Brain-state mediated modulation of inter-laminar dependencies in visual cortex.

Spatial attention is critical for recognizing behaviorally relevant objects in a cluttered environment. How the deployment of spatial attention aids the hierarchical computations of object recognition remains unclear. We investigated this in the laminar cortical network of visual area V4, an area strongly modulated by attention. We found that deployment of attention strengthened unique dependencies in neural activity across cortical layers. On the other hand, shared dependencies were reduced within the excitatory population of a layer. Surprisingly, attention strengthened unique dependencies within a laminar population. Crucially, these modulation patterns were also observed during successful behavioral outcomes that are thought to be mediated by internal brain state fluctuations. Successful behavioral outcomes were also associated with phases of reduced neural excitability, suggesting a mechanism for enhanced information transfer during optimal states. Our results suggest common computation goals of optimal sensory states that are attained by either task demands or internal fluctuations.

Practice efficiency and total cost of care with bispecifics and CAR-T in relapsed/refractory diffuse large B-cell lymphoma: an institutional perspective1.

Aim: Novel treatment options for relapsed/refractory diffuse large B-cell lymphoma include T-cell targeting therapies. Practice efficiency and cost are important for informed treatment decisions. Materials/methods: An institutional decision-maker cost model was developed for 6-month, 1-year and median cycles of treatment time horizons comparing practice efficiency and costs of epcoritamab vs glofitamab and axicabtagene ciloleucel (axi-cel). Results: Overall, epcoritamab required the shortest personnel and chair time, except over 1 year (second shortest chair time). Across all time horizons, epcoritamab was cost-saving vs axi-cel and had similar costs to glofitamab on a per-month basis. Conclusion: Epcoritamab reduced personnel and chair time. Additionally, epcoritamab was cost-saving vs axi-cel and had similar costs to glofitamab on a per-month basis.

There are new ways to treat diffuse large B-cell lymphoma, which is a type of cancer called lymphoma. When new treatments are available it is important to see if they take more or less time to give to patients and how much they cost versus other treatments. This study looked at three drugs used to treat diffuse large B-cell lymphoma, including epcoritamab, axi-cel and glofitamab. It estimated the time and cost with those treatments in patients who get them for 6 months, 1 year or for the most common length of time in the clinical trials. In most of the scenarios, epcoritamab had the least time needed for nurses or doctors and the least time needed for a patient to be in a chair in a clinic. When thinking about the cost per month, epcoritamab saved money versus axi-cel and was similar to glofitamab.

Automated 3D analysis of social head-gaze behaviors in freely moving marmosets.

Social communication relies on the ability to perceive and interpret the direction of others' attention, which is commonly conveyed through head orientation and gaze direction in both humans and non-human primates. However, traditional social gaze experiments in non-human primates require restraining head movements, which significantly limit their natural behavioral repertoire. Here, we developed a novel framework for accurately tracking facial features and three-dimensional head gaze orientations of multiple freely moving common marmosets (Callithrix jacchus). To accurately track the facial features of marmoset dyads in an arena, we adapted computer vision tools using deep learning networks combined with triangulation algorithms applied to the detected facial features to generate dynamic geometric facial frames in 3D space, overcoming common occlusion challenges. Furthermore, we constructed a virtual cone, oriented perpendicular to the facial frame, to model the head gaze directions. Using this framework, we were able to detect different types of interactive social gaze events, including partner-directed gaze and jointly-directed gaze to a shared spatial location. We observed clear effects of sex and familiarity on both interpersonal distance and gaze dynamics in marmoset dyads. Unfamiliar pairs exhibited more stereotyped patterns of arena occupancy, more sustained levels of social gaze across inter-animal distance, and increased gaze monitoring. On the other hand, familiar pairs exhibited higher levels of joint gazes. Moreover, males displayed significantly elevated levels of gazes toward females' faces and the surrounding regions irrespective of familiarity. Our study lays the groundwork for a rigorous quantification of primate behaviors in naturalistic settings.

Development of a Marmoset Apparatus for Automated Pulling (MarmoAAP) to Study Cooperative Behaviors.

