US Academic Centers Research Articles

Needlestick injuries among anesthesia providers from a large US academic center: A 10-year retrospective analysis

Study objectiveAnesthesiologists are at high risk for needlestick injury. Such injuries pose a serious health threat from exposure to bloodborne pathogens. This retrospective analysis aimed to examine needlestick injury rate among anesthesia providers between 2010 and 2020 at the University of California Los Angeles, Department of Anesthesiology and Perioperative Medicine to determine specialty-specific factors associated with these injuries. DesignRetrospective analysis. SettingAcademic Anesthesiology Department. Patients and interventionsNone. MeasurementsAll reported incidents of needlestick injuries to employees are sent to the Injury and Illness Prevention Committee. We included all anesthesia residents, fellows, nurse anesthetists, solo anesthesiologists, and supervising anesthesiologists. Main resultsThe overall rate of reported needlestick injuries was 5.3%. The rates for anesthesia residents were 2.1%, 13.5%, 7.9%, and 6.7% for post graduate year 1–4 (PGY 1–4) residents. The rates were 14.3%, 4.7%, 2.1%, and 6.9% for fellows, nurse anesthetists, supervising anesthesiologists, and solo anesthesiologists, respectively. We found that PGY2 residents had a higher injury rate than PGY1 residents (p-value<0.001). When grouping PGY2, PGY3, and PGY4 residents together, they had a collective rate of 9.4%. Furthermore, residents had a higher needlestick injury rate than supervising anesthesiologists (p-value <0.001). ConclusionsPGY2 residents and fellows had the highest rate of needlestick injury. Our study highlights the trend of increasing sharps injuries after PGY1 while supervising anesthesiologists had the lowest rate. Proposed mechanisms for the increased sharps injuries include residents' transition from medicine-based internship to the operating room environment with increased exposure to potentially injurious equipment, overnight call, and increased work-related and cognitive stress. Improving understanding of institution-specific prevention programs, raising awareness during their initial high-intensity training period with one-to-one supervision when habits are formed, and reducing exposure to sharps using a needleless system are some steps toward reducing the incidence of sharps injuries in a field where the risk remains high.

Nonmelanoma Skin Cancer in Patients Older Than Age 85 Years Presenting for Mohs Surgery

It has been suggested that Mohs surgery for skin cancer among individuals with limited life expectancy may be associated with needless risk and discomfort, along with increased health care costs. To investigate patient- and tumor-specific indications considered by clinicians for treatment of nonmelanoma skin cancer in older individuals. This multicenter, prospective cohort study was conducted using data from US private practice and academic centers. Included patients were those older than age 85 years presenting for skin cancer surgery and referred for Mohs surgery, with reference groups of those younger than age 85 years receiving Mohs surgery and those older than age 85 years not receiving Mohs surgery. Data were analyzed from November 2018 through January 2019. Mohs surgery for nonmelanoma skin cancer. Reason for treatment selection. Among 1181 patients older than age 85 years referred for Mohs surgery (724 [61.9%] men among 1169 patients with sex data; 681 individuals aged >85 to 88 years [57.9%] among 1176 patients with age data) treated at 22 sites, 1078 patients (91.3%) were treated by Mohs surgery, and 103 patients (8.7%) received alternate treatment. Patients receiving Mohs surgery were more likely to have tumors on the face (738 patients [68.5%] vs 26 patients [25.2%]; P < .001) and nearly 4-fold more likely to have high functional status (614 patients [57.0%] vs 16 patients [15.5%]; P < .001). Of 15 distinct reasons provided by surgeons for opting to proceed with Mohs surgery, the most common were patient desire for treatment with a high cure rate (712 patients [66.0%]), good or excellent patient functional status for age (614 patients [57.0%]), and high risk associated with the tumor based on histology (433 patients [40.2%]). This study found that older patients who received Mohs surgery often had high functional status, high-risk tumors, and tumors located on the face. These findings suggest that timely surgical treatment may be appropriate in older patients given that their tumors may be aggressive, painful, disfiguring, and anxiety provoking.

