Perioperative Mortality Risk in Patients Undergoing Transoral Robotic Surgery for T1-T2 Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study

The National Cancer Database is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methods used or for the conclusions drawn from these data by the investigators.IntroductionTransoral robotic surgery (TORS) is well established as initial definitive treatment for early-stage oropharyngeal squamous cell carcinoma (OPSCC) as an alternative to radiation therapy with similar survival rates. While proponents of TORS focus on the reduced morbidity of treatment compared to open procedures, shortened hospital admissions and equivalent survival outcomes to non-surgical treatment, there remain concerns over the risk of mortality within the acute perioperative period. Therefore, we sought to determine the 30-day and 90-day perioperative mortality risk using the National Cancer Database.MethodsA retrospective cohort analysis was performed for patients diagnosed with pathologic T1/2 OPSCC between January 1, 2010, and December 31, 2016 that underwent primary surgical treatment with TORS and was not restricted by HPV status. The primary outcome was 30-day perioperative mortality. The secondary outcome was 90-day perioperative mortality. Univariable analysis was used to identify variables associated with 30-day perioperative mortality.ResultsIn total, 4,127 patients (mean [SD; range] age, 59 [9.5; 22-90] years; 3,476 [84%] men and 651 [16%] women) met inclusion criteria. The number of patients with pT1-2 OPSCC undergoing TORS increased three-fold between 2010 (279/4,127; 7%) to 2016 (852/4,127; 21%). The overall 30-day and 90-day perioperative mortality rate for TORS during the study period was 0.6% (23/4,127) and 0.9% (38/4,127), respectively. On univariable analysis (UVA), age≥65 was the only predictor of 30-day perioperative mortality (OR 3.41; 95% CI 1.49-7.81).ConclusionThe overall risk of all cause mortality following TORS for early-stage OPSCC remains low. The risk of mortality is higher in elderly patients and should be considered, in addition to previously established risk factors, during patient selection and counselling.

Association between CHADS2, CHA2DS2-VASc, ATRIA, and Essen Stroke Risk Scores and Unsuccessful Recanalization after Endovascular Thrombectomy in Acute Ischemic Stroke Patients

Background: The CHADS2, CHA2DS2-VASc, ATRIA, and Essen scores have been developed for predicting vascular outcomes in stroke patients. We investigated the association between these stroke risk scores and unsuccessful recanalization after endovascular thrombectomy (EVT). Methods: From the nationwide multicenter registry (Selection Criteria in Endovascular Thrombectomy and Thrombolytic therapy (SECRET)) (Clinicaltrials.gov NCT02964052), we consecutively included 501 patients who underwent EVT. We identified pre-admission stroke risk scores in each included patient. Results: Among 501 patients who underwent EVT, 410 (81.8%) patients achieved successful recanalization (mTICI ≥ 2b). Adjusting for body mass index and p < 0.1 in univariable analysis revealed the association between all stroke risk scores and unsuccessful recanalization (CHADS2 score: odds ratio (OR) 1.551, 95% confidence interval (CI) 1.198–2.009, p = 0.001; CHA2DS2VASc score: OR 1.269, 95% CI 1.080–1.492, p = 0.004; ATRIA score: OR 1.089, 95% CI 1.011–1.174, p = 0.024; and Essen score: OR 1.469, 95% CI 1.167–1.849, p = 0.001). The CHADS2 score had the highest AUC value and differed significantly only from the Essen score (AUC of CHADS2 score; 0.618, 95% CI 0.554–0.681). Conclusion: All stroke risk scores were associated with unsuccessful recanalization after EVT. Our study suggests that these stroke risk scores could be used to predict recanalization in stroke patients undergoing EVT.

A Single Center Study on the Risks of Peri-Intervention Stroke in Thoracic Endovascular Aortic Repair (TEVAR) and Endovascular Abdominal Aortic Repair (EVAR)

