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Background The American Association for the Surgery of Trauma (AAST) has developed a grading system for emergency general surgery (EGS) conditions. We sought to validate the AAST EGS grades for patients undergoing urgent/emergent colorectal resection. Methods Patients enrolled in the “Eastern Association for the Surgery of Trauma Multicenter Colorectal Resection in EGS—to anastomose or not to anastomose” study undergoing urgent/emergent surgery for obstruction, ischemia, or diverticulitis were included. Baseline demographics, comorbidity severity as defined by Charlson comorbidity index (CCI), procedure type, and AAST grade were prospectively collected. Outcomes included length of stay (LOS) in-hospital mortality, and surgical complications (superficial/deep/organ-space surgical site infection, anastomotic leak, stoma complication, fascial dehiscence, and need for further intervention). Multivariable logistic regression models were used to describe outcomes and risk factors for surgical complication or mortality. Results There were 367 patients, with a mean (± SD) age of 62 ± 15 years. 39% were women. The median interquartile range (IQR) CCI was 4 (2-6). Overall, the pathologies encompassed the following AAST EGS grades: I (17, 5%), II (54, 15%), III (115, 31%), IV (95, 26%), and V (86, 23%). Management included laparoscopic (24, 7%), open (319, 87%), and laparoscopy converted to laparotomy (24, 6%). Higher AAST grade was associated with laparotomy ( P = .01). The median LOS was 13 days (8-22). At least 1 surgical complication occurred in 33% of patients and the mortality rate was 14%. Development of at least 1 surgical complication, need for unplanned intervention, mortality, and increased LOS were associated with increasing AAST severity grade. On multivariable analysis, factors predictive of in-hospital mortality included AAST organ grade, CCI, and preoperative vasopressor use (odds ratio (OR) 1.9, 1.6, 3.1, respectively). The American Association for the Surgery of Trauma emergency general surgery grade was also associated with the development of at least 1 surgical complication (OR 2.5), while CCI, preoperative vasopressor use, respiratory failure, and pneumoperitoneum were not. Conclusion The American Association for the Surgery of Trauma emergency general surgery grading systems display construct validity for mortality and surgical complications after urgent/emergent colorectal resection. These results support incorporation of AAST EGS grades for quality benchmarking and surgical outcomes research.

Abstract Background Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 (Gal-2) blockade in ischemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Gal-2 may also affect other macrophage-related cardiovascular diseases. Objectives This study aims to elucidate the effects of Gal-2 inhibition in atherosclerosis. Methods ApoE −/− mice were given a high-cholesterol diet (HCD) for 12 weeks. After 6 weeks of HCD, intermediate atherosclerotic plaques were present. To study the effects of anti-Gal-2 nanobody treatment on the progression of existing atherosclerosis, treatment with two llama-derived anti-Gal-2 nanobodies (clones 2H8 and 2C10), or vehicle was given for the remaining 6 weeks. Results Gal-2 inhibition reduced the progression of existing atherosclerosis. Atherosclerotic plaque area in the aortic root was decreased, especially so in mice treated with 2C10 nanobodies. This clone showed reduced atherosclerosis severity as reflected by a decrease in fibrous cap atheromas in addition to decreases in plaque size.The number of plaque resident macrophages was unchanged; however, there was a significant increase in the fraction of CD206+ macrophages. 2C10 treatment also increased plaque α-smooth muscle content, and Gal-2 may have a role in modulating the inflammatory status of smooth muscle cells. Remarkably, both treatments reduced serum cholesterol concentrations including reductions in very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein while triglyceride concentrations were unchanged. Conclusion Prolonged and frequent treatment with anti-Gal-2 nanobodies reduced plaque size, slowed plaque progression, and modified the phenotype of plaque macrophages toward an anti-inflammatory profile. These results hold promise for future macrophage modulating therapeutic interventions that promote arteriogenesis and reduce atherosclerosis.

AbstractBackgroundA reliable history is critical to establish accurate clinical diagnoses, prioritize investigations and select appropriate treatments; yet few studies have considered the factors that influence the reliability of medical histories. Recognizing this, we determined the accuracy of medical history in community‐dwelling older adults engaged in longitudinal studies of memory and aging.MethodThe association between participant‐specific factors and accurate reporting of stroke or diabetes were evaluated using multivariable logistic regression in 1,401 participants enrolled in studies at the Knight Alzheimer Disease Research Center (Saint Louis, Missouri), including 425 participants with dementia (30.3%). History was verified with a reliable collateral source in all participants. Stroke and diabetes were selected as index variables, as gold standard measures—brain MRI for stroke and hemoglobinA1c (HbA1c) for diabetes—were routinely obtained in participants.Result25/862 (2.9%) participants endorsed a history of stroke, which was confirmed on MRI in 8/25 (positive predictive value, 17.4%). Stroke was detected on MRI in 38/837 (4.5%) of those without reported stroke (negative predictive value, 95.5%). Older age (OR per decade=1.7, 95%CI: 1.2‐2.5) and use of an unrelated collateral source (OR=2.0, 95%CI: 1.03‐3.7) were associated with greater odds of inaccurate reporting of stroke history. 190/1322 (14.4%) participants reported a history of diabetes, which was confirmed with HbA1c in 105/190 (positive predictive value, 55.3%). HbA1c 6.5% was detected in 29/1132 (2.6%) of those who denied diabetes (negative predictive value, 97.4%). African Americans (OR=1.6, 95%CI: 1.02‐2.6) and those with hypertension (OR=2.6, 95%CI: 1.5‐4.2) or HbA1c compatible with impaired glucose tolerance (OR=4.2, 95%CI: 2.7‐6.4) had greater odds of reporting a history of diabetes. Cognitive impairment was not associated with inaccurate reporting of stroke or diabetes.ConclusionThe accuracy of reported history of diabetes and stroke was low in older community‐dwelling participants, independent of cognitive status. A history of diabetes or stroke should be objectively confirmed when relevant to decision making in clinical and research settings.