Severity of Cytokine Release Syndrome Influences Outcome After Axicabtagene Ciloleucel for Large B cell Lymphoma: Results from the US Lymphoma CAR-T Consortium

BackgroundThe majority of patients with large B-cell lymphoma treated with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, develop cytokine release syndrome (CRS). Whether the lack of development of CRS with axi-cel is associated with inferior lymphoma outcomes is unknown. Additionally, relationship between CRS grade and lymphoma outcome is not well established. MethodsThe US Lymphoma CAR T Consortium includes seventeen US academic centers that contribute data independently of manufacturers. We analyzed the modified intent-to-treat population of 275 patients receiving axi-cel in two different ways: 1) Two group analysis comparing no CRS with any grade CRS; 2) Three group analysis comparing grade 0 CRS with grade 1 to 2 CRS, and grade 3-5 CRS. ResultsIn this large multi-center observational cohort of 275 patients receiving axi-cel, 9% (n = 24) did not develop CRS, 84% (n = 232) developed grade 1-2 CRS, and 7% (n = 19) developed grade 3 to 5 CRS. Patients without CRS, compared with those having any grade CRS, had similar overall response rates (ORR), lower complete response (CR) rates and inferior progression free survival (PFS) with no statistically significant difference in overall survival (OS). Patients experiencing grade 1 to 2 CRS had superior CR rate and PFS, as compared to those without CRS or with grade 3 to 5 CRS. Grade 3 to 5 CRS was associated with a worse OS. ConclusionOverall, durable responses were seen in patients that did not develop CRS, however grade 1 to 2 CRS was associated with better outcomes while those with grade 3 to 5 experienced the worse outcomes.

COVID-19 vaccines in pregnancy.

COVID-19 caused by SARS-CoV-2 coronavirus has been associated with severe illness in pregnant women. Furthermore, COVID-19 during pregnancy is associated with adverse fetal outcomes including preterm labor. Pregnant women were largely excluded from initial clinical trials investigating the safety and efficacy of COVID-19 vaccines; however, they have since been included as part of the routine roll-out of these vaccines. This narrative review synthesizes the evidence on the safety, immunogenicity, and effectiveness predominantly of the mRNA COVID-19 vaccines which have been most widely used in pregnant women.

COVID-19 Vaccine Hesitancy during the Perinatal Period: Understanding Psychological and Cultural Factors to Improve Care and Address Racial/Ethnic Health Inequities.

COVID-19 Vaccine Hesitancy during the Perinatal Period: Understanding Psychological and Cultural Factors to Improve Care and Address Racial/Ethnic Health Inequities.

Perioperative use of glucose containing solutions in infants less than 6months of age: A clinical practice survey among US academic centers.

Although there is a wide breadth of literature on glucose homeostasis in infants, standardization of perioperative hypoglycemia diagnosis and management is lacking. Survey of academic pediatric anesthesiology departments across the USA to evaluate institutional policies regarding the perioperative use of glucose containing solutions in infants less than 6months of age. A questionnaire was sent to 20 United States university affiliated academic pediatric anesthesiology departments. The responses suggest that, in the centers surveyed, glucose administration in infants is largely practitioner dependent. Two respondents (10%) claim to have a departmental policy regarding glucose administration in infants less than 6months of age. In premature infants, 75% of respondents administer glucose. When administering glucose, 75% of physicians surveyed replete infants at their maintenance intravenous fluid rate. There was discrepancy among practitioners regarding initiation of hypoglycemia treatment, 35% treat infants at a blood glucose level of 70mg/dl, 30% at BG 60mg/dl, 25% at 50mg/dl, and 10% are unsure. This survey highlights the lack of consensus, at least among pediatric anesthesiologists working in US academic centers, regarding blood glucose management in infants less than 6months of age. There is a need to define the indications for using glucose containing solutions in infants during the perioperative period, their ideal content, the appropriate thresholds for hypo- and hyperglycemia as well as the optimal point-of care glucose monitoring intervals.

A Mixed-methods Assessment of the Impact of Insurance Issues on the Emotional and Physical Health of Patients With Inflammatory Bowel Disease.

