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AbstractBackgroundThis is Part 3 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy using an enhanced recovery after surgery (ERAS) approach. This paper addresses organizational aspects of care.MethodsExperts in management of the high‐risk and emergency general surgical patient were invited to contribute by the International ERAS® Society. PubMed, Cochrane, Embase, and MEDLINE database searches were performed for ERAS elements and relevant specific topics. Studies were selected with particular attention to randomized clinical trials, systematic reviews, meta‐analyses and large cohort studies, and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations.ResultsComponents of organizational aspects of care were considered. Consensus was reached after three rounds of a modified Delphi process.ConclusionsThese guidelines are based on best current available evidence for organizational aspects of an ERAS® approach to patients undergoing emergency laparotomy and include discussion of less common aspects of care for the surgical patient, including end‐of‐life issues. These guidelines are not exhaustive but pull together evidence on important components of care for this high‐risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.

Abstract Background This is Part 2 of the first consensus guidelines for optimal care of patients undergoing emergency laparotomy (EL) using an Enhanced Recovery After Surgery (ERAS) approach. This paper addresses intra‐ and postoperative aspects of care. Methods Experts in aspects of management of high‐risk and emergency general surgical patients were invited to contribute by the International ERAS ® Society. PubMed, Cochrane, Embase, and Medline database searches were performed for ERAS elements and relevant specific topics. Studies on each item were selected with particular attention to randomized clinical trials, systematic reviews, meta‐analyses, and large cohort studies and reviewed and graded using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Recommendations were made on the best level of evidence, or extrapolation from studies on elective patients when appropriate. A modified Delphi method was used to validate final recommendations. Some ERAS ® components covered in other guideline papers are outlined only briefly, with the bulk of the text focusing on key areas pertaining specifically to EL. Results Twenty‐three components of intraoperative and postoperative care were defined. Consensus was reached after three rounds of a modified Delphi Process. Conclusions These guidelines are based on best available evidence for an ERAS ® approach to patients undergoing EL. These guidelines are not exhaustive but pull together evidence on important components of care for this high‐risk patient population. As much of the evidence is extrapolated from elective surgery or emergency general surgery (not specifically laparotomy), many of the components need further evaluation in future studies.

8567 Background: Adjuvant osimertinib (osi) improves disease-free survival (DFS) in patients (pts) with resected, early-stage, EGFR-mutant (EGFRmut) NSCLC, yet the benefit of osi after CRT in pts with unresectable locally advanced NSCLC is unknown. Post-hoc analysis of the PACIFIC trial showed a lack of survival benefit with consolidation durva versus placebo in pts with EGFRmut NSCLC. Comparisons between consolidation durva and EGFR TKIs in unresectable EGFRmut NSCLC following CRT are lacking. Methods: We conducted a multi-institutional retrospective analysis of pts with stage III unresectable EGFRmut NSCLC (exon19 deletion, exon21 L858R), who received EGFR TKI or durva after ≥ 2 cycles of platinum-based chemotherapy plus definitive radiation therapy between 2015-2022. Baseline characteristics including age, sex, smoking history, PD-L1 status, and outcomes on DFS, overall survival (OS), and safety were collected. Multivariable (MVA) cox regression analysis was used for statistical analysis. Treatment-related adverse events (trAE) were defined using CTCAE 5.0. Results: Seventeen pts from 12 institutions received an EGFR TKI (osi, n=15; erlotinib, n=2), and 13 pts received consolidation durva. Median follow-up was 23 months. Median age of all pts was 61 years (IQR:52-72) and 76.7% were female. Most pts in both groups had never-smoked and had adenocarcinoma. All pts received ≥ 60 Gy of radiation with concurrent chemotherapy. PD-L1 expression was ≥ 50% in 1/10 (10%) pts treated with durva vs 6/13 (46.2%) treated with TKI, p=0.09. Median duration on treatment for EGFR TKI and durva was 12.2 months and 4.8 months, respectively. Pts treated with EGFR TKI had significantly longer 24-month DFS versus pts treated with durva after adjusting for stage (3A vs 3B vs 3C) (Table). Any grade tRAE occurred in 58.8% (10/17) of pts treated with EGFR TKI vs 38.5% (5/13) with durva. Grade > 3 tRAE occurred in 15.4% (1 pneumonitis and 1 AST/ALT elevation) of pts treated with durva but in none of pts treated with EGFR TKI. Three pts within each arm came off treatment due to toxicity (EGFR TKI: 1 pneumonitis and 2 dermatitis; durva: 1 of each pneumonitis, Type 1 diabetes, AST/ALT elevation). Conclusions: EGFR TKI therapy after definitive CRT was associated with significantly longer DFS compared to durva in this retrospective study of pts with stage III unresectable EGFRmut NSCLC, without unanticipated safety signals. Follow-up is ongoing and OS outcomes will be evaluated subsequently. Further investigation is warranted to define the optimal therapy for locally advanced EGFRmut NSCLC. [Table: see text]

