Citations

6514 Background: Tobacco use is a modifiable risk factor for adverse outcomes among patients diagnosed with cancer. Despite ASCO’s recommendation for assessment and treatment of tobacco use, integration into cancer care is suboptimal. Socioeconomic contexts influence access and utilization of tobacco treatment, but little is known about the relationship between neighborhood socioeconomic disadvantage (NSD) and tobacco assessment, assistance, and cessation among cancer patients enrolled in clinical trials. Methods: The NCI Cancer Patient Tobacco Use Questionnaire (C-TUQ) was centrally administered to participants enrolled in 10 ECOG ACRIN clinical trials (9 therapeutic, 1 imaging). We examined associations of NSD with patient-reported rates of receiving brief tobacco cessation support (i.e., Ask, Assist (counseling)) and cessation (past 30d quit attempts and duration). NSD was measured using the national Area Deprivation Index (ADI) based on participant’s zip code. Associations between ADI (low, intermediate, and high) and tobacco variables were evaluated using logistic regression and ANOVA. Results: 740 patients, completing the C-TUQ between June 2017-October 2021, can be classified as 402 (54%) never smokers, 81 (11%) current smokers, and 257 (35%) former smokers. Patients were 70% male; 94% white; 3% Hispanic; mean age 58.8 (SD 9.0). Cancer diagnoses were 36% leukemia; 19% lymphoma, 18% prostate, 11% breast; 9% melanoma, 7% myeloma, and 0.5% head and neck. Patients were categorized into high (33%), intermediate (34%) and low (33%) disadvantaged neighborhoods. Patients in high (vs. low) disadvantaged neighborhoods were more likely to report being asked about smoking (OR = 3.90; 95% CI (confidence interval), 1.61 to 9.46; p = 0.0062) but less likely to report receiving counseling to help quit smoking (OR = 0.20; 95% CI, 0.06 to 0.73; p = 0.0234). Patients from high disadvantaged neighborhoods had the shortest quit duration, followed by patients from intermediate and low disadvantaged neighborhoods (mean = 145.78, 187.66, and 210.98 months, respectively, p = 0.0372). Conclusions: Greater socioeconomic neighborhood disadvantage was associated with increased assessment of tobacco use but decreased tobacco treatment referral, and the shortest quit duration. More research is needed to promote increased referral to tobacco treatment for individuals with cancer from disadvantaged neighborhoods to promote and sustain cessation.

Study Design: Retrospective cohort study. Objective: The purposes of this study were to determine the rate of improvement of significant preoperative weakness, identify risk factors for failure to improve, and characterize the motor recovery of individual motor groups. Summary of Background Data: While neck and arm pain reliably improve following anterior cervical discectomy and fusion (ACDF), the frequency and magnitude of motor recovery following ACDF remain unclear. Methods: We performed a retrospective review of patients undergoing 1–4-level ACDF at a single institution between September 2015 and June 2016. Patients were subdivided into 2 groups based upon the presence or absence of significant preoperative weakness, which was defined as a motor grade <4 in any single upper extremity muscle group. Clinical notes were reviewed to determine affected muscle groups, rates of motor recovery, and risk factors for failure to improve. Results: We identified 618 patients for inclusion. Significant preoperative upper extremity weakness was present in 27 patients (4.4%). Postoperatively, 19 of the affected patients (70.3%) experienced complete strength recovery, and 5 patients (18.5%) experienced an improvement in muscle strength to a motor grade ≥4. The rate of motor recovery postoperatively was 85.7% in the triceps, 83.3% in the finger flexors, 83.3% in the hand intrinsics, 50.0% in the biceps, and 25.0% in the deltoids. Risk factors for failure to experience significant motor improvement were the presence of myelomalacia (odds ratio: 28.9, P<0.01) and the performance of >2 levels of ACDF (odds ratio: 10.1, P<0.01). Conclusions: Patients with substantial preoperative upper extremity weakness can expect high rates of motor recovery following ACDF, though patients with deltoid weakness, myelomalacia, and >2 levels of ACDF are less likely to experience significant motor improvement.