In patients with inflammatory bowel disease (IBD), failure to adhere to treatment regimens due to insurance issues can lead to disease complications. Our aim was to examine patients' perceptions of the impact of insurance issues on their health. Twenty-nine patients with IBD at a large US academic center and an insurance issue participated in a mixed-methods study. Retrospective chart review and an online questionnaire were completed to collect demographic information, IBD characteristics, and validated resilience scores. Semistructured interviews were completed for insurance experiences, which were coded independently by 2 coders for themes. Twenty-nine patients completed the interview, and 24 completed the online survey. Sixteen had Crohn's disease, 13 had ulcerative colitis, and 66% were female. The most common insurance issue was lapsed insurance. Many experienced physical consequences, with 58% having flares, 14% undergoing surgery, and 14% developing antibodies. All emotional responses were negative, with the majority feeling stressed (38%). Providers were uninformed of insurance issues in 28% of cases. When asked about perceived resilience, 41% felt incapable of managing the situation, and 45% gave up trying to solve the problem. When asked how to improve going forward, 38% requested an easily accessible advocate to guide them. A large proportion of our cohort chose not to inform their provider, felt incapable of managing on their own, and gave up on resolving their insurance issue. This highlights the need to consider restructuring the insurance system, to identify those at risk for insurance issues, and to make advocates available to avoid devastating consequences.

Objective disease activity assessment and therapeutic drug monitoring prior to biologic therapy changes in routine inflammatory bowel disease clinical practice: TARGET-IBD

BackgroundInflammatory bowel disease (IBD) treatment paradigms recommend objective disease activity assessment and reactive therapeutic drug monitoring (TDM) prior to changes in biologic therapy. We aimed to describe objective marker and TDM assessment in routine clinical practice prior to biologic therapeutic changes in adult IBD patients.MethodsTARGET-IBD is a prospective longitudinal cohort of over 2100 IBD patients receiving usual care at 34 US academic or community centers enrolled between June 2017 and October 2019 who received biologic therapy and had a dose change or biologic discontinuation for lack of efficacy. Objective markers of disease activity within 12 weeks prior included fecal calprotectin, C-reactive protein (CRP), endoscopy, computed tomography (CT) and magnetic resonance imaging (MRI). TDM data for infliximab or adalimumab was obtained.Results525 patients (71.4% Crohn’s disease [CD], 28.6% ulcerative colitis [UC]) receiving biologic therapy underwent dose change (55.6%) or discontinuation (44.4%) for lack of efficacy. The majority were Caucasian (85.7%), 18–39 years old (52.2%), privately insured (81.5%), and at academic centers (73.7%). For dose changes, 67.5% had at least one objective disease activity assessment or TDM in the 12 weeks prior (CD 67.9%, UC 66.2%; P = 0.79). The most common objective marker was CRP in both CD (39.1%) and UC (54.5%). CRP and calprotectin were used significantly more in UC (P = 0.02 and P = 0.03). TDM was obtained in 30.7% (28.8% UC, 31.4% CD; P = 0.72) prior to dose change. For biologic discontinuation, 79.4% patients underwent objective assessment or TDM prior. In CD, CRP (46.3%) was most common, and CT (P = 0.03) and MRI (P < 0.001) were significantly more frequent than in UC. TDM was performed in 40.1% of patients (43.5% UC, 38.0% CD, P = 0.49) prior to discontinuation. Among all participants with dose change or discontinuation, endoscopy was performed in 29.3% with CD and 31.3% with UC. Academic care setting was associated with objective assessment before therapy change (OR 1.59, 95% CI 1.01–2.50).ConclusionNearly one-third of patients undergoing a biologic dose change or discontinuation do not undergo objective disease activity assessment or TDM. Assessment choice differs by disease. Future studies assessing the impact of such practices on long-term outcomes are needed.

