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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.

607 Background: Immunotherapy (IO) is known to have robust anti-tumor activity in patients with MSI-H solid tumors. However, clinical trials investigating IO activity have used tissue-based testing to determine MSI-H status. Pancreatic tumor biopsy often does not provide sufficient tumor tissue for MSI testing. We investigated if the MSI-H status detected by plasma-based circulating tumor DNA (ctDNA) testing predicts robust response to IO in patients with PC. Methods: Genomic results from a well-validated plasma-based ctDNA assay (Guardant360[G360]) performed as part of routine clinical care between October 1, 2018 and September 7, 2021 in patients with PC were queried to identify patients with MSI-H tumors. Patient characteristics, tumor characteristics, treatment details, and outcomes were reported by ordering clinicians where available. The data cut-off date was September 1, 2021. Results: A total of 52 patients with PC who had MSI-H tumors on G360 were identified. Clinical outcomes data were available for 10/52 (19%) patients who were included for analysis. This patient cohort had a median age of 68 years (range: 56-82); 80% were male and 80% of patients had metastatic disease. 9/10 patients received IO: 3 in the first-line, 3 in the second-line, 3 in the third-line setting; most received pembrolizumab (8/9) while 1 received ipilimumab plus nivolumab. The median duration of IO was 8 months (range: 1-24). The overall response rate was 77% (7/9) and 6 of the 7 responders continue to show response at the time of data cut-off after a median follow-up of 21 months (range:11-33). The median progression-free survival and overall survival were not reached in the IO-treated cohort. Tissue-based MSI testing results were concordant with plasma-based G360 results in 5 of 6 patients (83%) who had tissue-based test results available. The patient with the discordant result was MSI-H by G360 but had intact mismatch repair protein expression by immunohistochemistry. This patient received neoadjuvant IO followed by surgery and the resected specimen confirmed pathological complete response. Conclusions: The detection of MSI-H status by plasma-based ctDNA testing is highly concordant to tissue-based testing and predicts robust and durable response to IO in patients with PC. The use of a well-validated plasma-based ctDNA analysis may expand the identification of MSI-H tumors in patients with PC and enable treatment with IO resulting in improved outcomes.

Background: Rheumatoid arthritis (RA) affecting the metacarpophalangeal (MCP) joint may warrant arthroplasty. The purpose of this study was to investigate implant survivorship, complications, radiographic outcomes, and clinical outcomes in patients undergoing MCP arthroplasty with a pyrocarbon implant to treat RA. Methods: In all, 124 MCP joint pyrocarbon arthroplasties in 40 patients performed to treat RA were reviewed. Operations were at the index (n = 43, 35%), middle (n = 33, 27%), ring (n = 27, 22%), and small (n = 21, 17%) fingers from 1998 to 2009 in 105 (85%) female and 19 (15%) male joints with a mean age of 54 ± 11 years. Mean postoperative follow-up was 6 ± 3 years. All patients achieved at least 2 years of follow-up. Results: Rates of implant survivorship at 1, 2, 5, and 10 years were 98%, 98%, 90%, and 81%, respectively. Fifteen percent (n = 18) of arthroplasties underwent revision at a mean 5 ± 3 years postoperatively. The overall reoperation rate was 29% (n = 36). Rates of survival from reoperation at 1, 2, 5, and 10 years were 85%, 84%, 76%, and 68%, respectively. Complications occurred in 32% (n = 40). Pain ratings improved postoperatively ( P < .01). Arc of motion improved from 37 ± 21 to 43 ± 19 ( P = .03). Both appositional and oppositional strength improved after surgery; however, there was no improvement in grip strength ( P < .01). Conclusions: Metacarpophalangeal arthroplasty with a pyrocarbon implant demonstrated reliable improvement in pain and arc of motion in patients with RA. Complication and overall reoperation rates were high, while 1 in 10 undergo revision within 5 years postoperatively.