In recent years, the field of neuroscience has increasingly recognized the importance of studying animal behaviors in naturalistic environments to gain deeper insights into ethologically relevant behavioral processes and neural mechanisms. The common marmoset (Callithrix jacchus), due to its small size, prosocial nature, and genetic proximity to humans, has emerged as a pivotal model toward this effort. However, traditional research methodologies often fail to fully capture the nuances of marmoset social interactions and cooperative behaviors. To address this critical gap, we developed the Marmoset Apparatus for Automated Pulling (MarmoAAP), a novel behavioral apparatus designed for studying cooperative behaviors in common marmosets. MarmoAAP addresses the limitations of traditional behavioral research methods by enabling high-throughput, detailed behavior outputs that can be integrated with video and audio recordings, allowing for more nuanced and comprehensive analyses even in a naturalistic setting. We also highlight the flexibility of MarmoAAP in task parameter manipulation which accommodates a wide range of behaviors and individual animal capabilities. Furthermore, MarmoAAP provides a platform to perform investigations of neural activity underlying naturalistic social behaviors. MarmoAAP is a versatile and robust tool for advancing our understanding of primate behavior and related cognitive processes. This new apparatus bridges the gap between ethologically relevant animal behavior studies and neural investigations, paving the way for future research in cognitive and social neuroscience using marmosets as a model organism.

Brain-state mediated modulation of inter-laminar dependencies in visual cortex.

Spatial attention is a quintessential example of adaptive information processing in the brain and is critical for recognizing behaviorally relevant objects in a cluttered environment. Object recognition is mediated by neural encoding along the ventral visual hierarchy. How the deployment of spatial attention aids these hierarchical computations is unclear. Prior studies point to two distinct mechanisms: an improvement in the efficacy of information directed from one encoding stage to another, and/or a suppression of shared information within encoding stages. To test these proposals, it is crucial to estimate the attentional modulation of unique information flow across and shared information within the encoding stages of the visual hierarchy. We investigated this in the multi-stage laminar network of visual area V4, an area strongly modulated by attention. Using network-based dependency estimation from multivariate data, we quantified the modulation of inter-layer information flow during a change detection task and found that deployment of attention indeed strengthened unique dependencies between the input and superficial layers. Using the partial information decomposition framework, we estimated the modulation of shared dependencies and found that they are reduced specifically in the putative excitatory subpopulations within a layer. Surprisingly, we found a strengthening of unique dependencies within the laminar populations, a finding not previously predicted. Crucially, these modulation patterns were also observed during successful behavioral outcomes (hits) that are thought to be mediated by endogenous brain state fluctuations, and not by experimentally imposed attentive states. Finally, phases of endogenous fluctuations that were optimal for 'hits' were associated with reduced neural excitability. A reduction in neural excitability, potentially mediated by diminished shared inputs, suggests a novel mechanism for enhancing unique information transmission during optimal states. By decomposing the modulation of multivariate information, and combined with prior theoretical work, our results suggest common computations of optimal sensory states that are attained by either task demands or endogenous fluctuations.

Laminar compartmentalization of attention modulation in area V4 aligns with the demands of visual processing hierarchy in the cortex.

Attention selectively enhances neural responses to low contrast stimuli in visual area V4, a critical hub that sends projections both up and down the visual hierarchy. Veridical encoding of contrast information is a key computation in early visual areas, while later stages encoding higher level features benefit from improved sensitivity to low contrast. How area V4 meets these distinct information processing demands in the attentive state is unknown. We found that attentional modulation in V4 is cortical layer and cell-class specific. Putative excitatory neurons in the superficial layers show enhanced boosting of low contrast information, while those of deep layers exhibit contrast-independent scaling. Computational modeling suggested the extent of spatial integration of inhibitory neurons as the mechanism behind such laminar differences. Considering that superficial neurons are known to project to higher areas and deep layers to early visual areas, our findings suggest that the interactions between attention and contrast in V4 are compartmentalized, in alignment with the demands of the visual processing hierarchy.

Sex disparities in treatment patterns after metformin initiation among patients with type 2 diabetes mellitus.