Abstract 157: Ischemic Strokes In Patients With Atrial Fibrillation On Oral Anticoagulant: The Neuro-AFib Study

Background: Ischemic stroke (IS) admissions in patients with atrial fibrillation (AF) using either direct oral anticoagulants (DOAC) or Vitamin K antagonists (VKA) are commonly seen in stroke units but data on their prevalence and causes are scarce. Understanding the frequency/causes of failures of current FDA-approved preventive methods in patients with AF is important to reduce stroke risk and related death/disability. Methods: The Neuro-AFib study is a multicenter effort geared toward elucidating the causes and consequences of IS and hemorrhagic stroke in a contemporary AF cohort. Detailed clinical, laboratory and multimodal neuro- and cardiac imaging data from known AF patients consecutively admitted to 22 US academic stroke centers with an IS between 1/2018-12/2019 were used to compare characteristics of IS on vs off oral anticoagulants. Results: Out of 6443 IS patients with AF, 4898 (76%) had known AF prior to the acute stroke. Among these patients with known AF, 2204 (45%) were using oral anticoagulants [OAC= DOAC (59.3%) or VKA (40.7%)]. Patients who had IS on OAC were younger (76.8 + 11 vs 78 + 12, p=0.001), had higher mean CHA 2 DS 2 -VASc scores (4.17 + 1.5 vs 3.9 + 1.5, p&lt;0.0001), and more likely to have a past history of IS/TIA when compared to non-OAC group (35% vs 23%, p&lt;0.0001). In a multivariable logistic regression model, history of IS/TIA, diabetes, hyperlipidemia, heart failure, prosthetic heart valve, sleep apnea, permanent atrial fibrillation, left atrial dilation and ischemic arterial disease were all independently associated with IS on OAC (all p&lt;0.05). Imaging data were complete in 15% of the cohort and IS on OAC group had more acute lacunar infarcts, and extracranial and intracranial atherosclerotic disease causing 50% or more ipsilateral stenosis compared to patients with IS off OAC (all p&lt;0.05). Conclusions: Based on a large multicenter contemporary cohort of IS patients with known AF, the numbers of patients who failed OACs (and especially DOACs) are high. These patients have severe vascular risk factor loads, concurrent etiologies, and they are more likely to have recurrent ischemic events. Further detailed data focused on imaging and IS mechanisms from this contemporary cohort will be ready to be presented during ISC 2022.

Feasibility and utility of synthetic control arms derived from real-world data to support clinical development.

528 Background: ‘Synthetic’ control arms (SCAs), created using electronic health records (EHRs), have immense potential to augment clinical trial findings and provide a rich context of real-world evidence (RWE) while reducing patient (pt) and sponsor burden (Gottlieb 2019). PICI0002 (PRINCE) is a ph1b/2 study evaluating APX005M with gemcitabine (gem) and nab-paclitaxel (NP) ± nivolumab for the treatment of metastatic pancreatic adenocarcinoma (mPDAC; NCT03214250). PRINCE pts were enrolled from select US academic cancer centers and a global, ph3 study was utilized for an historical reference control (Von Hoff 2013). To address the perceived limitations of this design, we explored the feasibility and utility of developing a contemporary SCA using real-world data (RWD). Methods: The SCA was derived using retrospective pt data from the two highest enrolling participating centers on PRINCE. Pts meeting key PRINCE eligibility criteria, who received gem/NP in the two years preceding the trial start date, were identified using an electronic phenotyping algorithm applied to cancer registry and EHR data, followed by manual review. Baseline characteristics, treatment exposure, efficacy and survival data were extracted electronically and via manual chart abstraction. Data were stored in a REDCap database built and housed by the Parker Institute for Cancer Immunotherapy. SCA pt characteristics were compared with PRINCE and overall survival (OS; time from initiation of gem/NP to death) was compared to historical reference controls (Table). Results: N=68 pts treated with gem/NP meeting PRINCE eligibility criteria were identified. All pts were deceased at the time of analysis. SCA pts had comparable baseline characteristics to PRINCE pts; key differences included inferior performance status and a higher proportion of pts presenting with a de novo mPDAC diagnosis. Median time on gem/NP was 4.8 months (mos; range 0-39). Median OS was 11.5 mos (95% CI 9.0-13.6) and 1-year OS was 43% (95% CI 31-55), in line with historical controls (Table). Conclusions: This study confirms the feasibility and utility of generating a control arm via a semi-automated approach. Current limitations entail manual oversight requirements as well as the known constraints of RWD, including associated biases and lack of available RECIST data. These limitations stand to evolve alongside EHR technologies. SCAs using RWD may help inform the value of prospective data by providing a contemporary reference of RWE. In some circumstances, SCAs may also serve as an alternative to traditional control arms, particularly for well-characterized standard therapies.[Table: see text]

