Antibodies to Borrelia burgdorferi and Bartonella species in serum and synovial fluid from people with rheumatic diseases.

Vector-borne infections may underlie some rheumatic diseases, particularly in people with joint effusions. This study aimed to compare serum and synovial fluid antibodies to B. burgdorferi and Bartonella spp. in patients with rheumatic diseases. This observational, cross-sectional study examined paired synovial fluid and serum specimens collected from 110 patients with joint effusion between October 2017 and January 2022. Testing for antibodies to B. burgdorferi (using CDC criteria) and Bartonella spp. via two indirect fluorescent antibody (IFA) assays was performed as part of routine patient care at the Institute for Specialized Medicine (San Diego, CA, USA). There were 30 participants (27%) with positive two-tier B. burgdorferi serology and 26 participants (24%) with IFA seroreactivity (≥1:256) to B. henselae and/or B. quintana. Both B. burgdorferi IgM and IgG were detected more frequently in synovial fluid than serum: 27% of patients were either IgM or IgG positive in synovial fluid, compared to 15.5% in serum (P = 0.048). Conversely, B. henselae and B. quintana antibodies were detected more frequently in serum than synovial fluid; overall only 2% of patients had positive IFA titers in synovial fluid, compared to 24% who had positive IFA titers in serum (P < 0.001). There were no significant associations between B. burgdorferi or Bartonella spp. seroreactivity with any of the clinical rheumatological diagnoses. This study provides preliminary support for the importance of synovial fluid antibody testing for documenting exposure to B. burgdorferi but not for documenting exposure to Bartonella spp. IMPORTANCE: This study focuses on diagnostic testing for two common vector-borne diseases in an affected patient population. In it, we provide data showing that antibodies to B. burgdorferi, but not Bartonella spp., are more commonly found in synovial fluid than serum of patients with joint effusion. Since Lyme arthritis is a common-and sometimes difficult to diagnose-rheumatic disease, improving diagnostic capabilities is of utmost importance. While our findings are certainly not definitive for changes to practice, they do suggest that synovial fluid could be a useful sample for the clinical diagnosis of Lyme disease, and future prospective studies evaluating this claim are warranted.

Active compensation for changes in TDH3 expression mediated by direct regulators of TDH3 in Saccharomyces cerevisiae.

Genetic networks are surprisingly robust to perturbations caused by new mutations. This robustness is conferred in part by compensation for loss of a gene's activity by genes with overlapping functions, such as paralogs. Compensation occurs passively when the normal activity of one paralog can compensate for the loss of the other, or actively when a change in one paralog's expression, localization, or activity is required to compensate for loss of the other. The mechanisms of active compensation remain poorly understood in most cases. Here we investigate active compensation for the loss or reduction in expression of the Saccharomyces cerevisiae gene TDH3 by its paralog TDH2. TDH2 is upregulated in a dose-dependent manner in response to reductions in TDH3 by a mechanism requiring the shared transcriptional regulators Gcr1p and Rap1p. TDH1, a second and more distantly related paralog of TDH3, has diverged in its regulation and is upregulated by another mechanism. Other glycolytic genes regulated by Rap1p and Gcr1p show changes in expression similar to TDH2, suggesting that the active compensation by TDH3 paralogs is part of a broader homeostatic response mediated by shared transcriptional regulators.

Coronary Artery and Peripheral Vascular Disease in a Patient with Poorly Differentiated Thyroid Cancer Treated with the Tyrosine Kinase Inhibitor Lenvatinib.

A subset of patients with differentiated thyroid carcinoma develop radioiodine refractory (RAIR) incurable disease, which typically has a poor prognosis. The multitargeted tyrosine kinase inhibitor lenvatinib has demonstrated significant improvements in progression-free survival in RAIR thyroid cancers compared to placebos. However, in the phase III SELECT trial of the drug in thyroid cancer, 5.4% of patients on lenvatinib experienced arterial thromboembolic events, with 2.7% experiencing severe grade ≥3 toxicities associated with arterial vascular events. This case study reports a patient with metastatic poorly differentiated follicular thyroid cancer who developed significant obstructive coronary artery disease following initiation of lenvatinib treatment, despite no predisposing cardiovascular risk factors apart from a remote smoking history. The possibility of developing coronary or peripheral artery disease should be considered in patients who are on targeted therapies, such as lenvatinib, even in the absence of traditional cardiovascular risk factors. In addition, baseline cardiac risk assessment and early treatment should be pursued to minimize interruptions to potentially lifesaving cancer therapy.

