from a prospective ERAS Interactive Audit System (EIAS) database from September 2015 to June 2019. Clinical 30-day outcomes for the ERAS cohort (n = 1374) were compared to the EIAS pre-ERAS control (n = 311). Association between improved ERAS compliance and improved outcomes were also assessed for the ERAS cohort. The potential multidisciplinary financial impact was estimated from hospital bed charges. RESULTS: Multidisciplinary auditing demonstrated a significant reduction in postoperative length of stay (LOS) (1.5 days, p < 0.001) for ERAS patients in aggregate and improved ERAS compliance was associated with reduced LOS (coefficient - 0.04, p = 0.004). Improved ERAS compliance in aggregate also significantly associated with improved 30-day survival (odds ratio 1.04, p = 0.001). Multidisciplinary analysis also demonstrated a potential financial impact of 44% savings (p < 0.001) by reducing hospital bed charges across all specialties. CONCLUSIONS: Multidisciplinary auditing of ERAS programs may improve ERAS program support and expansion. Analysis across subspecialties demonstrated associations between improved ERAS compliance and postoperative LOS as well as 30-day survival, and further suggested a substantial combined financial impact.

A 2-Year Experience With Enhanced Recovery After Surgery: Evaluation of Compliance and Outcomes in Pancreatic Surgery.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) programs reduce recovery time, length of stay (LOS), and complications after major surgical procedures. PURPOSE: We evaluated our 2-year experience with a newly implemented comprehensive ERAS program at a high-volume center after pancreatic surgery. METHODS: Outcomes, cost, and compliance metrics were assessed in 215 patients who underwent elective pancreatic surgery (pre-ERAS; n = 99; post-ERAS: n = 116). Mann-Whitney U and χ2 tests were used to evaluate continuous and categorical variables. RESULTS: There were significant decreases in LOS and cost in the post-ERAS cohorts. There were significant increases in compliance with ERAS implementation. Postoperative complication, readmission, and survival rates did not increase. CONCLUSIONS: Implementation of ERAS at a large-volume hospital may improve compliance and reduce costs and LOS without increasing adverse outcomes.

The next step in surgical quality improvement: outcome situational awareness

Summary: A similar theme unites proposed solutions for stagnant improvement in outcomes and rising health care costs: eliminate unnecessary variation in the care of surgical patients. While large quality-improvement projects like the Americal College of Surgeons National Surgical Quality Improvement Program have historically led to improved patient outcomes at the hospital level, the next step in surgical quality improvement is to eliminate unnecessary variation at the level of the individual surgeon. Critical examination of individualized clinical, financial and patient-reported outcomes ­ outcome situational awareness ­ along with peer group comparison will help surgeons to identify variation in patient care. We are piloting an interactive software platform at our institution to provide information on individualized clinical, financial and patient-reported outcomes in real time through automatic data population of a central REDCap database. These individualized data along with peer group comparison allow surgeons to objectively determine areas of potential improvement.

Robotic-assisted versus laparoscopic left pancreatectomy at a high-volume, minimally invasive center.

INTRODUCTION: While minimally invasive left pancreatectomy has become more widespread and generally accepted over the last decade, opinions on modality of minimally invasive approach (robotic or laparoscopic) remain mixed with few institutions performing a significant portion of both operative approaches simultaneously. METHODS: 247 minimally invasive left pancreatectomies were retrospectively identified in a prospectively maintained institutional REDCap™ database, 135 laparoscopic left pancreatectomy (LLP) and 108 robotic-assisted left pancreatectomy (RLP). Demographics, intraoperative variables, postoperative outcomes, and OR costs were compared between LLP and RLP with an additional subgroup analysis for procedures performed specifically for pancreatic adenocarcinoma (35 LLP and 23 RLP) focusing on pathologic outcomes and 2-year actuarial survival. RESULTS: There were no significant differences in preoperative demographics or indications between LLP and RLP with 34% performed for chronic pancreatitis and 23% performed for pancreatic adenocarcinoma. While laparoscopic cases were faster (p < 0.001) robotic cases had a higher rate of splenic preservation (p < 0.001). Median length of stay was 5 days for RLP and LLP, and rate of clinically significant grade B/C pancreatic fistula was approximately 20% for both groups. Conversion rates to laparotomy were 4.3% and 1.8% for LLP and RLP approaches respectively. RLP had a higher rate of readmission (p = 0.035). Pathologic outcomes and 2-year actuarial survival were similar between LLP and RLP. LLP on average saved $206.67 in OR costs over RLP. CONCLUSIONS: This study demonstrates that at a high-volume center with significant minimally invasive experience, both LLP and RLP can be equally effective when used at the discretion of the operating surgeon. We view the laparoscopic and robotic platforms as tools for the modern surgeon, and at our institution, given the technical success of both operative approaches, we will continue to encourage our surgeons to approach a difficult operation with their tool of choice.

