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Introduction Optimal venous thromboembolism (VTE) enoxaparin prophylaxis dosing remains elusive. Weight-based (WB) dosing safely increases anti-factor Xa levels without the need for routine monitoring but it is unclear if it leads to lower VTE risk. We hypothesized that WB dosing would decrease VTE risk compared with standard fixed dosing (SFD).Methods Patients from the prospective, observational CLOTT-1 registry receiving prophylactic enoxaparin (n=5539) were categorized as WB (0.45–0.55 mg/kg two times per day) or SFD (30 mg two times per day, 40 mg once a day). Multivariate logistic regression was used to generate a predicted probability of VTE for WB and SFD patients.Results Of 4360 patients analyzed, 1065 (24.4%) were WB and 3295 (75.6%) were SFD. WB patients were younger, female, more severely injured, and underwent major operation or major venous repair at a higher rate than individuals in the SFD group. Obesity was more common among the SFD group. Unadjusted VTE rates were comparable (WB 3.1% vs. SFD 3.9%; p=0.221). Early prophylaxis was associated with lower VTE rate (1.4% vs. 5.0%; p=0.001) and deep vein thrombosis (0.9% vs. 4.4%; p

Abstract Background Profound lymphopenia is an independent predictor of adverse clinical outcomes in sepsis. Interleukin-7 (IL-7) is essential for lymphocyte proliferation and survival. A previous phase II study showed that CYT107, a glycosylated recombinant human IL-7, administered intramuscularly reversed sepsis-induced lymphopenia and improved lymphocyte function. Thepresent study evaluated intravenous administration of CYT107. This prospective, double-blinded, placebo-controlled trial was designed to enroll 40 sepsis patients, randomized 3:1 to CYT107 (10 µg/kg) or placebo, for up to 90 days. Results Twenty-one patients were enrolled (fifteen CYT107 group, six placebo group) at eight French and two US sites. The study was halted early because three of fifteen patients receiving intravenous CYT107 developed fever and respiratory distress approximately 5–8 h after drug administration. Intravenous administration of CYT107 resulted in a two–threefold increase in absolute lymphocyte counts (including in both CD4+ and CD8+ T cells (all p

Objectives Damage control laparotomy (DCL) remains an important tool in the trauma surgeon’s armamentarium. Inconsistency in reporting standards have hindered careful scrutiny of DCL outcomes. We sought to develop a core outcome set (COS) for DCL clinical studies to facilitate future pooling of data via meta-analysis and Bayesian statistics while minimizing reporting bias.Methods A modified Delphi study was performed using DCL content experts identified through Eastern Association for the Surgery of Trauma (EAST) ‘landmark’ DCL papers and EAST ad hoc COS task force consensus.Results Of 28 content experts identified, 20 (71%) participated in round 1, 20/20 (100%) in round 2, and 19/20 (95%) in round 3. Round 1 identified 36 potential COS. Round 2 achieved consensus on 10 core outcomes: mortality, 30-day mortality, fascial closure, days to fascial closure, abdominal complications, major complications requiring reoperation or unplanned re-exploration following closure, gastrointestinal anastomotic leak, secondary intra-abdominal sepsis (including anastomotic leak), enterocutaneous fistula, and 12-month functional outcome. Despite feedback provided between rounds, round 3 achieved no further consensus.Conclusions Through an electronic survey-based consensus method, content experts agreed on a core outcome set for damage control laparotomy, which is recommended for future trials in DCL clinical research. Further work is necessary to delineate specific tools and methods for measuring specific outcomes.Level of evidence V, criteria

Objectives Chronic critical illness (CCI) is a phenotype that occurs frequently in patients with severe injury. Previous work has suggested that inflammatory changes leading to CCI occur early following injury. However, the modifiable factors associated with CCI are unknown. We hypothesized that hypothermia, an early modifiable factor, is associated with CCI.Methods To determine the association of hypothermia and CCI, a secondary analysis of the Inflammation and Host Response to Injury database was performed, and subsequently validated on a similar cohort of patients from a single level 1 trauma center from January 2015 to December 2019. Hypothermia was defined as initial body temperature ≤34.5°C. CCI was defined as death or sustained multiorgan failure ≥14 days after injury. Data were analyzed using univariable analyses with Student’s t-test and Pearson’s χ2 test, and logistic regression. An arrayed genomic analysis of the transcriptome of circulating immune cells was performed in these patients.Results Of the initial 1675 patients, 254 had hypothermia and 1421 did not. On univariable analysis, 120/254 (47.2%) of patients with hypothermia had CCI, compared with 520/1421 (36.6%) without hypothermia who had CCI, p

