Citations

e16193 Background: Liver transplantation (LT) is curative for hepatocellular carcinoma (HCC) in patients within the Milan criteria. Readmissions are common postoperatively, and can be associated with increased morbidity and healthcare burden. Hence we aim to identify incidence, impact and independent predictors for readmission in patients who underwent LT in HCC. Methods: Retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for LT with an underlying diagnosis of HCC, in patients with cirrhosis we used the BAVENO score to categorize between compensated and decompensated cirrhosis. We aim to identify 30-day readmission rate, mortality, healthcare related utilization resources and independent predictors of readmission. Results: A total of 2,092 patients with HCC underwent liver transplantation. The 30-day readmission rate was 25.6%. Main causes for readmission were post-surgical complications from LT, sepsis, liver failure. Readmitted patients were less likely to have private insurance (40.5% vs 34.5%; P<0.01), to be obese (18.2% vs 7.9%; P<0.01), hypertensive (51.2% vs 39.5%; P<0.01), have history of non-alcoholic steatohepatitis (16.5% vs 2.3%; P<0.01). Readmission was associated with higher in-hospital mortality rate (0.1% vs. 1.5%; P<0.01). The total health care in-hospital economic burden of readmission was $56.1 million in total charges and $15.2 million in total costs. Independent predictors of readmission were type 2 diabetes, transfusion of blood products during index admission, protein-caloric malnutrition, sepsis, and preventive factors were younger age, private insurance and cannabis use. Conclusions: Readmissions after LT in HCC are associated with higher mortality and pose a high health care burden. We identified risk factors that can be targeted to decrease overall patient morbidity, mortality and health care burden.[Table: see text]

e16109 Background: Total gastrectomy with lymph node dissection is curative for early gastric malignancy which accounts for 1.5% of cancer cases in the U.S. Readmissions are common postoperatively, and are associated with increased morbidity, mortality, hospital costs and decreased quality of life. We hence aim to identify incidence, impact and independent predictors for readmission in patients who underwent total gastrectomy in gastric malignancy. Methods: We conducted a retrospective cohort study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for total gastrectomy with a concomitant diagnosis of gastric malignancy. T-test was used for continuous variables and chi square test was used for categorical variables. Multivariate regression was used to identify predictors for unplanned readmissions. ICD 10 codes were used to identify diagnoses and procedures. Results: A total of 1,779 patients with gastric malignancy underwent total gastrectomy. The 30-day readmission rate was 18.5%. Main causes for readmission were sepsis, ventricular fibrillation, recurrent STEMI. Readmitted patients were more likely to be on chemotherapy. (40.1% vs 27.2%; P<0.01) and more likely to be discharged to a skilled facility (13.5% vs 17.9%; P<0.01). The total health care in-hospital economic burden of readmission was $6.5 million in total charges and $25 million in total costs. Independent predictors of readmission were major bleeding, respiratory failure requiring mechanical ventilation, peripheral parenteral nutrition, history of non-alcoholic hepato-steatosis, and prolonged length of stay. Conclusions: Readmissions after gastrectomy in patients with gastric malignancies are associated with lower in-hospital mortality yet pose a substantial economic burden on healthcare. The lower mortality might be explained by the relatively stable course and lower comorbidities of patients who become eligible for discharge after surgery. Further studies are suggested. Modifiable risk factors like malnutrition and sepsis warrant special attention to decrease readmissions and improve overall outcomes.[Table: see text]