Morphoelectric and transcriptomic divergence of the layer 1 interneuron repertoire in human versus mouse neocortex.

Neocortical layer 1 (L1) is a site of convergence between pyramidal-neuron dendrites and feedback axons where local inhibitory signaling can profoundly shape cortical processing. Evolutionary expansion of human neocortex is marked by distinctive pyramidal neurons with extensive L1 branching, but whether L1 interneurons are similarly diverse is underexplored. Using Patch-seq recordings from human neurosurgical tissue, we identified four transcriptomic subclasses with mouse L1 homologs, along with distinct subtypes and types unmatched in mouse L1. Subclass and subtype comparisons showed stronger transcriptomic differences in human L1 and were correlated with strong morphoelectric variability along dimensions distinct from mouse L1 variability. Accompanied by greater layer thickness and other cytoarchitecture changes, these findings suggest that L1 has diverged in evolution, reflecting the demands of regulating the expanded human neocortical circuit.

Signature morphoelectric properties of diverse GABAergic interneurons in the human neocortex.

Human cortex transcriptomic studies have revealed a hierarchical organization of γ-aminobutyric acid-producing (GABAergic) neurons from subclasses to a high diversity of more granular types. Rapid GABAergic neuron viral genetic labeling plus Patch-seq (patch-clamp electrophysiology plus single-cell RNA sequencing) sampling in human brain slices was used to reliably target and analyze GABAergic neuron subclasses and individual transcriptomic types. This characterization elucidated transitions between PVALB and SST subclasses, revealed morphological heterogeneity within an abundant transcriptomic type, identified multiple spatially distinct types of the primate-specialized double bouquet cells (DBCs), and shed light on cellular differences between homologous mouse and human neocortical GABAergic neuron types. These results highlight the importance of multimodal phenotypic characterization for refinement of emerging transcriptomic cell type taxonomies and for understanding conserved and specialized cellular properties of human brain cell types.

The projection-specific signals that establish functionally segregated dopaminergic synapses.

Dopaminergic projections regulate various brain functions and are implicated in many neuropsychiatric disorders. There are two anatomically and functionally distinct dopaminergic projections connecting the midbrain to striatum: nigrostriatal, which controls movement, and mesolimbic, which regulates motivation. However, how these discrete dopaminergic synaptic connections are established is unknown. Through an unbiased search, we identify that two groups of antagonistic TGF-ß family members, bone morphogenetic protein (BMP)6/BMP2 and transforming growth factor (TGF)-ß2, regulate dopaminergic synapse development of nigrostriatal and mesolimbic neurons, respectively. Projection-preferential expression of their receptors contributes to specific synapse development. Downstream, Smad1 and Smad2 are specifically activated and required for dopaminergic synapse development and function in nigrostriatal vs. mesolimbic projections. Remarkably, Smad1 mutant mice show motor defects, whereas Smad2 mutant mice show lack of motivation. These results uncover the molecular logic underlying the proper establishment of functionally segregated dopaminergic synapses and may provide strategies to treat relevant, projection-specific disease symptoms by targeting specific BMPs/TGF-ß and/or Smads.

'It feels like I'm back to being a teacher': A longitudinal trajectory analysis of teachers' experiences during the first 8 months of COVID-19 in England.

BACKGROUND: Understanding teachers' experiences throughout the school closures and reopenings that have characterized large periods of the COVID-19 pandemic provides us with unique insights into what it means to be a teacher during a global public health crisis. AIM AND METHOD: To investigate teachers' narratives of their experiences, we conducted 95 semi-structured interviews with 24 teachers in England across four time points between April and November 2020. We used a longitudinal qualitative trajectory analysis of participants' stories of their high-, low- and turning-points. RESULTS: We derived four themes that were evident at each time point and developed over time. The themes were: (1) growing frustration at uncertainties caused by poor government leadership, (2) expanding concern for pupil learning and well-being, (3) an increasingly labour-intensive and exhausting job and (4) declining pleasure and pride in being a teacher. CONCLUSIONS: The findings shed light on the impact of COVID-19 on the professional identity of these teachers and we propose ways in which teachers can be supported now and in the future.