PURPOSE Antitumor activity in preclinical models and a phase I study of patients with dedifferentiated liposarcoma (DD-LPS) was observed with selinexor. We evaluated the clinical benefit of selinexor in patients with previously treated DD-LPS whose sarcoma progressed on approved agents. METHODS SEAL was a phase II-III, multicenter, randomized, double-blind, placebo-controlled study. Patients age 12 years or older with advanced DD-LPS who had received two-five lines of therapy were randomly assigned (2:1) to selinexor (60 mg) or placebo twice weekly in 6-week cycles (crossover permitted). The primary end point was progression-free survival (PFS). Patients who received at least one dose of study treatment were included for safety analysis (ClinicalTrials.gov identifier: NCT02606461 ). RESULTS Two hundred eighty-five patients were enrolled (selinexor, n = 188; placebo, n = 97). PFS was significantly longer with selinexor versus placebo: hazard ratio (HR) 0.70 (95% CI, 0.52 to 0.95; one-sided P = .011; medians 2.8 v 2.1 months), as was time to next treatment: HR 0.50 (95% CI, 0.37 to 0.66; one-sided P < .0001; medians 5.8 v 3.2 months). With crossover, no difference was observed in overall survival. The most common treatment-emergent adverse events of any grade versus grade 3 or 4 with selinexor were nausea (151 [80.7%] v 11 [5.9]), decreased appetite (113 [60.4%] v 14 [7.5%]), and fatigue (96 [51.3%] v 12 [6.4%]). Four (2.1%) and three (3.1%) patients died in the selinexor and placebo arms, respectively. Exploratory RNA sequencing analysis identified that the absence of CALB1 expression was associated with longer PFS with selinexor compared with placebo (median 6.9 v 2.2 months; HR, 0.19; P = .001). CONCLUSION Patients with advanced, refractory DD-LPS showed improved PFS and time to next treatment with selinexor compared with placebo. Supportive care and dose reductions mitigated side effects of selinexor. Prospective validation of CALB1 expression as a predictive biomarker for selinexor in DD-LPS is warranted.

Abstract Melioidosis, an infection caused by Burkholderia pseudomallei, has a very high risk of mortality when treated, with an even higher risk of fatality if undiagnosed or not treated appropriately. It is endemic to Asia, Australia, South America, and the Caribbean; however, the number of melioidosis cases reported in the United States has been increasing. Therefore, physicians should be aware of this clinical entity and its possible presentations. Mycotic aneurysms due to B. pseudomallei are extremely rare, accounting for ~1%–2% of cases. Here we describe a rare case of melioidosis presenting as a mycotic aneurysm in the United States, highlight the potential for diagnostic challenges and epidemiologic concerns, and provide a review of mycotic aneurysm cases due to B. pseudomallei published to date.

Open reading frame 8 (ORF8) shows one of the highest levels of variability among accessory proteins in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19). It was previously reported that the ORF8 protein inhibits the presentation of viral antigens by the major histocompatibility complex class I (MHC-I), which interacts with host factors involved in pulmonary inflammation. The ORF8 protein assists SARS-CoV-2 in evading immunity and plays a role in SARS-CoV-2 replication. Among many contributing mutations, Q27STOP, a mutation in the ORF8 protein, defines the B.1.1.7 lineage of SARS-CoV-2, engendering the second wave of COVID-19. In the present study, 47 unique truncated ORF8 proteins (T-ORF8) with the Q27STOP mutations were identified among 49,055 available B.1.1.7 SARS-CoV-2 sequences. The results show that only one of the 47 T-ORF8 variants spread to over 57 geo-locations in North America, and other continents, which include Africa, Asia, Europe and South America. Based on various quantitative features, such as amino acid homology, polar/non-polar sequence homology, Shannon entropy conservation, and other physicochemical properties of all specific 47 T-ORF8 protein variants, nine possible T-ORF8 unique variants were defined. The question as to whether T-ORF8 variants function similarly to the wild type ORF8 is yet to be investigated. A positive response to the question could exacerbate future COVID-19 waves, necessitating severe containment measures.