Robotic-assisted versus laparoscopic major liver resection: analysis of outcomes from a single center.

BACKGROUND: Debate exists regarding outcomes of robot-assisted versus laparoscopic hepatectomy. We reviewed and analyzed major hepatectomies (resection of ≥3 Couinaud liver segments) performed in a minimally invasive fashion at a single institution. METHODS: From 2011 to 2016, 473 major hepatectomy procedures were performed, of which 173 (37%) were performed in a minimally invasive fashion (57 robot-assisted and 116 laparoscopic). Patient demographics, operating statistics and outcomes were analyzed retrospectively. RESULTS: Patients undergoing robot-assisted versus laparoscopic hepatectomy were older (58.1 vs 53.2 years, respectively; p = 0.030), admitted to ICU postoperatively less frequently (43.9% vs 61.2%, respectively; p = 0.043), and readmitted less often within 90 days (7.0% vs 28.5%, respectively; p = 0.001). No significant differences were identified in relation to complications, blood loss, operative times, and length of stay. CONCLUSION: Robot-assisted is an effective alternative to laparoscopic major hepatectomy for resection of malignant and benign liver lesions. Robotic-assisted offers technical advantages compared to laparoscopic surgery including improved optic visualization, operative dexterity, and ease of dissection and suturing. This experience suggested that the robotic platform was associated with improved outcomes including reduced postoperative ICU admission and 90-day readmission.

Routine versus difficult cholecystectomy: using predictive analytics to assess patient outcomes.

BACKGROUND: The American College of Surgeons National Surgical Quality Improvement Program® (NSQIP) Surgical Risk. Calculator (SRC) estimates postoperative outcomes. The aim of this study was to develop and validate a specific predictive outcomes model for cholecystectomy procedures. METHODS: Patients who underwent cholecystectomy between 2008 and 2016 and were deemed too high risk for acute care general surgery (GS) and had surgery performed by the Division of Hepatopancreatobiliary Surgery (HPB) were identified. Outcomes of the HPB cholecystectomies were matched against cholecystectomies performed by GS. New predictive models for postoperative outcomes were constructed. Area under the curve was used to assess predictive accuracy for both models and internal validation was performed using bootstrap logistic regression. RESULTS: A total of 169/934 (18%) cholecystectomies were identified as too high risk for GS. These 169 patients were matched with 126 patients who had cholecystectomy performed by GS. For GS and HPB cholecystectomies, the proposed model demonstrated better discriminative ability compared to the SRC based on ROC curves (proposed model: 0.589-0.982; SRC: 0.570-0.836) for each of the predicted outcomes. CONCLUSION: For patients undergoing cholecystectomy, customized models are superior for predicting individual perioperative risk and allow more accurate, patient-specific delivery of care.

Implementing Enhanced Recovery After Surgery (ERAS) Program on a Specialty Nursing Unit.

Implementing Enhanced Recovery After Surgery (ERAS) guidelines is an effective method to standardize patient care, improve patient outcomes, and develop quality improvement projects. Completing the required ERAS Implementation Program provided by the International ERAS Society enabled the hepatopancreaticobiliary surgery team at Carolinas HealthCare System to successfully implement evidence-based practice changes for pancreaticoduodenectomy patients on an acuity-adjustable unit resulting in improved care and cost reduction.

Developing and validating a center-specific preoperative prediction calculator for risk of outcomes following major hepatectomy procedures.

BACKGROUND: The American College of Surgeons NSQIP® Surgical Risk Calculator (SRC) was developed to estimate postoperative outcomes. Our goal was to develop and validate an institution-specific risk calculator for patients undergoing major hepatectomy at Carolinas Medical Center (CMC). METHODS: Outcomes generated by the SRC were recorded for 139 major hepatectomies performed at CMC (2008-2016). Novel predictive models for seven postoperative outcomes were constructed and probabilities calculated. Brier score and area under the curve (AUC) were employed to assess accuracy. Internal validation was performed using bootstrap logistic regression. Logistic regression models were constructed using bivariate and multivariate analyses. RESULTS: Brier scores showed no significant difference in the predictive ability of the SRC and CMC model. Significant differences in the discriminative ability of the models were identified at the individual level. Both models closely predicted 30-day mortality (SRC AUC: 0.867; CMC AUC: 0.815). The CMC model was a stronger predictor of individual postoperative risk for six of seven outcomes (SRC AUC: 0.531-0.867; CMC AUC: 0.753-0.970). CONCLUSION: Institution-specific models provide superior outcome predictions of perioperative risk for patients undergoing major hepatectomy. If properly developed and validated, institution-specific models can be used to deliver more accurate, patient-specific care.

