Citations

LBA7564 Background: Patients with r/r B-NHL have a dismal prognosis. DIAL (Dual Immunomodulation in Aggressive Lymphoma) was a multi-center randomized phase II study testing the efficacy of nivolumab (PD-1 inhibitor) plus varlilumab (CD27 agonist) in this population. Methods: Patients were randomized (1:1) to nivolumab (240 mg IV every 2 weeks for 4 months, 480 mg IV monthly thereafter; group 1) alone or combined with varlilumab (3 mg/kg IV monthly; group 2). Cross-over (group 1 to 2) was allowed for progression. Primary endpoint was overall response (ORR) per LYRIC criteria. A sample size of 48 patients per arm would provide 80% power to detect increase in ORR from 25% to 45% using a one-sided test (p = 0.15). Pre-specified interim analysis occurred after half of the patients completed first radiologic assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Exploratory endpoints included tumor genomic assessment and immune profiling of blood and tumor. Results: 53 patients were enrolled (27 in group 1; 26 in group 2). Interim analysis included 24 patients from each arm. Mean age was 65.2 years, 34 (70.8%) were male, and 36 (75%) received prior CAR-T cell therapy. Baseline characteristics were balanced between arms. Grade ≥ 3 AEs were observed in 8 (33.3%) and 7 (30.4%) of patients in groups 1 and 2, respectively. Common AEs (> 5%) of any grade included fatigue, lymphopenia, diarrhea, rash. There were no treatment-associated deaths. Toxicity profile was similar between arms. Table summarizes efficacy outcomes. ORR was achieved in 6 patients (12.5%), not statistically different between arms; 4 responses were complete. Seven patients crossed over (1 responded after crossing). Median OS (8.6 vs 7.3 months; p = 0.39) and PFS (2.7 vs 1.4 months; p = 0.06) were similar between arms. Subgroup analysis of patients with prior CAR-T cell therapy showed similar ORR (5/36; 14%), not statistically different between arms. Correlative analysis results will be presented at conference. The trial met futility criterion on interim analysis and enrollment ceased based on pre-specified stopping rule. Conclusions: Dual immunomodulatory therapy did not enhance anti-tumor activity in patients with aggressive B-NHL compared to nivolumab alone. Response rates were low and consistent with previous data using PD-1 inhibitors in this population. Prior therapy with CAR-T cell does not seem to sensitize patients to PD-1 blockade. Toxicity profile was acceptable and dual therapy did not increase the rate of AEs. Clinical trial information: NCT03038672. [Table: see text]

Abstract Rationale The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia (n = 20) and with respiratory failure and histologic DAD (n = 21; non–COVID-19 viral and nonviral etiologies). Premortem chest computed tomography (CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion (CVasc) in different microscopic compartments. Respiratory mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. Histopathology revealed vasculopathic changes, including hemangiomatosis-like changes (P = 0.043), thromboemboli (P = 0.0038), pulmonary infarcts (P = 0.047), and perivascular inflammation (P < 0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc range (P = 0.002). Alveolar-septal congestion was associated with a significantly shorter time to death from symptom onset (P = 0.03), length of hospital stay (P = 0.02), and increased ventilatory ratio [an estimate for pulmonary dead space fraction (Vd); p = 0.043] in all cases of ARDS. Conclusions Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.

Introduction Coronavirus disease 2019 accelerated the use of virtual visits within health care. We examined the utility of telemedicine for conducting visits in a tertiary head and neck practice. Methods A retrospective study was conducted on patients presenting via video to a tertiary-level head and neck clinic between January 2020 and December 2020. Patient demographics were collected in addition to visit indication, diagnostic imaging/tests at the time of visit, and post-visit plan. Visits were deemed successful if evaluation by video was sufficient in determining a clinical plan and did not require deferment of recommendations for subsequent in-person consult visits and/or work-up (labs, imaging). Logistic regression was performed to identify variables that served as significant predictors of successful video visits. Results A total of 124 video visits were reviewed. Video visits were successful for the initial evaluation 88.7% of the time ( n = 110). Computerized tomographic scans were the most available diagnostic test, available for 54% of patients ( n = 67), followed by biopsy report 30.6% ( n = 38). Visit indication had a statistically significant effect on whether a treatment plan could be made ( p = 0.024). For new patients with parotid masses ( n = 42), definitive treatment plans could be made 97.6% of the time ( n = 41). Patients presenting with an indication of thyroid mass (odds ratio: 0.19 (confidence interval: 0.00072–0.50), p = 0.018) and other neck mass (odds ratio: 0.035 (confidence interval: 0.0014, 0.90), p = 0.043) were at significantly lesser odds than parotid patients to have a successful video visit. Discussion In this study, virtual visits were successful for a high percentage of head and neck visits, particularly among patients seeking evaluation for parotid-related concerns.