(1) Background: The risk factors of peri-intervention stroke (PIS) in thoracic endovascular aortic repair (TEVAR) and endovascular abdominal aortic repair (EVAR) are different. This study aimed to compare the risks of PIS in both interventions. (2) Methods: Patients who had suffered a PIS related to TEVAR or EVAR from January 2008 to June 2015 in Songklanagarind Hospital were selected as the cases, while patients who had not suffered PIS were randomly selected to create a 1:4 case: control ratio for analysis. The associations between the factors from pre- to post-intervention and PISs in TEVAR or EVAR cases were analyzed by univariable analysis (p < 0.1). The independent risks of PIS were identified by multivariable analysis and presented in odds ratios (p < 0.05). (3) Results: A total of 17 (2.2%) out of 777 patients who had undergone TEVAR or EVAR experienced PIS, of which 9/518 (1.7%) and 8/259 (3.1%) cases were in TEVAR and EVAR groups, respectively. PIS developed within the first 24 h in nine (52.9%) cases. Large vessel ischemic stroke or watershed infarctions were the most common etiologies of PIS. The independent risks of PIS were the volume of intra-intervention blood loss (1.99 (1.88–21.12), p < 0.001) in the TEVAR-related PIS, and intervention time (2.16 (1.95–2.37), p = 0.010) and post-intervention hyperglycemia (18.60 (1.60–216.06), p = 0.001) in the EVAR-related PIS. There were no differences in the rate of PIS among the operators, intervention techniques, and status of the interventions performed. (4) Conclusion: The risks of PIS in TEVAR or EVAR in our center were different and possibly independent of the operator expertise and intervention techniques.

Total Knee Arthroplasty following Knee Arthroscopy in Patients over 50

The purpose of this study was to evaluate the conversion rate of knee arthroscopy to ipsilateral total knee arthroplasty (TKA) within 2 years in patients aged 50 or older at the time of arthroscopy. The administrative database from a large, physician-owned orthopaedic practice (>100 surgeons) was queried to identify patients over the age of 50 who had undergone arthroscopic knee surgery between January 1, 2006 and January 2, 2015. The subset of patients who converted to TKA within 2 years after knee arthroscopy was identified and matched by age and sex to a control population that did not convert to TKA. Rates of conversion to TKA were calculated. Prearthroscopic digital radiographs were reviewed and Kellgren–Lawrence (KL) grades were compared among case and control populations. Univariable analyses and multivariable regression analysis were performed. Eight hundred seven of 16,061 (5.02%) patients aged 50 or older were converted to TKA within 2 years following ipsilateral knee arthroscopy. In univariable analysis, the rate of conversion to TKA in patients aged between 50 and 54 was 2.94%, compared with 4.44% in patients aged between 55 and 64, and 8.32% in patients 65 or older (p < 0.0001). Female sex was associated with a higher rate of conversion to TKA in univariable analysis (5.93 vs. 4.02% in males, p < 0.0001). KL grades were higher among patients who converted to TKA compared with those who did not (p < 0.0001). In a multivariable regression model controlling for age, sex, and KL grade, only increased KL grade was associated with increased odds of conversion to TKA. In the appropriately selected older patient, the risk of conversion to TKA within 2 years of knee arthroscopy is low (∼5%). Patients with KL grade 2 or higher at the time of arthroscopy should be counseled on the increased odds of early conversion to TKA.

Clinical Features and Risk Factors for Gastrointestinal Complications in Dogs Treated Surgically for Thoracolumbar Intervertebral Disc Extrusion

Gastrointestinal (GI) complications and their clinical implications are poorly characterized in dogs treated surgically for acute thoracolumbar intervertebral disc extrusion (TL-IVDE). The objective of this retrospective study was to characterize GI signs (including vomiting, diarrhea, melena, and hematochezia) in dogs undergoing hemilaminectomy for acute TL-IVDE. One-hundred and sixteen dogs were included. Frequency, type and severity of GI signs during hospitalization, duration of hospitalization and outcome were obtained from the medical record. Potential risk factors for the development of GI signs were explored using univariable and multivariable analyses. Gastrointestinal signs occurred in 55/116 dogs (47%); 22/55 dogs (40%) had one episode and 21/55 (38%) had ≥5 episodes. Diarrhea was the most common (40/55, 73%) while melena was rare (1/55, 2%). GI signs developed in 8/11 dogs (73%) treated perioperatively with both non-steroidal anti-inflammatories and corticosteroids with or without a washout period and in 25/52 dogs (48%) treated prophylactically with proton pump inhibitors. Median hospitalization was 7 days (4–15 days) vs. 5 days (4–11 days) in dogs with or without GI signs, respectively. Duration of hospitalization was associated with development of any GI signs, diarrhea and more severe GI signs (p = 0.001, 0.005, 0.021, respectively). Pre-operative paraplegia with absent pain perception was identified on univariable analysis (p = 0.005) and longer anesthetic duration on multivariable analysis to be associated with development of more severe GI signs (p = 0.047). In dogs undergoing surgery for acute TL-IVDE, GI signs were common and associated with duration of hospitalization and anesthesia. The influence of specific medications and neurologic severity on development of GI signs requires further investigation.