AbstractBackgroundWhile parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC.MethodsPatients from the US HIPEC Collaborative (2000–2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0‐1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS).ResultsA total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non‐LR patients. LR patients had decreased OS (2‐year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10–11.81), colorectal histology (HR, 3.84; 95% CI, 1.69–12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21–9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2‐year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%).ConclusionsAs CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

AbstractBackgroundVariations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers.MethodsData from the US HIPEC Collaborative represents a retrospective multi‐institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed‐effects linear (continuous outcomes) or logistic (binary outcomes) regression models.ResultsA total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8‐70.9) and readmissions (overall 20.6%, range: 8.9‐33.3) varied by institution (P < .001). Institution‐level variation in perioperative practice patterns existed among measured ERAS pathway process/outcomes (P < .001). The percentages of variation with each process/outcome measure attributable solely to institutional practices ranged from 0.6% to 66.6%.ConclusionsSignificant variation exists in the perioperative care of patients undergoing CRS/HIPEC at major US academic institutions. These findings provide a strong rationale for the investigation of best practices in CRS/HIPEC patients.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

PURPOSE Primary endocrine therapy for ductal carcinoma in situ (DCIS) as a potential alternative to surgery has been understudied. This trial explored the feasibility of a short-term course of letrozole and sought to determine whether treatment results in measurable radiographic and biologic changes in estrogen receptor (ER)–positive DCIS. PATIENTS AND METHODS A phase II single-arm multicenter cooperative-group trial was conducted in postmenopausal patients diagnosed with ER-positive DCIS without invasion. Patients were treated with letrozole 2.5 mg per day for 6 months before surgery. Breast magnetic resonance imaging (MRI) was obtained at baseline, 3 months, and 6 months. The primary end point was change in 6-month MRI enhancement volume compared with baseline. RESULTS Overall, 79 patients were enrolled and 70 completed 6 months of letrozole. Of these, 67 patients had MRI data available for each timepoint. Baseline MRI volumes ranged from 0.004 to 26.3 cm 3 . Median reductions from baseline MRI volume (1.4 cm 3 ) were 0.6 cm 3 (61.0%) at 3 months ( P < .001) and 0.8 cm 3 (71.7%) at 6 months ( P < .001). Consistent reductions were seen in median baseline ER H-score (228; median reduction, 15.0; P = .005), progesterone receptor H-score (15; median reduction, 85.0; P < .001), and Ki67 score (12%; median reduction, 6.3%; P = .007). Of the 59 patients who underwent surgery per study protocol, persistent DCIS remained in 50 patients (85%), invasive cancer was detected in six patients (10%), and no residual DCIS or invasive cancer was seen in nine patients (15%). CONCLUSIONS In a cohort of postmenopausal women with ER-positive DCIS, preoperative letrozole resulted in significant imaging and biomarker changes. These findings support future trials of extended endocrine therapy as primary nonoperative treatment of some DCIS.

Abstract Abstract 5045 Observation remains the standard approach to patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic multiple myeloma (AMM) who lack end-organ impairment characteristic of symptomatic MM. Institution of early MM therapy has not been shown to improve survival or alter the natural progression of the disease. Cyclooxygenase-2 (COX2) inhibitors inhibit proliferation and induce apoptosis in drug resistant MM cell lines. 23 asymptomatic adult patients with a serum monoclonal protein >1g/dL, from Cleveland Clinic, Mayo Clinic, or University of Arkansas Medical Center between August 2005 and April 2008 were randomized to either celecoxib or placebo in a double-blind, 1:1 fashion. The primary end point was change in the monoclonal protein concentration after 6 months. Correlative biomarkers, including IL6 and IL-6R, CD4/CD8+ T-cell ratios, and beta-2 microglobulin, were examined before and after treatment. Celecoxib had no significant effect on the median monoclonal protein concentration, which went from a median of 1. 44 to 1. 65 g/dL with placebo and 2. 42 to 2. 24 g/dL with Celecoxib (p=0. 36), or on any of the analyzed correlative markers (all p-values >0. 34). One patient's monoclonal protein concentration increased on placebo, but he did not require treatment for symptomatic MM. There were no adverse events of Grade 2 or higher. Celecoxib was well tolerated in contrast to previous reports when given in higher doses and in combination with thalidomide. Although accrual was limited we conclude that celecoxib has no clinical or immunologic effect on high risk asymptomatic plasma cell disorders. This study does not support using celecoxib for preventing progression to symptomatic MM. Future studies on progression of MGUS to symptomatic MM would require more patients and a longer follow-up period. Disclosures: Off Label Use: Celecoxib for chemoprophylaxis. Hussein:Celgene: Employment. Reu:Celgene: Research Funding.

Abstract Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART ) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross‐PIA white paper that provides both a concise “state‐of‐the‐science” report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.