Purpose: Outpatient visits and surgeries for nonurgent indications in ophthalmology have intermittently been restricted during the COVID-19 pandemic. Telemedicine services have rapidly gained acceptance during this period, and could improve patient access for routine oculoplastic evaluations in the future. The objective of this study is to investigate interobserver and intraobserver reliability of eyelid and brow position assessment and surgical plan when comparing photography-based and face-to-face evaluation. Methods: This was an observational study conducted at a single academic center. Thirty randomly selected patients who had completed an in-office evaluation for chief complaint of “drooping eyelids” between June 2019 and March 2020 were included. Virtual assessment of brow position, dermatochalasis, blepharoptosis, and margin-reflex distance 1 was performed by 2 oculoplastic surgeons based on external photographs, and a surgical plan was formulated. Fraction of agreement and Cohen’s κ were determined to evaluate reliability of the virtual assessment compared to face-to-face examination. Results: For 60 eyes from 30 study subjects, diagnostic reliability for observer A was near perfect for brow ptosis, substantial for blepharoptosis and moderate for dermatochalasis (κ = 0.86, 0.67, and 0.57, respectively); for observer B, reliability was moderate for brow and blepharoptosis and substantial for dermatochalasis (0.47, 0.59, and 0.79). Fraction of agreement for blepharoptosis was 94% in eyes where the eyelid margin was visible, and 66% in eyes where the eyelid margin was obscured by overhanging skin. Virtual margin-reflex distance 1 measurements were highly correlated with those obtained face to face (r = 0.77, p < 0.01). Fraction of agreement for surgical plan after virtual examination by observer A/B, respectively, was 100%/94% for brow lift, 90%/87% for blepharoptosis repair and 83%/83% for functional upper blepharoplasty. Conclusions: Virtual evaluation of upper eyelid and brow malposition can be performed with acceptable reliability. Co-existing dermatochalasis or brow ptosis may require special photographic technique or video examination to ensure an appropriate diagnosis. A photography-based preliminary surgical plan offers a viable alternative to face-to-face encounters.

PURPOSE Distant metastases are present in 6% or more of patients with newly diagnosed breast cancer. In this context, locoregional therapy for the intact primary tumor has been hypothesized to improve overall survival (OS), but clinical trials have reported conflicting results. METHODS Women presenting with metastatic breast cancer and an intact primary tumor received systemic therapy for 4-8 months; if no disease progression occurred, they were randomly assigned to locoregional therapy for the primary site (surgery and radiotherapy per standards for nonmetastatic disease) or continuing sysmetic therapy. The primary end point was OS; locoregional control and quality of life were secondary end points. The trial design provided 85% power to detect a 19.3% absolute difference in the 3-year OS rate in randomly assigned patients. The stratified log-rank test and Cox proportional hazards model were used to compare OS between arms. Cumulative incidence of locoregional progression was compared using Gray's test. Quality-of-life assessment used standard instruments. RESULTS Of 390 participants enrolled, 256 were randomly assigned: 131 to continued systemic therapy and 125 to early locoregional therapy. The 3-year OS was 67.9% without and 68.4% with early locoregional therapy (hazard ratio = 1.11; 90% CI, 0.82 to 1.52; P = .57). The median OS was 53.1 months (95% CI, 47.9 to not estimable) in the systemic therapy arm and 54.9 months (95% CI, 46.7 to not estimable) in the locoregional therapy arm. Locoregional progression was less frequent in those randomly assigned to locoregional therapy (3-year rate: 16.3% v 39.8%; P < .001). Quality-of-life measures were largely similar between arms. CONCLUSION Early locoregional therapy for the primary site did not improve survival in patients presenting with metastatic breast cancer. Although it was associated with improved locoregional control, this had no overall impact on quality of life.

AbstractPreclinical data demonstrated that combining an anti–programmed cell death 1 (PD-1) inhibitor with a cyclin-dependent kinase 9 (CDK9) inhibitor provided enhanced antitumor activity with no significant toxicities, suggesting this combination may be a potential therapeutic option. The multicohort, phase 1 KEYNOTE-155 study evaluated the safety and antitumor activity of the PD-1 inhibitor pembrolizumab plus the CDK9 inhibitor dinaciclib in patients with relapsed or refractory (rr) chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM). Patients enrolled were ≥18 years of age with a confirmed diagnosis of CLL, DLBCL, or MM. The study included 2 phases: a dose-evaluation phase to determine dose-limiting toxicities and a signal-detection phase. Patients received pembrolizumab 200 mg every 3 weeks plus dinaciclib 7 mg/m2 on day 1 and 10 mg/m2 on day 8 of cycle 1 and 14 mg/m2 on days 1 and 8 of cycles 2 and later. Primary endpoint was safety, and a key secondary endpoint was objective response rate (ORR). Seventy-two patients were enrolled and received ≥1 dose of study treatment (CLL, n = 17; DLBCL, n = 38; MM, n = 17). Pembrolizumab plus dinaciclib was generally well tolerated and produced no unexpected toxicities. The ORRs were 29.4% (5/17, rrCLL), 21.1% (8/38, rrDLBCL), and 0% (0/17, rrMM), respectively. At data cutoff, all 72 patients had discontinued treatment, 38 (52.8%) because of progressive disease. These findings demonstrate activity with combination pembrolizumab plus dinaciclib and suggest that a careful and comprehensive approach to explore anti–PD-1 and CDK9 inhibitor combinations is warranted. This trial was registered at www.clinicaltrials.gov as NCT02684617.