Warfarin Use Is Associated with Increased Mortality at One Year in Patients with Idiopathic Pulmonary Fibrosis

Rationale. Previous data suggest that warfarin may worsen outcomes in IPF in patients with no indication for anticoagulation when compared to placebo. However, warfarin continues to be widely used for cardiac and thromboembolic indications in this patient population due to unavailability of data comparing warfarin with other anticoagulants in patients with IPF. Objectives. We studied the safety and efficacy of warfarin compared to direct acting oral anticoagulant use in patients with IPF. Methods. We conducted a retrospective cohort study of all patients with IPF who were prescribed warfarin or direct acting oral anticoagulants (DOACs) for cardiac or thromboembolic indications and followed at our institute for their care. Univariate tests and multivariable logistic regression analyses were used for assessing association of variables with outcomes. Results. A total of 73 patients were included in the study with 28 and 45 patients in the warfarin and DOAC groups, respectively. Univariable analysis revealed a significant difference in mortality in one year between warfarin and DOAC groups (7/28 vs. 3/45, p value 0.027). Significantly more patients in the warfarin group suffered an exacerbation that required hospitalization within one year (9/28 vs. 5/45, p value 0.026). Multivariate logistic regression analysis showed that anticoagulation with warfarin was independently associated with mortality at one-year follow-up (OR: 77.4, 95% CI: 5.94–409.3, p value: 0.007). Conclusion. In our study of patients with IPF requiring anticoagulants, we noted statistically significant higher mortality with warfarin anticoagulation when compared to DOAC use. Further larger prospective studies are needed to confirm these findings.

Prevalence and predictors of bradyarrhythmias requiring Permanent Pacing in patients with Anderson-Fabry disease.

Introduction: Bradyarrhythmias are an established red flag for storage cardiac conditions including Anderson-Fabry disease (AFD). The prevalence of bradyarrhythmias requiring a pacemaker (PM) and their timing in AFD is unresolved. We evaluated prevalence and predictors of PM requirement in a large AFD cohort, investigating the occurrence of bradyarrhythmias as initial versus late manifestation. Methods: we retrospectively evaluated 82 consecutive AFD patients referred to our multidisciplinary referral centre from 1994 to 2020 with a median follow up of 6.9 years, identifying those requiring pacing. Univariable analysis was performed to identify cardiac features associated with PM implantantion. Results: Five of 82 (6%) AFD patients required PM implantation (5/39, i.e. 13% of those with cardiac involvement), always in the context of advanced cardiomyopathy. In none, bradyarrhythmias were the presenting feature. Indications included sick sinus syndrome in 3 patients, advanced atrio-ventricular block in 2 patients. QRS prolongation during follow up strongly correlated with the onset of bradyarrhythmias. Conclusions: Severe bradyarrhythmias are relatively frequent in patients with AFD cardiomyopathy, but do not represent a mode of presentation, occurring late in the disease course and always in the context of advanced cardiac involvement. Monitoring QRS variations over time may help to identify patients requiring pacing.