2500 Background: Oncolytic virotherapy is a novel immunomodulatory therapeutic approach for relapsed refractory hematologic malignancies. The Indiana strain of Vesicular Stomatitis Virus was engineered to encode interferon beta (IFNβ) and sodium iodine symporter (NIS) to produce VSV-IFNβ-NIS. Virally encoded IFNβ serves as an index of viral proliferation and enhances host anti-tumor immunity. NIS was inserted to noninvasively assess viral biodistribution using SPECT/PET imaging. We present the results of the phase 1 clinical trial NCT03017820 of systemic administration of VSV-IFNβ-NIS among patients (pts) with relapsed refractory Multiple Myeloma (MM), T cell Lymphoma (TCL) and Acute myeloid Leukemia (AML). Methods: VSV-IFNβ-NIS was administered at 5x109 TCID50 (50% tissue culture infectious dose) dose level 1 to dose level 4, 1.7x1011 TCID50. The primary objective was to determine the maximum tolerated dose of VSV-IFNβ-NIS as a single agent. Secondary objectives were determination of safety profile and preliminary efficacy of VSV-IFNβ-NIS. Correlative objectives included monitoring viremia and virus shedding. Adverse events (AEs) are reported based on CTCAE V4; cytokine release syndrome (CRS) grading was based on Lee (Blood 2014) criteria. Results: 15 pts received VSV-IFNβ-NIS: MM (7), TCL(7) and AML(1); 3 pts were treated at each dose level (DL) 1 through 3 (respectively 0.05, 0.17, and 0.5 x 1011 TCID50), & 6 pts were treated at dose level 4 (1.7x1011 TCID50). There were no dose limiting toxicities. The most frequent grades 3 & 4 AEs were hematologic: lymphopenia (46.6 & 26.6%), neutropenia (13.3% & 6.7%). CRS grades 1 (6.7%) and 2 (46.6%) were the non-hematologic AEs of note; mostly at DL 4. Only 1 pt required transient pressor support. Responses were seen in pts with T cell lymphoma. At DL2, there was a partial response (PR) lasting 3 months in a pt, post 12 prior lines of therapy. At DL4 there was a 6 month PR in a pt with PTCL and another pt with cutaneous relapse of PTCL who enjoys an ongoing CR, more than 1 year post VSV infusion; both pts received 5 prior lines of therapy. Viremia was detected in all pts at the end of infusion only up to 72 hrs post infusion; no infectious virus was recovered in buccal swabs or urine. Neutralizing anti-VSV antibodies were present by day 29. IFN levels were detectable within 30 mins of infusion, peaking between 4 & 48 hrs. TCL pts mounted higher hIFNβ levels within 48 hrs; the pt with CR mounted peak hIFNβ response of 18213.3pg/ml at 48 hrs post infusion, 15-fold higher than any other pt. Conclusions: VSV-IFNβ-NIS can be safely administered by IV infusion among heavily pretreated pts with hematologic malignancies. VSV-IFNβ-NIS as a single agent appears to be most effective at DL4 among patients with TCL, with an ongoing CR in a patient at DL4 more than 1 year post administration. Future trials of combination strategies with immune-modulatory drugs are currently being planned. Clinical trial information: NCT03017820.

Purpose To describe double radial tears of the lateral meniscus (LM), report early clinical treatment outcomes, and determine reoperation and failure rates. Methods Twenty‐one (N = 21) consecutive cases of arthroscopic‐treated lateral meniscus double radial tears treated between 2012 and 2018 were reviewed, including 15 males (71.4%) and 6 females (28.6%). Meniscus repairs were all performed at the time of anterior cruciate ligament (ACL) reconstruction. Patients with associated fractures or prior surgeries were excluded. Concomitant injuries were reported, as were preinjury and postoperative Tegner scores, preoperative and postoperative visual analogue pain scale (VAS) scores, and postoperative International Knee Documentation Committee (IKDC) subjective scores. Reoperation and failure rates were documented. Results Twenty‐one (N = 21) tears were located in the posterior horn of the meniscus near the root attachment; 15 (71.4%) underwent all‐inside repair, 4 (19.0%) underwent transtibial pull‐through repair, 1 (4.8%) was partially debrided, and 1 (4.8%) was left untreated. Twenty‐one tears (N = 21) were in the body of the meniscus; 7 (33.3%) were repaired, 7 (33.3%) were partially debrided, and 7 (33.3%) were left untreated. Thirteen patients (62%) had associated medial collateral ligament (MCL) injuries. Mean follow‐up was 2.6 years. VAS at rest and with activity improved by 2.1 points ( P < .001) and 3.1 points ( P = .017) after surgery. The mean postoperative Tegner activity score was 6.4, and the mean IKDC score was 83.2 at final follow‐up. Reoperation was required in 5 patients (23.8%), and the surgical treatment failed in 1 patient (4.7%). Conclusions Double radial tears of the LM are uncommon injuries that occur in the setting of ACL tears, usually combined with MCL injury. The variety of surgical treatment techniques have a low failure rate at short‐term follow‐up. Patients tend to have good clinical outcomes with improvement in pain and overall function after surgically treating these injuries with simultaneous ACL reconstruction. Level of Evidence Level IV, therapeutic study, case series