PURPOSE: To assess sex differences in treatment patterns after metformin initiation among type 2 diabetes mellitus (T2D) patients. METHODS: A cohort study was conducted using the Groningen Initiative to ANalyze Type 2 diabetes Treatment (GIANTT) primary care database. Patients aged ≥18 years initiating metformin were followed 2-5 years. Markov modeling was conducted to estimate treatment transition rates and calculate adjusted hazard ratios (aHR) with 95% confidence intervals (CI) comparing men with women adjusted for age, HbA1c level at initiation, and cardiovascular disease history. Kaplan-Meier analyses and Cox proportional-hazards models were used to determine the time to and likelihood of getting treatment intensification. HbA1c levels at initiation and intensification were compared using Mann-Whitney U tests. RESULTS: In total, 11 508 metformin initiators were included (50.1% women). The most common transition after initiation was a dose increase (probability women 0.52, men 0.59, no significant difference). Women were more likely than men to switch to any other non-insulin hypoglycemic agent after initiation (aHR 1.66; 95% CI 1.31-2.12), after dose increase (aHR 1.48; 95% CI 1.10-1.98) and after dose decrease (aHR 2.64; 95% CI 1.28-5.46). Time to intensification was longer, time to switching was shorter, and HbA1c levels at initiation and intensification were lower for women than men. CONCLUSIONS: Sex disparities were observed in treatment transitions after metformin initiation. Women more often switched treatment than men, which suggest that prescribers acknowledge more tolerance or other problems for metformin in women. Men intensified treatment earlier and at higher HbA1c levels, indicative of a higher need for treatment intensification.

Laminar mechanisms of saccadic suppression in primate visual cortex.

Saccadic eye movements are known to cause saccadic suppression, a temporary reduction in visual sensitivity and visual cortical firing rates. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within visual area V4. We find subpopulation-specific differences in the magnitude and timing of peri-saccadic modulation. Input-layer neurons show changes in firing rate and inter-neuronal correlations prior to saccade onset, and putative inhibitory interneurons in the input layer elevate their firing rate during saccades. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input-layer-targeting pathway can initiate saccadic suppression by enhancing local inhibitory activity. Collectively, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.

The orbitofrontal cortex: A goal-directed cognitive map framework for social and non-social behaviors.

The orbitofrontal cortex (OFC) is regarded as one of the core brain areas in a variety of value-based behaviors. Over the past two decades, tremendous knowledge about the OFC function was gained from studying the behaviors of single subjects. As a result, our previous understanding of the OFC's function of encoding decision variables, such as the value and identity of choices, has evolved to the idea that the OFC encodes a more complex representation of the task space as a cognitive map. Accumulating evidence also indicates that the OFC importantly contributes to behaviors in social contexts, especially those involved in cooperative interactions. However, it remains elusive how exactly OFC neurons contribute to social functions and how non-social and social behaviors are related to one another in the computations performed by OFC neurons. In this review, we aim to provide an integrated view of the OFC function across both social and non-social behavioral contexts. We propose that seemingly complex functions of the OFC may be explained by its role in providing a goal-directed cognitive map to guide a wide array of adaptive reward-based behaviors in both social and non-social domains.

COVID-19 Breakthrough Infections among Patients Aged ≥65 Years in Serbia: Morbidity and Mortality Overview.

BACKGROUND: Vaccines against severe acute respiratory syndrome coronavirus 2 have shown effectiveness in the prevention of COVID-19. Breakthrough infections occur, and age has been shown to be one of the dominant risk factors for poorer outcome. This research focuses on characteristics of breakthrough infections in older adults. METHODS: This retrospective study was conducted for four months (March−June 2021) in the autonomous province of Vojvodina in Serbia on 11,372 patients using reverse-transcription polymerase chain reaction or antigen-detection rapid diagnostic tests verifying COVID-19 in those aged ≥65 years. Demographics, comorbidities, disease severity, and final outcomes were evaluated in fully vaccinated compared to unvaccinated individuals. Individuals were divided into younger-old (65−74 years) and older-old (≥75 years) age groups and differences between those groups were further evaluated. Binary logistic regression was performed to identify independent predictors of poor outcome. RESULTS: By the end of the research, 51.3% of the population of APV 65−74 years, as well as 46.2% of those older than 74 years, were vaccinated. From the acquired sample, 17.4% had breakthrough infection. Asymptomatic forms were higher in both age groups of vaccinated vs. unvaccinated (3.9%­younger-old, 6.3%­older-old vs. 2.9%­younger-old, 3.9%­older-old). The same results were registered with mild symptoms (82.1%­younger-old, 68.1%­older-old vs. 76.3%­younger-old, 57.5%­older-old) (p < 0.001). The case fatality ratio of the vaccinated population was smaller than the unvaccinated population in both groups (3.1% vs. 7.9%­younger-old; 11.4% vs. 22.5%­older-old) (p < 0.001). The odds ratio for poor outcome in unvaccinated individuals was 2.3 (95% confidence interval, p < 0.001) for the total sample. CONCLUSIONS: An increase in asymptomatic and mild forms, as well as decrease in severe or critical forms and poor outcomes, were noted in the vaccinated population. Choosing to avoid vaccination against SARS-CoV-2 may increase the chance of poor outcome in older individuals.