Abstract WMP101: Potential Causes Of Anticoagulant Underuse In Patients With Atrial Fibrillation Presenting With Ischemic Strokes

Background: Underuse of FDA-approved stroke prevention methods in atrial fibrillation (AF) remains a major problem. We aimed to explore the potential causes of oral anticoagulant (OAC) non-use and compare the frequency of these factors between AF patients with acute ischemic stroke (AIS) off and on oral anticoagulant (OAC). Methods: The Neuro-AFib study is a multicenter observational study aiming to clarify the causes of different stroke types in a contemporary AF cohort. Potential causes of OAC non-use were systematically collected from all enrolled patients based on the exclusion criteria of the Direct OAC (DOAC) studies. The frequency of potential causes of OAC non-use (AIS-off-OAC) are explored in AF patients consecutively admitted to 22 US academic stroke centers with an AIS between 1/2018-12/2019, and these rates are compared to AIS-on-OAC. Results: Among 4898 patients with known AF who had IS, 2694 (55%) were not using any OAC, and 45% were AIS-on-OAC. CHA2DS2-VASc &lt;2, the cutoff representing low embolic risk until late 2019, was found in 7% of AIS-off-OAC group compared to 3.8% in AIS-on-OAC (p&lt;0.0001). The most common factor in OAC non-use group was history of falls (26%) vs 18% in AIS-on-OAC group (p=0.004). History of bleeding [intracranial (2.3%) and extracranial (18.5%)] was found in 20.8% of AIS-off-OAC vs 10.4% of AIS-on-OAC group (p&lt;0.0001). 82.6% of these hemorrhages were classified as major bleeds. Pre-stroke cognitive impairment was also common in AIS-off-OAC (21.7%). Renal failure (creatinine &gt;2mg/dl) was found in 13% of AIS-off-OAC. Gait problems leading to limited mobility (10%) and excessive alcohol use (3.8%) were other potential factors for OAC non-use. Among OAC non-users, 64% had at least one risk factor defined above. Conclusions: In a large multicenter contemporary IS cohort with known AF, 55% of patients were not on OAC, and about two thirds of them had a reason that would exclude them from the phase 3 DOAC studies. Other than improving the accuracy of risk prediction algorithms, research should focus on identifying optimal management approaches for this large AF population who present challenges to lifelong OAC use. FDA-approved left atrial appendage closure procedures can be considered in such AF patients.

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018

Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity. To review survival, in-hospital morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months' corrected age for extremely preterm infants. Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months' corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age. Extremely preterm birth. Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months' corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices. The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment. Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks' gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.

Practice Patterns Pre-CART for Aggressive B-Cell Lymphomas: Patient Selection and Real World Salvage and Bridging Practices

Practice Patterns Pre-CART for Aggressive B-Cell Lymphomas: Patient Selection and Real World Salvage and Bridging Practices

Long-Term Outcomes of Patients with Large B-Cell Lymphoma Treated with Standard-of-Care Axicabtagene Ciloleucel: Results from the US Lymphoma CAR-T Cell Consortium

Long-Term Outcomes of Patients with Large B-Cell Lymphoma Treated with Standard-of-Care Axicabtagene Ciloleucel: Results from the US Lymphoma CAR-T Cell Consortium

A Multi-Institutional Retrospective Analysis of T-Cell Lymphomas with Central Nervous System Relapse

A Multi-Institutional Retrospective Analysis of T-Cell Lymphomas with Central Nervous System Relapse

Use of Red Blood Cell Phenotypes for Second Line Therapy Selection in Sickle Cell Disease