The association of host and vector characteristics with Ctenocephalides felis pathogen and endosymbiont infection.

Surveillance of the fleas and flea-borne pathogens infecting cats is important for both human and animal health. Multiple zoonotic Bartonella and Rickettsia species are known to infect the most common flea infesting cats and dogs worldwide: Ctenocephalides felis, the cat flea. The ability of other flea species to transmit pathogens is relatively unexplored. We aimed to determine cat host and flea factors independently associated with flea Bartonella and Rickettsia infection. We also assessed flea and cat infection by flea-host pair and location. To accomplish these aims, we performed qPCR for the detection of Bartonella, hemotropic Mycoplasma, Rickettsia, and Wolbachia DNA using paired cat and flea samples obtained from free-roaming cats presenting for spay or neuter across four locations in the United States. A logistic regression model was employed to identify the effect of cat (sex, body weight, geographic location, and Bartonella, hemotropic Mycoplasma, and Rickettsia spp., infection) and flea (clade and Rickettsia and Wolbachia infection) factors on C. felis Bartonella clarridgeiae infection. From 189 free roaming cats, we collected 84 fleas: Ctenocephalides felis (78/84), Cediopsylla simplex (4/84), Orchopeas howardi (1/84), and Nosopsyllus fasciatus (1/84). Ctenocephalides felis were phylogenetically assigned to Clades 1, 4, and 6 by cox1 gene amplification. Rickettsia asembonensis (52/84) and B. clarridgeiae (16/84) were the most common pathogenic bacteria detected in fleas. Our model identified host cat sex and weight as independently associated with B. clarridgeiae infection in fleas. Rickettsia asembonensis (52/84), Rickettsia felis (7/84) and Bartonella henselae (7/84) were detected in specific clades: R. felis was detected only in Clades 1 and 6 while B. henselae and R. asembonensis were detected only in Clade 4. Wolbachia spp., also displayed clade specificity with strains other than Wolbachia wCfeT only infecting fleas from Clade 6. There was poor flea and host agreement for Bartonella spp., infection; however, there was agreement in the Bartonella species detected in cats and fleas by geographic location. These findings reinforce the importance of considering reservoir host attributes and vector phylogenetic diversity in epidemiological studies of flea-borne pathogens. Widespread sampling is necessary to identify the factors driving flea-borne pathogen presence and transmission.

Adapting Family Planning Service Delivery in Title X and School-Based Settings during COVID-19: Provider and Staff Experiences.

The COVID-19 pandemic introduced urgent and unique challenges to family planning providers and staff in ensuring continued access to high-quality services, particularly for groups who experience greater barriers to accessing services, such as women with systemically marginalized identities and adolescents and young adults (AYA). While research has documented key adaptations made to service delivery during the early phase of the pandemic, limited studies have used qualitative methods. This paper draws on qualitative interview data from family planning providers and staff in Title-X-funded clinics and school-based clinics-two settings that serve populations that experience greater barriers to accessing care-to (a) describe the adaptations made to service delivery during the first year of the pandemic and (b) explore provider and staff experiences and impressions implementing these adaptations. In-depth interviews were conducted with 75 providers and staff between February 2020 and February 2021. Verbatim transcripts were analyzed via inductive content analysis followed by thematic analysis. Four key themes were identified: (1) Title-X- and school-based staff made multiple, concurrent adaptations to continue family planning services; (2) providers embraced flexibility for patient-centered care; (3) school-based staff faced unique challenges to reaching and serving youth; and (4) COVID-19 created key opportunities for innovation. The findings suggest several lasting changes to family planning service delivery and provider mindsets at clinics serving populations hardest hit by the pandemic. Future studies should evaluate promising practices in family planning service delivery-including telehealth and streamlined administrative procedures-and explore how these are experienced by diverse patient populations, particularly AYA and those in areas where privacy or internet access are limited.

Hypertensive events after the initiation of contemporary cancer therapies for breast cancer control.