Perceptions of Prognosis Among Patients with Advanced Hematologic Malignancies

Background: Although accurate prognostic understanding is essential for patients to make informed decisions about their care, little is known regarding understanding of life expectancy among patients with blood cancers approaching end of life. We sought to characterize such perceptions in a cohort of patients with advanced blood cancers. Methods: In October 2020, we began a web-based survey of adult patients with hematologic malignancies recruited from two large cancer centers. Eligibility criteria included: (1) age ≥ 18 years, (2) at least 2 outpatient visits at the study centers, and (3) physician-estimated prognosis of six months or less based on the patient's hematologic oncologist answering "no" to the question: "would you be surprised if this patient died in the next six months?" The 12-month version of this question has been shown to correctly estimate death in 68.3% of patients with blood cancers (Hudson KE, JPM 2018). Among other questions, participants were asked how important it was for them to know how cancer might influence the length of their life, with response options on a 4-point scale ranging from "not important at all," to "very important." We also asked participants if anyone on their healthcare team had ever discussed how long they might expect to live with their cancer, and participants' perception of their life expectancy, with response options of "more than 2 years," "one to two years," "7 to 11 months," "1 to 6 months," and "less than 1 month." We then asked about the most important factor in determining their self-reported prognosis. We summarized responses for prognostic perceptions with relative frequencies (%). We also assessed, in univariable analysis, if patients' reports of prognostic discussion with their healthcare team was associated with self-report of prognosis of "more than 2 years." Results: As of July 2021, 102 patients had completed the survey (response rate: 64.6%). The most common diagnosis was acute leukemia (38.2%), followed by lymphoma (30.4%; Table 1). The median time between diagnosis and completion of survey was 26 months. The majority (91.1%) felt it was "moderately" or "very important" to know how cancer might influence their length of life, but only 47.1% recalled a discussion about life expectancy with their healthcare team. Most respondents (65.7%) felt their life expectancy at the time of the survey exceeded 2 years (Figure). In univariable analysis, patients who reported having had a prognostic discussion with their healthcare team were less likely to estimate their own life expectancy to be greater than 2 years compared to patients who did not (48.9% vs. 81.1%, chi-square p =0.0007). Factors cited to be most important by respondents in estimating their prognosis were their "health/how things had been going with their cancer" (35.3%), "information received from their doctor or healthcare team" (29.4%), "attitude or personal beliefs" (16.7%), "their own research" (9.8%), and "stories they heard from other people" (3.9%). Conclusions: In this cohort of blood cancer patients with a physician-estimated prognosis of ≤ 6 months based on the "surprise question," two-thirds had substantially more optimistic views of their prognosis. Our finding that over 80% of individuals who did not recall a prognostic discussion with their healthcare team thought their own life expectancy to be greater than 2 years suggests that lack of prognostic disclosure contributes to the gap between physician and patient perceptions of prognosis. The fact that almost half of patients who did report having such a discussion had overly optimistic views suggests that additional factors are also putative. Figure 1 Figure 1. Disclosures Huntington: Flatiron Health Inc.: Consultancy; TG Therapeutics: Research Funding; Thyme Inc: Consultancy; Bayer: Honoraria; DTRM Biopharm: Research Funding; SeaGen: Consultancy; AstraZeneca: Consultancy, Honoraria; Novartis: Consultancy; Servier: Consultancy; Genentech: Consultancy; AbbVie: Consultancy; Pharmacyclics: Consultancy, Honoraria; Celgene: Consultancy, Research Funding.

Utilizing Clinical Features of Progression to Predict Richter's Syndrome in Patients with CLL Progressing after Ibrutinib

Background: Aggressive lymphoma arising in the setting of chronic lymphocytic leukemia (CLL), known as Richter's syndrome (RS), is associated with poor outcomes with standard of care therapies. There is limited capacity for PET-CT to distinguish patients (pts) who develop RS after ibrutinib (Mato Haematologica 2019). Data on outcomes of pts with RS having previously received ibrutinib is limited. Here we sought to determine if clinical characteristics associated with iwCLL criteria for progression (Hallek Blood 2018) predict the risk of RS and overall survival (OS) in pts treated with ibrutinib. Methods: We conducted a retrospective analysis of pts with CLL treated with ibrutinib from 2010-2019 at The Ohio State University. We identified pts that progressed after ibrutinib and classified the progression by 2018 iwCLL criteria. We then identified who developed RS on or after progression. Risk of developing RS was assessed through Fine and Gray model treating death as the competing risk. OS was measured from time of progression and estimated using Cox model. Results: We analyzed 559 pts who had received ibrutinib for CLL, and identified 179 pts who progressed per iwCLL criteria. 94% of the pts who progressed were relapsed/refractory prior to ibrutinib. 116 pts progressed on ibrutinib, and the median time to progression from ibrutinib start was 40.8 months (mos) (range: 0.2-103.9). 63 pts progressed after stopping ibrutinib due to an adverse event or development of a resistance mutation, and the median time to progression from ibrutinib start for these pts was 28.5 mos (range: 0.7-92.9). Of the 179 pts who progressed, 54 developed RS. Of these 54 pts; 83% had enlarging lymphadenopathy, 9% had an enlarging liver or spleen, 17% had constitutional symptoms, 31% had increasing lymphocytosis, 15%, 15%, and 2% had worsening thrombocytopenia, anemia, or neutropenia respectively. No pts had worsening of CLL in the bone marrow (BM) and 2% had new appearance of other organ involvement. As lymphadenopathy and lymphocytosis were the most common clinical features identified we analyzed them jointly; 61% had lymphadenopathy without lymphocytosis, 9% had lymphocytosis without lymphadenopathy, 22% had both, and 7% had neither. Among pts with RS, median time from progression to RS was 0.4 mos (range: 0-49.3). Nine pts had biopsy confirmed RS on the date of progression. Median time from ibrutinib start to RS was 27.8 mos (range: 0.7-92.9). We performed a univariable analysis to determine whether clinical signs of relapse were associated with subsequent risk of RS, and found that presence of lymphadenopathy without lymphocytosis at progression was significantly associated with risk of RS (HR 3.58, 95% CI 1.44-8.88, p=0.006) (Table 1, Figure 1A). To determine if there was an association between clinical features of progression and OS we evaluated all 179 pts that progressed; 72% had enlarging lymphadenopathy, 10% had an enlarging liver or spleen, 15% had constitutional symptoms, 46% had increasing lymphocytosis, 15%, 17%, and 2% had worsening thrombocytopenia, anemia, or neutropenia respectively, only 2% had worsening of CLL in the BM, and 1% had new appearance of other organ involvement. When analyzed jointly; 45% had lymphadenopathy without lymphocytosis, 20% had lymphocytosis without lymphadenopathy, 26% had both, and 9% had neither. Median OS from progression was 24.4 mos (95% CI: 18.6-45.5), while median OS from RS diagnosis was 4.0 mos (95% CI: 2.1-7.1). Median OS from progression was 15.2 mos (95% CI: 7.8-24.6), and 49.9 mos (95% CI: 20.0-NR) for the lymphadenopathy without lymphocytosis and the lymphocytosis without lymphadenopathy groups respectively (Figure 1B). On univariable analysis lymphadenopathy without lymphocytosis was associated with a shorter OS (Table 1). These findings were maintained on multivariable analysis, with lymphadenopathy without lymphocytosis remaining an independent predictor of OS (HR 2.12, CI 1.17-3.87, p=0.01). Conclusions: Here we show that pts who have received prior ibrutinib for CLL who progress with lymphadenopathy have a higher likelihood of having RS than those pts who progress without lymphadenopathy. Furthermore, pts who progressed with lymphadenopathy without lymphocytosis have a shorter OS. Our data suggests that consideration should be given to perform a biopsy to rule out RS in any pts progressing with lymphadenopathy after receiving ibrutinib therapy for CLL. Figure 1 Figure 1. Disclosures Kittai: Abbvie: Consultancy; Janssen: Consultancy; Bristol-Meyers Squibb: Consultancy. Bhat: Beigene: Consultancy; Onclive: Honoraria; AstraZeneca: Consultancy; Aptitude Health: Honoraria. Bond: Kite/Gilead: Honoraria. Byrd: Pharmacyclics LLC: Research Funding; Acerta Pharma: Research Funding; Genentech, Inc.: Research Funding; Janssen Pharmaceuticals, Inc.: Research Funding. Rogers: Genentech: Consultancy, Research Funding; Janssen: Research Funding; Abbvie: Consultancy, Research Funding; Novartis: Research Funding. Woyach: AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; Gilead Sciences Inc: Other: Data & Safety; AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding.