INTRODUCTIONIn sickle cell disease (SCD), abnormal red blood cells (RBCs) sickle upon deoxygenation due to polymerization of hemoglobin S (HbS). Sickle RBCs exhibit poor deformability and increased viscosity, density, and microvascular adhesion. These rheological properties can be measured using existing devices. An oxygen-gradient ektacytometer measures the deformability of sickle RBCs under normoxic (maximum elongation index, or EImax) and hypoxic conditions (minimum elongation index, or EImin), and the pO 2 level at which sickling beings (point of sickling, or PoS). Dense RBCs are measured using a commercially available hematology analyzer. The hematocrit-to-viscosity ratio (HVR), an oxygen delivery index, is calculated based on the viscosity as measured by a cone and plate viscometer. RBC adhesion in the microvasculature can be modeled using a laminin-lined microfluidics device.These rheological biomarkers correlate with clinical complications such as pain events and acute chest syndrome, and are modified by known, clinically effective therapies such as hydroxyurea (HU) and transfusion (TF). HU is the standard of care for most individuals with SCD and positively modifies EImin, EImax, PoS, HVR, adhesion, and %DRBC. Recently, new agents to treat SCD have emerged including voxelotor, crizanlizumab, and pyruvate kinase activators like etavopivat, which have more targeted effects. It is essential to pair the appropriate novel agent to the patient, addressing their most prominent RBC abnormality remaining after HU therapy.We hypothesize that there is significant variability of rheology biomarkers between individuals with SCD on standard of care therapy, and that the most severe aspects of their RBC pathophysiology can be identified and targeted by novel second line therapies for clinical optimization.METHODSWe collected peripheral blood in EDTA under an IRB approved protocol from 312 pediatric patients with SCD ranging in age from 2 to 21 years, 70% on HU. Subjects on chronic TF therapy were excluded. We measured whole blood viscosity at 45s -1 shear and calculated the HVR. %DRBC and complete blood counts were obtained using an ADVIA hematology analyzer (Siemens) and EImin, EImax, and PoS obtained using oxygen gradient ektacytometry (Lorrca, RR Mechatronics). RBCs from 17 HbSS subjects were analyzed for adhesion index to a laminin-lined microfluidics device. Values were assembled for each biomarker into histograms to demonstrate distribution, and quartile ranked. Venn diagrams were constructed comparing overlap between top 25% most severe rheology biomarkers to demonstrate effectiveness of a targeted, precision medicine approach to adding second line therapies to individuals with SCD.RESULTSDistribution of biomarkers in a typical pediatric SCD population in a US academic center are shown in Figure 1. High PoS, adhesion index, %DRBC, and low EImin and EImax, low HVR, are associated with disease severity and clinical complications in SCD; biomarker values were stratified from high to low severity association. The most severe quartile subjects from each biomarker were compared, and percentage of overlap noted (Figure 2).CONCLUSIONOur rheologic assessment of a large pediatric cohort heavily treated with HU indicates a broad distribution of RBC phenotypes. Even on HU, patients exhibited loss of deformability, sickling, adhesion, or RBC density abnormalities, with little overlap of unrelated biomarkers associated with disease severity in an individual, i.e. the individuals with very high PoS did not have low HVR (16% of highest severity quartile subjects in common), compared to related biomarkers PoS and EImin or EImax (48% of highest severity quartile subjects in common). Only four subjects, all on HU, were in the quartile associated with highest severity for all biomarkers. Given the lack of overlapping pathology between different red cell abnormalities, selection of the appropriate agent should be straightforward. With three new FDA approved therapies for SCD and novel therapies in clinical trials, it is possible to choose the appropriate second agent to be added to HU based on individual patient RBC phenotype according to the principles of precision medicine. Future goals include CLIA certification for novel devices like the oxygen gradient ektacytometer and adhesive microfluidics at major academic SCD centers and use of these biomarkers in routine patient care. [Display omitted] DisclosuresRab: Agios Pharmaceuticals: Research Funding; Axcella Health: Research Funding. Lam: Sanguina, Inc.: Current holder of individual stocks in a privately-held company. Wijk: Agios Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Axcella health: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Sheehan: Beam Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Novartis: Research Funding.