Human primary chronic wound derived fibroblasts demonstrate differential pattern in expression of fibroblast specific markers, cell cycle arrest and reduced proliferation.

INTRODUCTION: Although wound refers to simple cut in the skin, most wounds don't heal because of the various local and systemic factors that lead to its complexity and chronicity. Thus, prior understanding of the status of the wound is necessary and methods that can differentiate between the healing and non-healing wounds at a much earlier stage is crucial for a successful treatment. METHODS: The current study aims at differentiating Acute Wound Fibroblasts (AWFs) and Chronic Wound Fibroblasts (CWFs) based on differential expression of fibroblast specific markers such as Vimentin and Alpha Smooth Muscle Actin (α-SMA) and compare its cell cycle and proliferation. RESULTS: Immunostaining and western blotting analysis showed that, AWFs and CWFs differentially expressed vimentin and α-SMA, with AWFs and CWFs showing higher expression of vimentin and α-SMA respectively. AWFs showed higher distributions in G0/G1 (67.43% vs. 62.16%), S phase (22.61% vs. 8.51%) compared to CWFs. However, AWFs showed decreased distributions compared to CWFs in G2 + M phase (8.14% vs. 10.6%). Thus, it was observed that CWFs showed cell cycle arrest in the G1/G0 phase and inhibited DNA synthesis, which was further confirmed by reduced proliferation of CWFs. We suggest that, differential expression of the cell specific markers can be attributed to its pathophysiological status and chronicity of the wound and reduced proliferation rate of CWFs is due to lesser expression of vimentin, which is a key protein for in vitro cell proliferation. CONCLUSIONS: Outcome of the study serve as an immunological tool to guide the chronicity of the wound, which helps to understand the wound towards design of personalized care. The findings also represent a promising opportunity to gain insight into how cell cycle arrest can impact on wound healing and clinical outcomes.

Health Care Resource Utilization and Total Costs of Care Among Patients with Diffuse Large B Cell Lymphoma Treated with Chimeric Antigen Receptor T Cell Therapy in the United States.

The use of chimeric antigen receptor (CAR) T-cell therapy after a second relapse of diffuse large B-cell lymphoma (DLBCL) has shown favorable efficacy in clinical trials; however, little is known about health care resource utilization (HCRU) and costs of CAR T cell therapy for patients treated in real-world settings. We assessed treatment patterns, HCRU, costs, and safety in patients receiving CAR T cell therapy for relapsed or refractory DLBCL across 3 US commercial claims databases. Adults with DLBCL treated with CAR T cell therapy were identified in the following 3 claims databases: Optum® Clinformatics® Data Mart, IBM MarketScan® Commercial & Medicare Database, and IQVIA PharMetrics® Plus. Mean total costs were calculated and adjusted to 2019 US dollars. HCRU and costs within 3 months of infusion were stratified by safety events of interest, including neurological events (NEs) and cytokine release syndrome (CRS), identified via unvalidated algorithms designed based on expert medical opinion. A total of 191 patients receiving CAR T cell therapy were identified across the databases; their median age ranged from 56 to 67 years, and 63% to 75% were male. Most patients (88% to 98%) received CAR T cell infusions in the inpatient setting; 30% to 75% received bridging therapy. CRS was reported in 75% to 84% of patients (severe CRS, 15% to 32%), and NEs were reported in 58% to 69% (severe NEs, 25% to 43%). Mean total inpatient hospital days ranged from 17 to 22 days and increased with severe CRS (19 to 27 days) or severe NEs (22 to 29 days). Mean total health care expenditures ranged from $380,000 to $526,000 and were generally higher with severe CRS or NEs (∼$406,000 to $679,000). HCRU and costs associated with CAR T cell therapy may vary in the real world depending on several factors, including occurrence and severity of adverse events.