PURPOSE This investigation sought to evaluate the prognostic value of pretreatment of circulating tumor DNA (ctDNA) in metastatic biliary tract cancers (BTCs) treated with platinum-based first-line chemotherapy treatment. MATERIALS AND METHODS We performed a retrospective analysis of 67 patients who underwent ctDNA testing before platinum-based chemotherapy for first-line treatment for metastatic BTC. For analysis, we considered the detected gene with highest variant allele frequency as the dominant clone allele frequency (DCAF). Results of ctDNA analysis were correlated with patients' demographics, progression-free survival (PFS), and overall survival (OS). RESULTS The median age of patients was 67 (27-90) years. Fifty-four (80.6%) of 67 patients evaluated had intrahepatic cholangiocarcinoma; seven had extrahepatic cholangiocarcinoma, and six gallbladder cancers. Forty-six (68.6%) of the patients were treated with cisplatin plus gemcitabine, and 16.4% of patients received gemcitabine and other platinum (carboplatin or oxaliplatin) combinations, whereas 15% of patients were treated on a clinical trial with gemcitabine and cisplatin plus additional agents (CX4945, PEGPH20, or nab-paclitaxel). TP53, KRAS, FGFR2, ARID1A, STK11, and IDH1 were the genes with highest frequency as DCAF. The median DCAF was 3% (0%-97%). DCAF > 3% was associated with worse OS (median OS: 10.8 v 18.8 months, P = .032). Stratifying DCAF in quartiles, DCAF > 10% was significantly related to worse PFS (median PFS: 3 months, P = .014) and worse OS (median OS: 7.0 months, P = .001). Each 1% increase in ctDNA was associated with a hazard ratio of 13.1 in OS when adjusting for subtypes, metastatic sites, size of largest tumor, age, sex, and CA19-9. CONCLUSION DCAF at diagnosis of advanced BTC can stratify patients who have worse outcomes when treated with upfront platinum-based chemotherapy. Each increase in %ctDNA decreases survival probabilities.

AbstractSeizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody‐positive neuromyelitis optica spectrum disorder (AQP4‐NMOSD), and myelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4‐NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune‐associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4‐NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)‐like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM‐like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4‐NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most‐updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4‐NMOSD/MOGAD. Treatment cautions including drug‐drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

Background and Aims: The impact of disease progression in NAFLD on liver outcomes remains poorly understood. We aimed to investigate NAFLD progression using longitudinal liver stiffness measurements (LSM) by serial magnetic resonance elastography (MRE) and the association with liver outcomes. Approach and Results: All adult patients with NAFLD who underwent at least two serial MREs for clinical evaluation at Mayo Clinic, Rochester, between 2007 and 2019 were identified from the institutional database. Progression and regression were defined based on LSM change of 19% above or below 19% of initial LSM, respectively, based on Quantitative Imaging Biomarker Alliance consensus. The association between change in LSM and liver‐related outcomes occurring after the last MRE was examined using time‐to‐event analysis. A total of 128 participants underwent serial MREs (53% female, median age 59 years). The median time between paired MREs was 3.4 (range 1–10.7) years. NAFLD progression (LSM = +0.61 kPa/year) was identified in 17 patients (13.3%). NAFLD regression (−0.40 kPa/year) occurred in 35 patients (27.3%). Stable LSM was noted in 76 participants (59.4%). In NAFLD without cirrhosis at baseline ( n = 75), cirrhosis development occurred in 14% of LSM progressors and 2.9% of non‐progressors ( p = 0.059) over a median 2.7 years of follow‐up from the last MRE. Among those with compensated cirrhosis at baseline MRE ( n = 29), decompensation or death occurred in 100% of LSM progressors and 19% of non‐progressors ( p < 0.001) over a median 2.5 years of follow‐up after the last MRE. Conclusions: Noninvasive monitoring of LSM by conventional MRE is a promising method of longitudinal NAFLD monitoring and risk estimation of liver‐related outcomes in NAFLD.