BACKGROUND: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown. METHODS: Leveraging two large U.S.-based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension-related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting-odds-ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug-class, and individual drugs with the likelihood of excess hypertension. RESULTS: Overall, there were 5,464,401 BC-admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in-hospital mortality, which equilibrated over time. The mean incidence of hypertension-related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non-cancer patients (RR 7.71, p < 0.001). Moreover, in FAERS, those with hypertension versus other BC-treatment side-effects were more frequently hospitalized (40.1% vs. 36.7%, p < 0.001), and were most commonly associated with chemotherapy (45.9%). Outside of Eribulin (ROR 3.36; 95% CI 1.37-8.22), no specific drug was associated with a higher reporting of hypertension; however, collectively BC drugs were associated with a higher odds of hypertension (ROR 1.66; 95% CI 1.09-2.53). CONCLUSIONS: BC therapies are associated with a substantial increase in limiting hypertension.

Eosinophilic Myocarditis Presenting as Cardiac Tamponade: A Diagnostic Challenge.

Eosinophilic myocarditis (EM) is a rare cause of acute heart failure. It can occur secondary to drug hypersensitivity, autoimmune diseases such as vasculitis, idiopathic hypereosinophilic syndrome (HES) or malignancy, but is often under-recognized and underdiagnosed, being confused with other causes of heart failure. While EM is associated with various clinical symptoms, it is rarely associated with cardiac tamponade that requires urgent pericardiocentesis. Here we describe a patient with EM who presented with cardiac tamponade and decompensated heart failure likely secondary to autoimmune disease. LEARNING POINTS: Work-up for hypereosinophilia should include the identification of treatable causes as well as end-organ dysfunction requiring urgent treatment.In patients presenting with acute heart failure and cardiac tamponade of unclear aetiology, eosinophilic myocarditis should be considered whether or not hypereosinophilia is present on presentation.When invoking the diagnosis of eosinophilic myocarditis, extensive efforts should be made to identify primary causes, such as autoimmune conditions including vasculitis.

Women's experiences with person-centered family planning care: Differences by sociodemographic characteristics.

Objective: Person-centered contraceptive care is associated with positive reproductive health outcomes. Our objective was to analyze patients' ratings on the newly developed Person-Centered Contraceptive Counseling scale (PCCC) to provide distributions for a nationally representative population and to assess differences by sociodemographic characteristics. Study design: Using data from 2017 to 2019 National Survey of Family Growth (NSFG), we analyzed ratings across the four PCCC items among 2242 women who received contraceptive counseling in the past year. Items measured patients' reports of how providers respected them, let them describe their contraceptive preferences, took their preferences seriously, and adequately informed them about their options. We studied each PCCC item individually as well as the combined scale, distinguishing between ratings of "excellent" versus lower ratings. Bivariate and multivariate logistic regression models assessed how patients' characteristics (age, race/ethnicity and English proficiency, sexual orientation, income, and parity) and provider type were associated with the likelihood of experiencing person-centered care. Results: The majority of women (59%-69%) reported that their family planning provider was "excellent" across the four PCCC items and just over half (51%) reported "excellent" on all items. In multivariate analyses, having a lower income, Black race, non-heterosexual identity, and Hispanic ethnicity combined with low English proficiency were associated with lower PCCC ratings. Conclusions: In a nationally representative sample, the PCCC captured variation in women's experiences with person-centered family planning care by sociodemographic characteristics. Findings highlight the need for contraceptive counseling that centers on clients' preferences and experiences, particularly for patients who belong to groups experiencing health inequities. Implications: Person-centered care is a key component of high-quality family planning services. This analysis highlights sociodemographic disparities in person-centered care by analyzing PCCC ratings. Findings show the value of this new health care performance measure and affirm the need for family planning care that centers individuals' preferences and lived experiences.

Sustained Oncogenic Signaling in the Cytostatic State Enables Targeting of Nonproliferating Persistent Cancer Cells.