Background: Several professional society guidelines suggest holding antiplatelet agents before high-risk procedures. However, there is lack of high-grade evidence to support the recommendation as most of the studies have been single center with small sample sizes. We aimed to perform the first systematic review and meta-analysis comparing dual antiplatelet therapy (DAPT) versus aspirin alone in terms of postendoscopic retrograde cholangiopancreatography (ERCP) bleeding. Methods Three independent reviewers performed a comprehensive review of all original articles published from inception to May 2020, evaluating the post-ERCP bleeding rate in setting of DAPT. Primary outcomes were the overall post-ERCP bleeding rate with the use of dual antiplatelet therapy; comparison of post-ERCP bleeding rate in patients with DAPT versus aspirin alone. Secondary outcomes were comparison of immediate and delayed post-ERCP bleeding outcomes in the 2 cohorts. Results: Six studies were included after a thorough search was concluded using the key words. The pooled analysis of studies revealed an overall post-ERCP bleeding rate of 5.7% (95% confidence interval: 3-10.6) on sustained DAPT. Post-ERCP bleeding in DAPT Cohort was not significantly higher as compared with aspirin only Cohort (odds ratio: 1.14, 95% confidence interval: 0.46-2.81). The immediate bleeding and delayed bleeding rates cannot be generalized due to low number of studies. Conclusions: The first systematic review and meta-analysis showed that post-ERCP bleeding rates are not significantly higher in DAPT cohort as compared with aspirin alone. Therefore, the risk of bleeding is less likely related to the antiplatelet agents and more likely related to the procedure itself.

Abstract Objective Diazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness. Methods A long‐term, phase 3, open‐label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen. Results Among 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no‐benzodiazepine group. Findings were similar in a sub‐analysis of patients who were ( n = 44) or were not ( n = 75) taking clobazam. Significance This analysis of patients from a long‐term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub‐analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.

Purpose To identify features of instruments, test procedures, study design, and validity evidence in published studies of electrocardiogram (ECG) skill assessments. Method The authors conducted a systematic review, searching MEDLINE, Embase, Cochrane CENTRAL, PsycINFO, CINAHL, ERIC, and Web of Science databases in February 2020 for studies that assessed the ECG interpretation skill of physicians or medical students. Two authors independently screened articles for inclusion and extracted information on test features, study design, risk of bias, and validity evidence. Results The authors found 85 eligible studies. Participants included medical students (42 studies), postgraduate physicians (48 studies), and practicing physicians (13 studies). ECG selection criteria were infrequently reported: 25 studies (29%) selected single-diagnosis or straightforward ECGs; 5 (6%) selected complex cases. ECGs were selected by generalists (15 studies [18%]), cardiologists (10 studies [12%]), or unspecified experts (4 studies [5%]). The median number of ECGs per test was 10. The scoring rubric was defined by 2 or more experts in 32 studies (38%), by 1 expert in 5 (6%), and using clinical data in 5 (6%). Scoring was performed by a human rater in 34 studies (40%) and by computer in 7 (8%). Study methods were appraised as low risk of selection bias in 16 studies (19%), participant flow bias in 59 (69%), instrument conduct and scoring bias in 20 (24%), and applicability problems in 56 (66%). Evidence of test score validity was reported infrequently, namely evidence of content (39 studies [46%]), internal structure (11 [13%]), relations with other variables (10 [12%]), response process (2 [2%]), and consequences (3 [4%]). Conclusions ECG interpretation skill assessments consist of idiosyncratic instruments that are too short, composed of items of obscure provenance, with incompletely specified answers, graded by individuals with underreported credentials, yielding scores with limited interpretability. The authors suggest several best practices.

PURPOSE New technology might pose problems for older patients with cancer. This study sought to understand how a trial in older patients with cancer (Alliance A171603) was successful in capturing electronic patient-reported data. METHODS Study personnel were invited via e-mail to participate in semistructured phone interviews, which were audio-recorded and qualitatively analyzed. RESULTS Twenty-four study personnel from the 10 sites were interviewed; three themes emerged. The first was that successful patient-reported electronic data capture shifted work toward patients and toward study personnel at the beginning of the study. One interviewee explained, “I mean it kind of lost all advantages…by being extremely laborious.” Study personnel described how they ensured electronic devices were charged, wireless internet access was up and running, and login codes were available. The second theme was related to the first and dealt with data filtering. Study personnel described high involvement in data gathering; for example, one interviewee described, “I answered on the iPad, whatever they said. They didn't even want to use it at all.” A third theme dealt with advantages of electronic data entry, such as prompt data availability at study completion. Surprisingly, some remarks described how electronic devices brought people together, “Some of the patients, you know, it just gave them a chance to kinda talk about, you know, what was going on.” CONCLUSION High rates of capture of patient-reported electronic data were viewed favorably but occurred in exchange for increased effort from patients and study personnel and in exchange for data that were not always patient-reported in the strictest sense.

Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children’s Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.