Abstract Introduction COVID-19 primarily affects the respiratory system, however, a number of clinical sequela have emerged in patients recovered from COVID-19. Besides the most commonly reported symptoms of fatigue and dyspnea, early studies have found that sleep disturbance is also a common complaint. The aim of this study is to survey for sleep disturbance, degree of fatigue and daytime sleepiness in a group of post-hospitalized COVID-19 patients. Methods Patients who were discharged from Mayo Clinic hospitals after COVID-19 hospitalization were recruited in this study. Patients who have an existing diagnosis of sleep apnea or other sleep disorders were excluded from this study. Mayo Clinic patients who never had COVID-19 infection, nor a history of sleep disorders or other sleep disorders were also recruited as controls. Patients completed Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale (FSS) questionnaires via REDCap. Wilcoxon rank sum test was used to evaluate the difference between cases and controls in continuous variables and Fisher’s exact test was used to compare categorical variables. Multivariable linear regression model was used to evaluate the difference in sleep and fatigue scores between cases and controls with baseline characters adjusted. All tests were two-sided with p value &lt;0.05 considered statistically significant. Results A total of 62 patients who completed the questionnaires were included in the analysis. Among them, 33 had COVID-19. Cases were significantly older with higher BMI compared to controls. Global PSQI score (median=10 vs 6, p=0.015), ESS total score (median=8 vs 5, p=0.018) and FSS total score (median=30 vs 22, p=0.009) were all significantly higher for cases compared to control patients. After adjusting for age and BMI, the difference stayed statistically significant. The mean difference between cases vs controls was found to be 2.7 (95%CI:0.2-5.2, p=0.038), 2.93 (95% CI: 0.66-5.2, p=0.014), and 12.62 (95% CI:5.22-20.03, p=0.001) for PSQI, ESS, and FSS scores, respectively. Conclusion Preliminary results showed that sleep disturbance (PSQI) and daytime symptoms (measured by ESS and FSS) are found to be significantly higher among post COVID-19 hospitalized patients compared to controls. Support (If Any) This work is supported by the Mayo Clinic in Florida Department of Medicine Catalyst for Advancing in Academics award and the Mayo Clinic in Florida Research Accelerator for Clinicians Engaged in Research Program.

Introduction We examined the suitability of using a video visit platform to perform postoperative parotidectomy evaluation at a tertiary care, multiple-surgeon otolaryngology center. Methods A retrospective case review was conducted of patients who underwent parotidectomy and postoperative video visits between November 2019 and December 2020. Success of video visit, plan if applicable, and post-visit outcomes were reviewed. Video visits were designated as successful if the physician could assess for complications in the postoperative course (e.g. first bite pain, Frey syndrome, ear numbness, unplanned visits to the emergency department, unplanned return to the operating room), perform examination of facial nerve function, and formulate care recommendations per clinical judgement without deferment of recommendations for a subsequent in-person visit. Results There were 96 postoperative video visits with 91 unique parotidectomy patients. Demographics: 28/63 male/female; average age, 54y. All video visits were suitable for successful postoperative parotidectomy patient evaluation. Eight visits (8.3%) consisted of patients presenting with common postoperative complications (e.g. eye dryness, first bite pain) and warranted care recommendations. In only two cases did the patient require further in-person procedural (hematoma evacuation, seroma aspiration) follow-ups. For the other 91.7% of visits (n = 88), no additional recommendations were required as patients experienced uncomplicated postoperative courses. Of all the patients, 26.1% (n = 23) were instructed to follow-up for routine surveillance. All other patients, 73.9% (n = 65) were instructed to follow-up as needed. Conclusion Postoperative parotidectomy evaluation is highly amenable to being performed by video. A telemedicine option offers convenience for patients in the majority of cases without compromising clinical assessment and judgment for the physician.