Many advanced therapeutics possess cytostatic properties that suppress cancer cell growth without directly inducing death. Treatment-induced cytostatic cancer cells can persist and constitute a reservoir from which recurrent growth and resistant clones can develop. Current management approaches primarily comprise maintenance and monitoring because strategies for targeting nonproliferating cancer cells have been elusive. Here, we used targeted therapy paradigms and engineered cytostatic states to explore therapeutic opportunities for depleting treatment-mediated cytostatic cancer cells. Sustained oncogenic AKT signaling was common, while nonessential, in treatment-mediated cytostatic cancer cells harboring PI3K-pathway mutations, which are associated with cancer recurrence. Engineering oncogenic signals in quiescent mammary organotypic models showed that sustained, aberrant activation of AKT sensitized cytostatic epithelial cells to proteasome inhibition. Mechanistically, sustained AKT signaling altered cytostatic state homeostasis and promoted an oxidative and proteotoxic environment, which imposed an increased proteasome dependency for maintaining cell viability. Under cytostatic conditions, inhibition of the proteasome selectively induced apoptosis in the population with aberrant AKT activation compared with normal cells. Therapeutically exploiting this AKT-driven proteasome vulnerability was effective in depleting treatment-mediated cytostatic cancer cells independent of breast cancer subtype, epithelial origin, and cytostatic agent. Moreover, transient targeting during cytostatic treatment conditions was sufficient to reduce recurrent tumor growth in spheroid and mouse models. This work identified an AKT-driven proteasome-vulnerability that enables depletion of persistent cytostatic cancer cells harboring PTEN-PI3K pathway mutations, revealing a viable strategy for targeting nonproliferating persistent cancer cell populations before drug resistance emerges. SIGNIFICANCE: This study finds that sustained oncogenic signaling in therapy-induced cytostatic cancer cells confers targetable vulnerabilities to deplete persistent cancer cell populations and reduce cancer recurrence.

A Unified Protocol to Streamline Molecular and Cellular Analysis for Three-Dimensional Cell Cultures.

Three-dimensional (3D) cell cultures based on reconstituted basement membrane materials recapitulate features of extracellular matrix (ECM) and tissue stiffness in vivo and provide a physiologically relevant platform to study complex cellular processes, such as stem cell differentiation and tissue morphogenesis, that are otherwise difficult in animal models. The form and composition of 3D matrices in culture can interfere with and pose challenges for different experimental setups and assays, which necessitate alterations to facilitate analysis. Here, we provide a unified protocol for 3D cell cultures with modular workflows that streamline procedures for compatibility with common molecular and cellular assays such as live-cell imaging, immunofluorescence , qPCR, RNAseq, western blotting, and quantitative mass spectrometry.

Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting.

Major immunotherapy challenges include a limited number of predictive biomarkers and the unusual imaging features post-therapy, such as pseudo-progression, which denote immune infiltrate-mediated tumor enlargement. Such phenomena confound clinical decision-making, since the cancer may eventually regress, and the patient should stay on treatment. We prospectively evaluated serial, blood-derived cell-free DNA (cfDNA) (baseline and 2-3 weeks post-immune checkpoint inhibitors [ICIs]) for variant allele frequency (VAF) and blood tumor mutation burden (bTMB) changes (next-generation sequencing) (N = 84 evaluable patients, diverse cancers). Low vs. high cfDNA-derived average adjusted ΔVAF (calculated by a machine-learning model) was an independent predictor of higher clinical benefit rate (stable disease ≥6 months/complete/partial response) (69.2% vs. 22.5%), and longer median progression-free (10.1 vs. 2.25 months) and overall survival (not reached vs. 6.1 months) (all P < .001, multivariate). bTMB changes did not correlate with outcomes. Therefore, early dynamic changes in cfDNA-derived VAF were a powerful predictor of pan-cancer immunotherapy outcomes.

Local connectivity and synaptic dynamics in mouse and human neocortex.

We present a unique, extensive, and open synaptic physiology analysis platform and dataset. Through its application, we reveal principles that relate cell type to synaptic properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Synaptic properties are heterogeneous in most subclass-to-subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, whereas the strength axis accounts for substantial heterogeneity within the subclass. In the human cortex, excitatory-to-excitatory synaptic dynamics are distinct from those in the mouse cortex and vary with depth across layers 2 and 3.

Incorporating Competencies Related to Project Management into the Joint Taskforce Core Competency Framework for Clinical Research Professionals.