BackgroundOlder patients account for a significant proportion of patients undergoing colorectal cancer surgery and are vulnerable to a number of preoperative risk factors that are not often present in younger patients. Further, three preoperative risk factors that are more prevalent in older adults include frailty, sarcopenia, and malnutrition. Although each of these has been studied in isolation, there is little information on the interplay between them in older surgical patients. A particular area of increasing interest is the use of urine metabolomics for the objective evaluation of dietary profiles and malnutrition. ObjectiveHerein, we describe the design, cohort, and standard operating procedures of a planned prospective study of older surgical patients undergoing colorectal cancer resection across multiple institutions in the United Kingdom. The objectives are to determine the association between clinical outcomes and frailty, nutritional status, and sarcopenia. MethodsThe procedures will include serial frailty evaluations (Clinical Frailty Scale and Groningen Frailty Indicator), functional assessments (hand grip strength and 4-meter walk test), muscle mass evaluations via computerized tomography morphometric analysis, and the evaluation of nutritional status via the analysis of urinary dietary biomarkers. The primary feasibility outcome is the estimation of the incidence rate of postoperative complications, and the primary clinical outcome is the association between the presence of postoperative complications and frailty, sarcopenia, and nutritional status. The secondary outcome measures are the length of hospital stay, 30-day hospital readmission rate, and mortality rate at days 30 and 90. ResultsOur study was approved by the National Health Service Research Ethics Committee (reference number: 19/WA/0190) via the Integrated Research Application System (project ID: 231694) prior to subject recruitment. Cardiff University is acting as the study sponsor. Our study is financially supported through an external, peer-reviewed grant from the British Geriatrics Society and internal funding resources from Cardiff University. The results will be disseminated through peer-review publications, social media, and conference proceedings. ConclusionsAs frailty, sarcopenia, and malnutrition are all areas of common derangement in the older surgical population, prospectively studying these risk factors in concert will allow for the analysis of their interplay as well as the development of predictive models for those at risk of commonly tracked surgical complications and outcomes. International Registered Report Identifier (IRRID)PRR1-10.2196/16846

Abstract Background Sepsis is an increasingly significant challenge throughout the world as one of the major causes of patient morbidity and mortality. Central to the host immunologic response to sepsis is the increase in circulating myeloid-derived suppressor cells (MDSCs), which have been demonstrated to be present and independently associated with poor long-term clinical outcomes. MDSCs are plastic cells and potentially modifiable, particularly through epigenetic interventions. The objective of this study was to determine how the suppressive phenotype of MDSCs evolves after sepsis in surgical ICU patients, as well as to identify epigenetic differences in MDSCs that may explain these changes. Methods Circulating MDSCs from 267 survivors of surgical sepsis were phenotyped at various intervals over 6 weeks, and highly enriched MDSCs from 23 of these samples were co-cultured with CD3/CD28-stimulated autologous T cells. microRNA expression from enriched MDSCs was also identified. Results We observed that MDSC numbers remain significantly elevated in hospitalized sepsis survivors for at least 6 weeks after their infection. However, only MDSCs obtained at and beyond 14 days post-sepsis significantly suppressed T lymphocyte proliferation and IL-2 production. These same MDSCs displayed unique epigenetic (miRNA) expression patterns compared to earlier time points. Conclusions We conclude that in sepsis survivors, immature myeloid cell numbers are increased but the immune suppressive function specific to MDSCs develops over time, and this is associated with a specific epigenome. These findings may explain the chronic and persistent immune suppression seen in these subjects.

OBJECTIVES/GOALS: Many older sepsis survivors develop chronic critical illness (CCI) with poor outcomes. Sepsis is caused by a dysregulated immune response and biomarkers reflecting PICS. The purpose was to compare serial PICS biomarkers in a) older (versus young) adults and b) older CCI (versus older RAP) patients to gain insight into underlying pathobiology of CCI. METHODS/STUDY POPULATION: Prospective longitudinal study with young (≤ 45 years) and older (≥ 65 years) septic adults who were characterized by a) baseline predisposition, b) hospital outcomes, c) serial SOFA organ dysfunction scores over 14 days, d) Zubrod Performance status at three, six and 12-month follow-up and e) mortality over 12 months. Serial blood samples over 14 days were analyzed for selected biomarkers reflecting PICS. RESULTS/ANTICIPATED RESULTS: Compared to the young, more older adults developed CCI (20% vs 42%) and had markedly worse serial SOFA scores, performance status and mortality over 12 months. Additionally, older (versus young) and older CCI (versus older RAP) patients had more persistent aberrations in biomarkers reflecting inflammation, immunosuppression, stress metabolism, lack of anabolism and anti-angiogenesis over 14 days after sepsis. DISCUSSION/SIGNIFICANCE: Older (versus young) and older CCI (versus older RAP) patient subgroups demonstrate early biomarker evidence of the underlying pathobiology of PICS. The population of older sepsis survivors is need of interventions to lower systemic inflammation and stimulate anabolism to prevent skeletal muscle wasting and disability.

Blood product transfusions are associated with increased morbidity and mortality. The purpose of this study was to determine if implementation of a restrictive protocol for packed red blood cell (PRBC) and fresh frozen plasma (FFP) transfusion safely reduces blood product utilization and costs in a surgical intensive care unit (SICU).We performed a retrospective, historical control analysis comparing before (PRE) and after (POST) implementation of a restrictive PRBC/FFP transfusion protocol for SICU patients. Univariate analysis was utilized to compare patient demographics and blood product transfusion totals between the PRE and POST cohorts. Multivariate logistic regression models were developed to determine if implementation of the restrictive transfusion protocol is an independent predictor of adverse outcomes after controlling for age, illness severity, and total blood products received.829 total patients were included in the analysis (PRE, n=372; POST, n=457). Despite higher mean age (56 vs. 52 years, p=0.01) and APACHE II scores (12.5 vs. 11.2, p=0.006), mean units transfused per patient were lower for both packed red blood cells (0.7 vs. 1.2, p=0.03) and fresh frozen plasma (0.3 vs. 1.2, p=0.007) in the POST compared to the PRE cohort, respectively. There was no difference in inpatient mortality between the PRE and POST cohorts (7.5% vs. 9.2%, p=0.39). There was a decreased risk of urinary tract infections (OR 0.47, 95%CI 0.28-0.80) in the POST cohort after controlling for age, illness severity and amount of blood products transfused.Implementation of a restrictive transfusion protocol can effectively reduce blood product utilization in critically ill surgical patients with no increase in morbidity or mortality.