5074 Background: Analysis of phase 3 studies of patients (pts) with mHSPC in the era of ADT, including in combination with docetaxel and/or androgen receptor axis targeted therapies have established PSA-7mo as a key prognostic marker. Our objective was to evaluate the association between PSA-3mo, PSA 7-mo and OS measured in the phase 3 S1216 trial in mHSPC comparing ADT + orteronel (treatment arm) vs ADT + bicalutamide (control arm) [NCT01809691]. Methods: Pts enrolled in the S1216 trial with available PSA-3mo & PSA-7mo were included in this analysis. PSA responses were defined as complete response (CR) if PSA ≤ 0.2 ng/mL, partial response (PR) for PSA >0.2 and ≤ 4ng/mL, and no response (NR) as PSA >4 ng/mL at month 3 or 7. Landmark OS was measured and Cox regression model applied adjusting for stratification (performance status, extent of disease, early vs late start of treatment, treatment arm). Results: 1251 pts were alive and evaluable for PSA-3mo and 1231 pts were evaluable at 7 mo, out of a total of 1279 pts. The median age was 67 (range: 43-92), 10% of patients were black, 96% had a Zubrod performance status of 0-1. Median PSA at baseline was 29 ng/ml (range: 2-6710). Of pts on treatment vs.control arm, PSA-3mo CR, PR, and NR occurred in 52% vs 35%; 31% vs 42%, and 17% vs 23%, respectively. Of pts on treatment vs control arm, PSA-7mo CR, PR, and NR occurred in 61% vs 46%, 20% vs 26%, and 19% vs 29%, respectively. CR or PR at either timepoint led to significantly better outcomes than those with NR. No interaction between treatment arm and PSA response was observed in terms of OS. Conclusions: PSA-3mo and PSA-7mo are strong prognostic markers for pts with mHSPC. More pts on ADT with orteronel achieved CR at 3 and 7 mo. In addition to its use in counseling patients in the clinic, PSA-3mo and PSA-7mo may be used as parameters for designing future trials in pts with mHSPC, utilizing the next generation of intensification or de-intensification treatment regimens. Clinical trial information: NCT01809691 . [Table: see text]

Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.

Background: The 18-item Glasgow Benefit Inventory (GBI) has been widely used to measure patient general health response to otorhinolaryngologic and facial plastic interventions. The GBI was recently reorganized into 15 questions with 5 sub-scale factors ( GBI-5F) to improve its utility. Application of the GBI-5F to septal perforation treatments may improve our understanding of quality of life outcomes. Methodology/Principal: The GBI was given to patients seen from August 2018 through October 2021 who were at least 6 months postoperative attempted perforation surgical closure using bilateral nasal mucosal flaps with an interposition graft. Original GBI and GBI-5F scores were computed and subgroup analysis performed in this retrospective medical record review. Results: Of the 98 patients (mean age 45.5 years) who met study criteria, 65 were female. Mean perforation length was 12.9, and height 9.7 mm. The mean postoperative time to GBI completion was 12.7 months. Highest GBI-5F scores were noted in the Quality of Life factor, followed by Self-confidence and Social Involvement. Females reported significantly higher scores than men. Total GBI scores were similar to those recorded for other rhinologic procedures. Conclusions: The GBI-5F provides measurable insight into patient quality of life benefit following septal perforation repair.