In 2014, the Joint Task Force for Clinical Trial Competency (JTF) published its Core Competency Framework. The Framework has been utilized internationally by academic institutions, corporate entities, professional associations, educational and training programs, and regulatory agencies and integrated into their activities. The JTF has continually updated and expanded the scope of the Framework to reflect changes in the scientific understanding and methodology utilized in conducting clinical research. In 2019, representatives from the Drug Information Association Professional Development and Project Management Leadership Communities approached the JTF reflecting the importance of clinical project managers and the project management skill set to the clinical research enterprise. In response, the JTF created a Project Management Competency Task Force to define and document these core competencies with recommendations for their inclusion as a revision to the Framework 3.0. Two new specific competencies with related examples were incorporated into Revision 3.1 and expressed at the Basic, Skilled and Advanced levels. In addition, the wording of several existing competencies was modified, and related examples added to reflect the knowledge, skills, and attitudes of clinical project managers.

Examining Partnership Approaches for Engaging Fathers to Address Domestic Violence.

Little is known about partnerships fatherhood programs establish to engage fathers in addressing domestic violence (DV). The study aimed to (a) describe partnership activities between fatherhood programs and organizations that address DV, (b) highlight strategies for productive partnerships, and (c) identify areas in need of improvement for addressing DV. This study discusses findings from qualitative interviews with 27 individuals from 17 fatherhood and DV organizations across the United States including the variety of partnership activities used to prevent and address DV (e.g., conducting trainings or facilitating referrals); strategies for creating productive partnerships; and partnership areas that need further attention.

"My brain feels like a browser with 100 tabs open": A longitudinal study of teachers' mental health and well-being during the COVID-19 pandemic.

BACKGROUND: Teaching and caring for pupils during the COVID-19 pandemic has been a challenge for many teachers, and its impact on teachers' mental health and well-being (MHWB) should be of great national and international concern. AIM AND PARTICIPANTS: This study examines 24 primary and secondary school teachers' MHWB experiences across three time points (April, July, and November 2020) using longitudinal qualitative trajectory analysis. METHOD: We used a mixture of inductive and deductive coding, based on the Job Demands-Resources Model, to identify the job demands (aspects of the job that can be physically or psychologically costly) and job resources (aspects of the job that can buffer the effects of job demands and promote achievement and growth) teachers reported experiencing across the three time points. RESULTS: Generally, teachers' MHWB seemed to have declined throughout the pandemic, especially for primary school leaders. Six job demands contributed negatively to teachers' MHWB (i.e., uncertainty, workload, negative perception of the profession, concern for others' well-being, health struggles, and multiple roles) and three job resources contributed positively to their MHWB (i.e., social support, work autonomy, and coping strategies). CONCLUSIONS: Policymakers and practitioners can support teachers' MHWB by engaging in more collaborative communication and ensuring greater accessibility to sources of social support. These discussions and provisions will be crucial in supporting teachers, and thereby the educational system, both during and after the pandemic.

Assessing CAR T-Cell Therapy Response Using Genome-Wide Sequencing of Cell-Free DNA in Patients With B-Cell Lymphomas.

Methods that enable monitoring of therapeutic efficacy of autologous chimeric antigen receptor (CAR) T-cell therapy will be clinically useful. The aim of this study is to demonstrate the feasibility of blood-derived cell-free DNA (cfDNA) to predict CAR T-cell therapy response in patients with refractory B-cell lymphomas. Whole blood was collected before and throughout CAR T-cell therapy until day 154. Low-coverage (∼0.4×), genome-wide cfDNA sequencing, similar to that established for noninvasive prenatal testing, was performed. The genomic instability number (GIN) was used to quantify plasma copy number alteration level. Twelve patients were enrolled. Seven (58%) patients achieved a complete response (CR); 2 (25%), a partial response. Median progression-free survival was 99 days; median overall survival was not reached (median follow-up, 247 days). Altogether, 127 blood samples were analyzed (median, 10 samples/patient [range 8-13]). All 5 patients who remained in CR at the time of last measurement had GIN <170 (threshold). Two patients who attained CR, but later relapsed, and all but one patient who had best response other than CR had last GIN measurement of >170. In 5 of 6 patients with relapsed or progressive disease, increasing GIN was observed before the diagnosis by imaging. The abundance of CAR T-cell construct (absolute number of construct copies relative to the number of human genome equivalents) also showed a trend to correlate with outcome (day 10, P = .052). These data describe a proof-of-concept for the use of multiple liquid biopsy technologies to monitor therapeutic response in B-cell lymphoma patients receiving CAR T-cell therapy.