Health State Utilities for Adverse Events Associated with Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy provides effective treatment for large B-cell lymphoma (LBCL). Cost-utility analyses examining and comparing the value of these treatments require health state utilities representing key characteristics to differentiate among therapies. This study estimated utilities for adverse events (AEs) associated with CAR T-cell therapy, including cytokine release syndrome (CRS) and neurological events (NEs). METHODS: Health state vignettes were drafted based on literature review, AE reports from a trial of CAR T-cell therapy, and clinician input. Health states were valued in time trade-off interviews with general population participants in the UK. The first vignette described relapsed/refractory LBCL treated with CAR T-cell therapy without AEs. Five other vignettes had the same LBCL and treatment description, with the addition of an AE. Disutilities (i.e., utility decrease) associated with these AEs were calculated by subtracting the utility of the health state without AEs from those of the other health states. RESULTS: Interviews were completed with 218 participants (50% male; mean age 49 years). Mean (standard deviation [SD]) utility for CAR T-cell therapy without AEs was 0.73 (0.30). Mean (SD) disutilities associated with CRS were -0.01 (0.04) for grade 1, -0.05 (0.09) for grade 2, and -0.23 (0.24) for grade 3/4. Mean (SD) disutilities associated with NEs were -0.04 (0.07) for grade 1/2 and -0.18 (0.22) for grade 3/4. CONCLUSIONS: More severe AEs were associated with greater disutilities. Health state utilities estimated in this study may be useful in cost-effectiveness models examining the value of CAR T-cell therapy in patients with LBCL.

Risks of mucormycosis in the current Covid-19 pandemic: a clinical challenge in both immunocompromised and immunocompetent patients.

Mucormycosis, also called "Black Fungus", is a new cause for worry in the current Coronavirus disease 2019 (covid-19) pandemic. Mucormycosis is devasting due to its high rate of morbidity and mortality which is a great cause of concern. Mucormycosis, in general, affects immunocompromised patients including diabetic, people with malignancies, organ and stem cell transplants and people affected with pandemic diseases like covid-19. Diagnosis of Mucormycosis is often delayed either due to clinical complications or misdiagnosed as symptoms of other diseases, especially covid-19. This could delay the treatment protocol which results in the failure of treatment. Mortality rate due to secondary infections in covid-19 patients with uncontrolled diabetics and who are on steroid therapy can soon reach 100% if diagnosis and treatment doesn't happen on timely basis. Risk of Mucormycosis is not just in immunosuppressed patients, but immunocompetent people with late diagnosis are also prone to infection. In view of this, we present a comprehensive review on risks of Mucormycosis in immunocompromised and immunocompetent patients highlighting the epidemiology, forms of Mucormycosis, immune response against Mucorales, difficulties in diagnosis and challenges in treatment of Mucormycosis, with emphasis on covid-19 associated Mucormycosis. Importantly, we have discussed the precautions and care to effectively manage Mucormycosis in immunocompromised and immunocompetent patients. Thus, current review helps clinicians in understanding various risk factors in both immunocompromised (especially covid-19 patients) and immunocompetent patients which is critical in managing Mucormycosis in current covid-19 pandemic.

Stop Drill, Make a Change: An In Vivo Study.