Comparing early and delayed repair of common bile duct injury to identify clinical drivers of outcome and morbidity.

BACKGROUND: Outcomes following repair of common bile duct injury (CBDI) are influenced by center and surgeon experience. Determinants of morbidity related to timing of repair are not fully described in this population. METHODS: Patients with CBDI managed surgically at a single center from January 2008 to June 2015 were retrospectively reviewed. Outcomes of patients undergoing early (≤48 h from injury) and delayed (>48 h) repair were compared. Predictive modeling for readmission was performed for patients undergoing delayed repair. RESULTS: In total, 61 patients underwent surgical biliary reconstruction. Between the early and delayed repair groups, no differences were found in patient demographics, injury classification subtype, vasculobiliary injury (VBI) incidence, hospital length of stay, 30-day readmission rate, or 90-day mortality rate. Patients undergoing delayed repair exhibited increased chance of readmission if VBI was present or if multiple endoscopic procedures were performed prior to repair. A predictive model was constructed with these variables (ROC 0.681). CONCLUSION: When managed by a tertiary hepatopancreatobiliary center, equivalent outcomes can be realized for patients undergoing early and delayed repair of CBDI. Establishment of evidence-based consensus guidelines for evaluation and treatment of CBDI may allow identification of factors that drive morbidity and predict clinical outcomes in this population.

Qualities and characteristics of successfully matched North American HPB surgery fellowship candidates.

BACKGROUND: Hepato-pancreato-biliary (HPB) fellowships in North America are difficult to secure with an acceptance rate of 1 in 3 applicants. Desirable characteristics in an HPB surgery applicant have not been previously reported. This study examines the perceptions of trainees and HPB program directors with regards to positive attributes in applicants for HPB fellowships. METHODS: Parallel surveys were distributed by email with a web-link to current and recent HPB fellows in North America (from the past 5 years) with questions addressing the following domains: surgical training, research experience, and mentorship. A similar survey was distributed to HPB fellowship program directors in North America requesting their opinion as to the importance of these characteristics in potential applicants. RESULTS: 32 of 60 of surveyed fellows and 21 of 38 of surveyed program directors responded between November 2014-February 2015. Fellows overall came from fairly diverse backgrounds (13/32 were overseas medical graduates) about one third of respondents having had some prior research experience. Program directors gave priority to the applicant's interview, curriculum vitae, and their recommendation letters (in order of importance). Both the surveyed fellows and program directors felt that the characteristics most important in a successful HPB fellowship candidate include interpersonal skills, perceived operative skills, and perceived fund of knowledge. CONCLUSION: Results of this survey provide useful and practical information for trainees considering applying to an HPB fellowship program.

Training and practice of the next generation HPB surgeon: analysis of the 2014 AHPBA residents' and fellows' symposium survey.

BACKGROUND: Hepato-pancreato-biliary (HPB) surgery is a complex subspecialty drawing from varied training pools, and the need for competency is rapidly growing. However, no board certification process or standardized training metrics in HPB surgery exist in the Americas. This study aims to assess the attitudes of current trainees and HPB surgeons regarding the state of training, surgical practice and the HPB surgical job market in the Americas. STUDY DESIGN: A 20-question survey was distributed to members of Americas Hepato-Pancreato-Biliary Association (AHPBA) with a valid e-mail address who attended the 2014 AHPBA. Descriptive statistics were generated for both the aggregate survey responses and by training category. RESULTS: There were 176 responses with evenly distributed training tracks; surgical oncology (44, 28%), transplant (39, 24.8%) and HPB (38, 24.2%). The remaining tracks were HPB/Complex gastrointestinal (GI) and HPB/minimally invasive surgery (MIS) (29, 16% and 7, 4%). 51.2% of respondents thought a dedicated HPB surgery fellowship would be the best way to train HPB surgeons, and 68.1% felt the optimal training period would be a 2-year clinical fellowship with research opportunities. This corresponded to the 67.5% of the practicing HPB surgeons who said they would prefer to attend an HPB fellowship for 2 years as well. Overall, most respondents indicated their ideal job description was clinical practice with the ability to engage in clinical and/or outcomes research (52.3%). CONCLUSIONS: This survey has demonstrated that HPB surgery has many training routes and practice patterns in the Americas. It highlights the need for specialized HPB surgical training and career education. This survey shows that there are many ways to train in HPB. A 2-year HPB fellowship was felt to be the best way to train to prepare for a clinically active HPB practice with clinical and outcomes research focus.