OBJECTIVE The American Spine Registry (ASR) is a collaborative effort between the American Academy of Orthopaedic Surgeons and the American Association of Neurological Surgeons. The goal of this study was to evaluate how representative the ASR is of the national practice with spinal procedures, as recorded in the National Inpatient Sample (NIS). METHODS The authors queried the NIS and the ASR for cervical and lumbar arthrodesis cases performed during 2017–2019. International Classification of Diseases, 10th Revision and Current Procedural Terminology codes were used to identify patients undergoing cervical and lumbar procedures. The two groups were compared for the overall proportion of cervical and lumbar procedures, age distribution, sex, surgical approach features, race, and hospital volume. Outcomes available in the ASR, such as patient-reported outcomes and reoperations, were not analyzed due to nonavailability in the NIS. The representativeness of the ASR compared to the NIS was assessed via Cohen’s d effect sizes, and absolute standardized mean differences (SMDs) of < 0.2 were considered trivial, whereas > 0.5 were considered moderately large. RESULTS A total of 24,800 arthrodesis procedures were identified in the ASR for the period between January 1, 2017, and December 31, 2019. During the same time period, 1,305,360 cases were recorded in the NIS. Cervical fusions comprised 35.9% of the ASR cohort (8911 cases) and 36.0% of the NIS cohort (469,287 cases). The two databases presented trivial differences in terms of patient age and sex for all years of interest across both cervical and lumbar arthrodeses (SMD < 0.2). Trivial differences were also noted in the distribution of open versus percutaneous procedures of the cervical and lumbar spine (SMD < 0.2). Among lumbar cases, anterior approaches were more common in the ASR than in the NIS (32.1% vs 22.3%, SMD = 0.22), but the discrepancy among cervical cases in the two databases was trivial (SMD = 0.03). Small differences were illustrated in terms of race, with SMDs < 0.5, and a more significant discrepancy was identified in the geographic distribution of participating sites (SMDs of 0.7 and 0.74 for cervical and lumbar cases, respectively). For both of these measures, SMDs in 2019 were smaller than those in 2018 and 2017. CONCLUSIONS The ASR and NIS databases presented a very high similarity in proportions of cervical and lumbar spine surgeries, as well as similar distributions of age and sex, and distribution of open versus endoscopic approach. Slight discrepancies in anterior versus posterior approach among lumbar cases and patient race, and more significant discrepancies in geographic representation were also identified, yet decreasing trends in differences suggested the improving representativeness of the ASR over the course of time and its progressive growth. These conclusions are important to underline the external validity of quality investigations and research conclusions to be drawn from analyses in which the ASR is used.

ABSTRACT Although physical activity (PA) is crucial in the prevention and clinical management of nonalcoholic fatty liver disease, most individuals with this chronic disease are inactive and do not achieve recommended amounts of PA. There is a robust and consistent body of evidence highlighting the benefit of participating in regular PA, including a reduction in liver fat and improvement in body composition, cardiorespiratory fitness, vascular biology, and health-related quality of life. Importantly, the benefits of regular PA can be seen without clinically significant weight loss. At least 150 min of moderate or 75 min of vigorous intensity PA are recommended weekly for all patients with nonalcoholic fatty liver disease, including those with compensated cirrhosis. If a formal exercise training program is prescribed, aerobic exercise with the addition of resistance training is preferred. In this roundtable document, the benefits of PA are discussed, along with recommendations for 1) PA assessment and screening; 2) how best to advise, counsel, and prescribe regular PA; and 3) when to refer to an exercise specialist.