1006. Association of Development of Pneumonia and Virulence Gene Expression in Acinetobacter baumannii Isolated from Clinical Specimens

Background Not all Acinetobacter baumannii isolated from respiratory specimens are true pathogens. Distinguishing between true pathogens and colonizers is important to initiate early treatment and to reduce the unnecessary prescription of antibiotics. To determine the microbiological factors contributing to the development of A. baumannii pneumonia, we investigated the association between the expression level of known A. baumannii virulence genes such as ompA and hisF and pneumonia. Methods Patients in whose respiratory specimens A. baumannii was identified between January 2018 and January 2019 in a tertiary university hospital were recruited into this study. Relevant radiologic findings and more than 5 days of susceptible antibiotic prescription started within 3 days of bacterial isolation were considered as having pneumonia. The absence of radiologic findings of pneumonia until 7 days after the isolation of A. baumannii was defined as colonization. The expression of ompA and hisF was determined with quantitative reverse-transcription polymerase chain reaction. Host factors known to be associated with pneumonia and expression levels of virulent genes were compared between the groups. Results Overall, 246 patients in whose respiratory specimens A. baumannii was identified were recruited into this study. Among them, 17 and 24 patients were assigned to the pneumonia and colonizer groups, respectively. In the univariable analysis, ompA, ICU stay, and mechanical ventilation were significantly associated with pneumonia (p = 0.03, &lt; 0.01, &lt; 0.01 respectively). In the multivariable analysis, mechanical ventilation was significantly associated with pneumonia (OR = 9.75, p = 0.03). ompA expression was not significantly associated with pneumonia in the multivariable analysis (OR = 1.12, p = 0.75) (Table 1). ompA and hisF were significantly associated with the 30-day in-hospital mortality (p = 0.02, &lt; 0.01). Table 1. Univariable and multivariable analysis of factors related to pneumonia Conclusion The association between increased ompA expression in A. baumannii and the development of pneumonia was not statistically significant after adjusting for patient factors. However, the relatively high expression of ompA in pneumonia patients and their association with increased mortality suggests the need for larger-scale prospective studies to draw a conclusion. Disclosures All Authors: No reported disclosures