The impact of an enhanced recovery after surgery protocol for major head and neck oncologic surgery on postoperative complications and adjuvant treatment delivery.

OBJECTIVE: The Commission on Cancer (CoC) recently introduced a quality metric to optimize time between major head and neck surgery and adjuvant treatment (TAT) ≤6 weeks, as TAT delay adversely impacts patient survival. This study evaluates whether enhanced recovery after surgery (ERAS) for this population reduces the rate of postoperative complications, length of stay (LOS), and TAT. METHODS: Patients undergoing larynx or oral cavity resection with free flap reconstruction, ERAS, and adjuvant treatment after 2018 were compared to a historical pre-ERAS cohort. Patients underwent surgery at a single-institution tertiary referral center for complex head and neck oncology. Differences between groups were compared by chi-square, Fisher's exact, or Wilcoxon rank-sum test. TAT >6 weeks was evaluated with univariate and multivariable logistic regression. RESULTS: Thirty-nine pre-ERAS patients were compared to 39 ERAS patients. No demographic differences existed between groups. LOS was improved with ERAS (p = 0.005). ERAS patients were discharged to home and returned to their activities of daily living (ADL) earlier (p = 0.004, 0.001). ADL recovery was associated with on-time TAT ≤42 days on univariate analysis (OR 1.36, 95% CI 1.13-1.63, p = 0.001). TAT delay was less frequent with ERAS (51.3% vs. 69.2%), but this was not significant after multivariable logistic regression (p = 0.11). CONCLUSION: ERAS decreases LOS and returns advanced head and neck cancer patients to their ADL sooner. Postoperative ADL recovery independently predicts on-time adjuvant treatment. Still, compliance beyond 50% with the TAT ≤6 weeks CoC quality metric remains a major treatment barrier.

Impact of nutritional compliance within ERAS protocols for hepatopancreatobiliary, radical cystectomy, and head and neck procedures: A case-matched analysis adjusted for major complications.

BACKGROUND: Enhanced recovery after surgery (ERAS®) pathways aim to improve patient outcomes by applying multimodal practices before, during, and after operative procedures. Compared with standard care before ERAS, we investigated whether compliance to ERAS guidelines for nutritional care, preoperative oral carbohydrate loading and postoperative oral nutrition, was associated with a decrease in hospital length of stay (LOS) after pancreaticoduodenectomy, distal pancreatectomy, hepatectomy, radical cystectomy, and head and neck tumor resection with reconstruction. METHODS: Compliance to ERAS nutrition recommendations was evaluated. Post-ERAS cohort was retrospectively analyzed. Pre-ERAS cohort consisted of case matched patients one year before ERAS: age more than or less than 65 years, body mass index (BMI) more than greater than or less than 30 kg/m2, diabetes mellitus, sex, and procedure. Each cohort consisted of 297 patients. Binary linear regressions evaluated the incremental effect of postoperative nutrition timing and preoperative carbohydrate loading on LOS. Multivariate regressions adjusted for postoperative complications. RESULTS: Compliance with preoperative carbohydrate loading for the post-ERAS cohort was 81.7%. Mean hospital LOS was significantly shorter for the post-ERAS cohort compared with pre-ERAS cohort (8.3 vs 10.0 days, p < 0.001). By procedure, LOS was significantly shorter for patients undergoing pancreaticoduodenectomy (p = 0.003), distal pancreatectomy (p = 0.014), and head and neck procedures (p = 0.024). Early postoperative oral nutrition was associated with a 3.75-day shorter LOS (p < 0.001); no nutrition was associated with a 3.29-day longer LOS (p < 0.001). CONCLUSION: Compliance with ERAS protocols for specific nutritional care practices was associated with a statistically significant decrease in LOS without subsequent increases in 30-day readmission rates and positive financial impact. These findings suggest that ERAS guidelines for perioperative nutrition are a strategic pathway to improved patient recovery and value-based care in surgery.

Enhanced Recovery After Surgery® in Octogenarians Undergoing Hepatopancreatobiliary Surgery.