Background: Left ventricular assist device (LVAD) implantation is a new therapy for advanced heart failure (HF). The number of HF patients eligible for LVAD and the cardiology providers’ comfort level with referral for LVAD remains unclear. Objective: To assess provider perception of LVAD candidacy and LVAD referral patterns in consecutive HF patients. Methods: Providers completed a survey for each HF patient seen between March 1, 2013 and April 26, 2013. The survey listed standard LVAD candidacy criteria and asked 1) if a patient was an LVAD candidate (yes, no, unsure); 2) reasons patients were not LVAD candidates (check list, table); and 3) whether the patient had been referred for LVAD evaluation (yes, no, unsure). Results: Patients (n=522) were seen in a tertiary HF outpatient clinic (n=357; 68%), a tertiary HF inpatient service (n=36; 7%), a tertiary general cardiology service (n=45; 9%) or a community based outpatient cardiac clinic (n=84; 16%) Median age of patients was 73 years and 65% were male. Provider assessment of LVAD candidacy was “no” in 443 (85%), “yes” in 35 (7%) and “unsure” in 43 (8%) with ineligibility for LVAD attributed to multiple concerns (Table). Ninety percent of patients considered “too old” for LVAD were over 78 years of age. Provider designation of LVAD candidacy as yes or unsure varied across practice setting: tertiary HF outpatient clinic, 12%; tertiary HF inpatient service, 42%; tertiary general cardiology service, 22%; and community based outpatient cardiac clinic, 13%. In patients with a provider designation of LVAD candidacy as yes or unsure (n=78), only 21 (27%) patients had been referred for LVAD evaluation. Conclusion: When provided with LVAD candidacy criteria, providers indicated 15% of HF patients were (7%) or were possibly (8%) LVAD candidates but indicated that few patients had undergone a formal LVAD evaluation. These data suggest that measures to improve evaluation of HF patients for LVAD are needed.

Background: Heart failure (HF) is a clinical syndrome with an overall poor prognosis, but the clinical trajectory is often unpredictable in individuals. There has been an impetus to promote iterative patient-provider discussions regarding preferences for end of life (EOL) care and advanced care planning. However, very little is known regarding provider preferences or their personal confidence addressing EOL care with their patients with HF. To address these gaps in knowledge, we surveyed clinicians at three practice sites in a large integrated health system. Methods: Physicians, nurse practitioners (NP), and physician assistants (PA) at Mayo Clinic (Rochester, Minnesota) and its surrounding health system were asked to participate in an electronic survey in October 2013. Clinicians surveyed included tertiary care HF specialists (Tertiary Care Cardiology), cardiologists and NP/PAs practicing in a community setting (Community Cardiology), and primary care clinicians (Primary Care). Results: A total of 95 clinicians completed the survey (52.5% response rate), including 50 physicians and 45 NP/PAs. Clinicians reported discussing prognosis and EOL wishes when their patient’s health status was worsening, but only 12% reported annual discussions as advocated by the American Heart Association. In total 52% of providers reported one or more reasons that they hesitate to discuss EOL care with their patients, including provider discomfort (11%), perception of patient (21%) or family (12%) unreadiness to have the discussion, fear of destroying hope (9%), or a lack of time (8%). Tertiary Care (63%) and Community Cardiology (58%) clinicians were more likely to attribute responsibility for having EOL discussions to the HF cardiologist, while 66% of Primary Care providers felt it was their responsibility. Tertiary and Community Cardiology clinicians were more likely to have referred patients to Palliative Medicine within the last year than Primary Care (89% vs. 21%, p<0.001). Overall, 30% of those surveyed reported low or very low confidence levels in initiating prognosis or EOL discussions, enrolling patients in hospice, or providing EOL care, with lower confidence among those with fewer years of clinical experience. The majority of clinicians expressed a high level of interest in further skills acquisition on these topics. Conclusion: There is tremendous variability in the way that clinicians view and approach advanced care discussions with their patients with HF; varying provider perception and lack of provider confidence may contribute. Despite this variability, most clinicians are interested in further development and skills acquisition. Addressing the learning needs of providers is an important next step toward enhancing the EOL care of patients with HF.