S1001 Outcomes of Duodenal Stent Placement for Malignant Gastric Outlet Obstruction. Experience for a Large Tertiary Care Center

Introduction: Endoscopic duodenal stent (DS) placement is a recognized treatment for the palliation of malignant gastric outlet obstruction (GOO). While highly effective and safe, the durability of palliation has been in question due to delayed adverse events. This study aimed to evaluate the clinical outcomes of duodenal stent placement in a large academic cancer center. Methods: This is a single-center retrospective study. Data were collected from all patients who underwent DS placement between January 2012 and August 2020. The primary endpoint was clinical success, defined as oral intake 1-week after DS placement (Gastric Outlet Obstruction Scoring System, GOOSS >1). Secondary endpoints were stent occlusion, need for re-interventions, and adverse events. Results: A total of 223 patients were included; 112 (51%) were female and 144 (64%) White. The median age was 63 (IQR 56-70). The etiologies for malignant GOO were: pancreatic cancer 98 (44%), gastric cancer 35 (15.7%), cholangiocarcinoma 21 (9.4%), colorectal cancer 13 (5.8%), and others. The most common site of obstruction was the duodenum, proximal to the major papilla 106 (48%), and the majority of patients were unable to tolerate PO intake (GOOSS=0) 169 (78%) prior to DS placement. After DS placement, 185 (88%) patients were started on a diet within one-week (GOOSS >1), p < .05. Two patients had minor intraprocedural complications, and 114 (51.1%) patients reported delayed adverse events, the most common being stent occlusion due to tissue ingrowth in 52 (23.3%). In this group, the median duration of stent patency was 51 days (IQR 13-196) (Figure 1). Endoscopic revisions were required in 84 (38%) patients, and a new stent was placed in the first revision in 49 patients (22%). Neither etiology nor location of stenosis was found to be a statistically significant predictor of clinical success or stent patency. Median survival after DS placement was 90 days (IQR 38-193). Conclusion: The results of this long-term study of DS placement at a major US academic cancer center demonstrate its continued safety and efficacy for the short-term palliation of malignant GOO. However, stent failure requiring repeat intervention limits the long-term effectiveness of duodenal stents, and therefore alternative approaches should be considered for patients who require long-term palliation of malignant GOO.

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions

AbstractProphylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic

Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed. To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19. This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021. The presence of a COVID-19 diagnosis using ICD-10. Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using t test, and categorical variables were analyzed using χ2. Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non-COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%]; P = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%]; P < .001). Women giving birth with COVID-19, compared with women without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; odds ratio [OR], 5.84 [95% CI, 5.46-6.25]; P < .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42]; P < .001), and in-hospital mortality (24 women [0.1%] vs 71 [<0.01%]; OR, 15.38 [95% CI, 9.68-24.43]; P < .001). This retrospective cohort study found that women with COVID-19 giving birth had higher rates of mortality, intubation, ICU admission, and preterm birth than women without COVID-19.

Multi‐center analysis of practice patterns and outcomes of younger and older patients with mantle cell lymphoma in the rituximab era

Clinical outcomes and predictors of survival in patients with newly diagnosed mantle cell lymphoma (MCL) treated in the rituximab era (2000-2015) at 12 US academic centers were assessed to identify determinants of survival across age groups. Objectives were to characterize and compare practice patterns, outcomes and prognostic factors for survival in younger patients (age < 65) and older patients (age ≥ 65 years). Among 1162 patients included, 697 were younger and 465 were older. In younger patients, 2-year progression free survival (PFS) and overall survival (OS) rates were 79% and 92% respectively; blastoid histology, ECOG ≥ 2, and lack of maintenance rituximab (MR) remained statistically relevant to poor OS on univariate analysis (UVA) and multivariate analysis (MVA). In older patients, 2-year PFS and OS rates were 67% and 86% respectively; lack of maintenance rituximab remained significantly associated with inferior PFS and OS on UVA and MVA (p< 0.001). Two-year PFS rates were 79%, and 67% and 2-year OS rates were 92% and 86% for ages < 65 and ≥ 65 respectively (p< 0.001). First-line high-dose cytarabine exposure and/or MR lessened the negative impact of age on survival. Taken collectively, survival outcomes for older patients remain inferior to those of younger patients in the rituximab era. However, maintenance rituximab and potentially high-dose cytarabine-based induction can mitigate the negative impact of age on survival.