Advances in perioperative care have increased the frequency of surgical intervention performed on the very elderly (≥80 years). This study aims to investigate the impact of Enhanced Recovery After Surgery (ERAS) on outcomes for octogenarians after major hepatopancreatobiliary (HPB) surgery. Patients ≥80 years old in a single HPB ERAS program (September 2015-July 2018) were prospectively tracked in the ERAS Interactive Audit System (EIAS). Postoperative length of stay (LOS) as well as 30-day major complications, readmissions, and mortality were compared to a pre-ERAS octogenarian control. Since ERAS implementation, octogenarians comprised 7.3% (27 of 370) of patients who underwent pancreaticoduodenectomy (n=17), distal pancreatectomy (n=7), or hepatectomy (n=3). Thirty-day readmissions decreased after ERAS implementation (50% to 15%, P=.037). Thirty-day major complications, mortality, and LOS were similar with 64% median protocol compliance. ERAS for octogenarians in HPB surgery is safe and may contribute to more sustainable recovery resulting in reduced readmissions.

Extracellular Vesicles From the Human Natural Killer Cell Line NK3.3 Have Broad and Potent Anti-Tumor Activity.

Natural killer (NK) cells are critical mediators of immune function, responsible for rapid destruction of tumor cells. They kill primarily through the release of granules containing potent cytolytic molecules. NK cells also release these molecules within membrane-bound exosomes and microvesicles - collectively known as extracellular vesicles (EV). Here we report the characterization and anti-tumor function of EVs isolated from NK3.3 cells, a well described clonal normal human NK cell line. We show that NK3.3 EVs contain the cytolytic molecules perforin, granzymes A and B, and granulysin, and an array of common EV proteins. We previously reported that the E3 ubiquitin ligase, natural killer lytic-associated molecule (NKLAM), is localized to NK granules and is essential for maximal NK killing; here we show it is present in the membrane of NK3.3 EVs. NK3.3-derived EVs also carry multiple RNA species, including miRNAs associated with anti-tumor activity. We demonstrate that NK3.3 EVs inhibit proliferation and induce caspase-mediated apoptosis and cell death of an array of both hematopoietic and non-hematopoietic tumor cell lines. This effect is tumor cell specific; normal cells are unaffected by EV treatment. By virtue of their derivation from a healthy donor and ability to be expanded to large numbers, NK3.3 EVs have the potential to be an effective, safe, and universal immunotherapeutic agent.

Natural Killer Lytic-Associated Molecule (NKLAM): An E3 Ubiquitin Ligase With an Integral Role in Innate Immunity.

Natural Killer Lytic-Associated Molecule (NKLAM), also designated RNF19B, is a unique member of a small family of E3 ubiquitin ligases. This 14-member group of ligases has a characteristic cysteine-rich RING-IBR-RING (RBR) domain that mediates the ubiquitination of multiple substrates. The consequence of substrate ubiquitination varies, depending on the type of ubiquitin linkages formed. The most widely studied effect of ubiquitination of proteins is proteasome-mediated substrate degradation; however, ubiquitination can also alter protein localization and function. Since its discovery in 1999, much has been deciphered about the role of NKLAM in innate immune responses. We have discerned that NKLAM has an integral function in both natural killer (NK) cells and macrophages in vitro and in vivo. NKLAM expression is required for each of these cell types to mediate maximal killing activity and cytokine production. However, much remains to be determined. In this review, we summarize what has been learned about NKLAM expression, structure and function, and discuss new directions for investigation. We hope that this will stimulate interest in further exploration of NKLAM.

Vertical Compliance: A novel method of reporting patient specific ERAS compliance for real-time risk assessment.

BACKGROUND: ERAS protocol compliance is traditionally measured and reported as 'items compliance' which is retrospective longitudinal adherence of all patients to an index element. Reporting in this manner is restrictive and cannot impact care in real-time. In order to modify behavior effectively and instantaneously, we seek to introduce the novel concept of "vertical compliance". METHODS: Vertical compliance is defined as assessment of an individual's compliance along his/her own surgical pathway as ERAS index items are encountered. Prospectively entered data from the ERAS Interactive Audit System (EIAS) database was queried for all patients who underwent pancreatic or hepatic resections. Individual linear regression models were generated using compliance data from 46 ERAS index items against LOS. Significant items with p value < 0.05 were compiled into multivariable linear regression models; each with a unique coefficient that could be used to predict effect on LOS as well as control for the effect of the other items in the model. RESULTS: Compliance data from 483 patients who underwent pancreatic resections and 292 patients who underwent hepatic resections was compiled. Seven ERAS items for pancreatic resections and six ERAS items for hepatic resections were found to significantly impact LOS. Regression models were created for each of the items in an additive fashion. Calculations to determine predicted LOS as a patient progressed through a pathway was able to be determined. CONCLUSION: Vertical compliance is a novel metric, described in this study, that can provide significant and accurate patient-specific risk prediction to impact care in real-time. This can allow for creation of a variable echelon such that pathway items can be ranked by importance on clinical outcome effect and patient progress can be monitored and altered.