BACKGROUND: The chemomechanical method of caries removal is a modality that is non-invasive, cost-effective, and if some caries preventive measures could be added to them, then it might render the remaining dentin more resistant to future caries attacks also. Thereby, this study is conducted to evaluate the in vivo aspect of newly developed "one man army material-Apacaries gel". AIM AND OBJECTIVE: To evaluate and compare the antimicrobial efficacy, efficiency, and pain perception of a chemomechanical caries removal agent (Apacaries gel) with a conventional method. DESIGN: Twenty children (aged 6-12 years) with bilateral occlusal caries making a sample size of 40 were included in the study. Group I: caries removal using rotary instruments and Group II: caries removal using Apacaries gel (n = 20 each). Caries removal time and pain perception were measured using a stopwatch and Wong-Baker Pain Scale. Dentin samples of both groups were taken before and after caries removal for microbiological analysis. STATISTICAL ANALYSIS USED: The data were statistically analyzed using the Student's t-test to compare the two groups. RESULTS: There was a non-significant difference in bacterial count while a significant difference was seen in time consumption and pain perception in both methods of caries removal. CONCLUSION: Chemomechanical caries removal (Apacaries gel) can be an effective clinical alternative treatment for caries removal in children. KEY MESSAGES: It is the only in vivo study on "Apacaries gel-a one man army" which eliciting the unique property of prevention of dental caries. HOW TO CITE THIS ARTICLE: Dogra M, Gupta MP, Sheikh T, et al. Stop Drill, Make a Change: An In Vivo Study. Int J Clin Pediatr Dent 2021;14(2):258-262.

Travel-Related Economic Burden of Chimeric Antigen Receptor T Cell Therapy Administration by Site of Care.

INTRODUCTION: We previously examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacted patient travel distances and time. In the current study, we estimated travel-related economic burden associated with site-of-care options among patients with relapsed/refractory diffuse large B cell lymphoma. METHODS: We used geographic information system methods to quantify travel-related economic burden across three site-of-care scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Socioeconomic status, administration sites, and county of residence were derived from the US Census Bureau and publicly available sources. Travel costs were based on governmental guidelines, US census wage data, and Bureau of Transportation Statistics. Travel distance and time to the nearest CAR T cell therapy administration sites were estimated from previous research. RESULTS: Total national estimated costs associated with traveling for CAR T cell therapy were $21.1 million if CAR T cell therapy was offered exclusively in academic hospitals, and $14.7 million if expanded to include community hospitals plus nonacademic specialty oncology network centers, representing a $6.5-million reduction associated with expanding access to eligible patients. The largest cost-saving component was lodging/meals. Regional and demographic cost differences were statistically significant between academic hospitals and nonacademic hospitals/specialty oncology centers. In all scenarios, patients living below the federal poverty level (FPL) had higher weighted mean total costs versus patients living above the FPL. White and Native American patients were estimated to have the highest weighted mean total costs across race/ethnicity groups. For all subgroups, costs were reduced by expanding access beyond academic hospitals. CONCLUSION: CAR T cell therapy is currently restricted to academic hospitals; total travel costs could be substantially decreased if access is expanded to nonacademic hospitals and specialty oncology centers. Patients in rural areas and those living below the FPL are particularly disadvantaged by restricted access.

Access to Chimeric Antigen Receptor T Cell Therapy for Diffuse Large B Cell Lymphoma.

INTRODUCTION: Geographic access to novel oncology therapies, and the extent to which it may vary by potential sites of care, regions, and population characteristics, is poorly understood. We examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacts patient travel distances and time. METHODS: We used geographic information system techniques to calculate shortest travel distance and time between patients with relapsed/refractory diffuse large B cell lymphoma (DLBCL) and the nearest CAR T cell therapy administration site in three scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Main outcome measures were differences in travel distance and time among the scenarios and the relationship between travel time and socioeconomic status, race, rural-urban areas, and non-Hodgkin lymphoma clusters. Non-Hodgkin lymphoma incidence, socioeconomic status, and administration centers were derived from governmental/publicly available data sources. RESULTS: Of 3922 patients eligible for CAR T cell therapy, more than 37% had to travel more than 1 h to the nearest academic hospital. Average travel time and distance were significantly reduced by 23% and 30% (P < 0.001), respectively, when access was expanded to include community hospitals plus a broader range of oncology specialty treatment centers. Compared to academic hospitals alone, increasing access to include community hospitals decreased time and distance by 7% and 8% (P < 0.01), respectively. In addition, there would be a lower proportion of sites operating as the only care provider within 25 miles if access was expanded outside of academic hospitals only. Longer travel time was associated with lower socioeconomic status. CONCLUSION: Many patients with DLBCL have long travel times to an academic hospital that administers CAR T cell therapy. Expanding access to care through site-of-care planning will help address regional, rural-urban, and sociodemographic equity in the geographic allocation of CAR T cell therapy.

Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel-treated patients in the TRANSCEND NHL 001 trial.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell-specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.