Comparison of EV characterization by commercial high-sensitivity flow cytometers and a custom single-molecule flow cytometer.

High-sensitivity flow cytometers have been developed for multi-parameter characterization of single extracellular vesicles (EVs), but performance varies among instruments and calibration methods. Here we compare the characterization of identical (split) EV samples derived from human colorectal cancer (DiFi) cells by three high-sensitivity flow cytometers, two commercial instruments, CytoFLEX/CellStream, and a custom single-molecule flow cytometer (SMFC). DiFi EVs were stained with the membrane dye di-8-ANEPPS and with PE-conjugated anti-EGFR or anti-tetraspanin (CD9/CD63/CD81) antibodies for estimation of EV size and surface protein copy numbers. The limits of detection (LODs) for immunofluorescence and vesicle size based on calibration using cross-calibrated, hard-dyed beads were ∼10 PE/∼80 nm EV diameter for CytoFLEX and ∼10 PEs/∼67 nm for CellStream. For the SMFC, the LOD for immunofluorescence was 1 PE and ≤ 35 nm for size. The population of EVs detected by each system (di-8-ANEPPS+/PE+ particles) differed widely depending on the LOD of the system; for example, CellStream/CytoFLEX detected only 5.7% and 1.5% of the tetraspanin-labelled EVs detected by SMFC, respectively, and median EV diameter and antibody copy numbers were much larger for CellStream/CytoFLEX than for SMFC as measured and validated using super-resolution/single-molecule TIRF microscopy. To obtain a dataset representing a common EV population analysed by all three platforms, we filtered out SMFC and CellStream measurements for EVs below the CytoFLEX LODs as determined by bead calibration (10 PE/80 nm). The inter-platform agreement using this filtered dataset was significantly better than for the unfiltered dataset, but even better concordance between results was obtained by applying higher cutoffs (21 PE/120 nm) determined by threshold analysis using the SMFC data. The results demonstrate the impact of specifying LODs to define the EV population analysed on inter-instrument reproducibility in EV flow cytometry studies, and the utility of threshold analysis of SMFC data for providing semi-quantitative LOD values for other flow cytometers.

Concurrent loss of LKB1 and KEAP1 enhances SHMT-mediated antioxidant defence in KRAS-mutant lung cancer.

Non-small-cell lung cancer (NSCLC) with concurrent mutations in KRAS and the tumour suppressor LKB1 (KL NSCLC) is refractory to most therapies and has one of the worst predicted outcomes. Here we describe a KL-induced metabolic vulnerability associated with serine-glycine-one-carbon (SGOC) metabolism. Using RNA-seq and metabolomics data from human NSCLC, we uncovered that LKB1 loss enhanced SGOC metabolism via serine hydroxymethyltransferase (SHMT). LKB1 loss, in collaboration with KEAP1 loss, activated SHMT through inactivation of the salt-induced kinase (SIK)-NRF2 axis and satisfied the increased demand for one-carbon units necessary for antioxidant defence. Chemical and genetic SHMT suppression increased cellular sensitivity to oxidative stress and cell death. Further, the SHMT inhibitor enhanced the in vivo therapeutic efficacy of paclitaxel (first-line NSCLC therapy inducing oxidative stress) in KEAP1-mutant KL tumours. The data reveal how this highly aggressive molecular subtype of NSCLC fulfills their metabolic requirements and provides insight into therapeutic strategies.

Magnesium and Esophageal Pain After Peroral Endoscopic Myotomy of the Esophagus: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Postoperative esophageal pain occurs in 67% of patients after peroral endoscopic esophageal myotomy (POEM). Magnesium can act as a smooth muscle relaxant. This study investigated whether intraoperative magnesium can reduce postoperative esophageal pain in patients undergoing POEM. METHODS: In this double-blind, placebo-controlled trial, 92 patients were randomized to receive either magnesium sulfate as a 50 mg.kg-1 (total body weight) bolus followed by an infusion at 25 mg.kg-1.hr-1, or 0.9% saline. Intraoperative analgesia was standardized in all patients. The primary outcome was the score from a validated, modified Esophageal Symptoms Questionnaire (ESQ) in the postanesthesia care unit (PACU). Pain scores, opioid requirements, and questionnaire scores were collected through postoperative day 1. RESULTS: ESQ scores were significantly lower in the magnesium group in the PACU (median [25th-75th], 24 [18-31] vs 35 [28-42]; median difference [95% confidence interval, CI], 10 [6-13]; P < .0001) and on postoperative day 1 (16 [14-23] vs 30 [24-35]; P < .0001). Less opioids were needed in the magnesium group in the PACU (mean ± standard deviation [SD] [99% CI], 4.7 ± 10 [1-9] mg vs 29 ± 21 [21-37] mg; P < .0001) and on postoperative day 1 (1 ± 3.7 [0-2.5] mg vs 13 ± 23 [4-23] mg; P = .0009). Pain scores were lower in the magnesium group in the PACU (0 [0-3] vs 5 [5-7]; P < .0001) and on postoperative day 1 (0 [0-2] vs 4 [3-5]; P < .0001). CONCLUSIONS: Patients undergoing POEM randomized to receive intraoperative magnesium had sustained reductions in esophageal discomfort severity and opioid requirements 24 hours after surgery.

Local Anesthetics, Local Anesthetic Systemic Toxicity (LAST), and Liposomal Bupivacaine.

Local anesthetics have played a vital role in the multimodal analgesia approach to patient care by decreasing the use of perioperative opioids, enhancing patient satisfaction, decreasing the incidence of postoperative nausea and vomiting, decreasing the length of hospital stay, and reducing the risk of chronic postsurgical pain. The opioid-reduced anesthetic management for perioperative analgesia has been largely successful with the use of local anesthetics during procedures such as peripheral nerve blocks and neuraxial analgesia. It is important that practitioners who use local anesthetics are aware of the risk factors, presentation, and management of local anesthetic systemic toxicity (LAST).

Use of once-daily oral semaglutide and associated clinical outcomes among adults with type 2 diabetes in routine clinical practice in Canada: A multicentre, prospective real-world study (PIONEER REAL Canada).

AIM: PIONEER REAL Canada examined real-world clinical outcomes associated with the use of once-daily oral semaglutide in adults with type 2 diabetes. MATERIALS AND METHODS: This was a 34- to 44-week, multicentre, prospective, open-label, non-interventional study in adults who were treatment-naive to injectable glucose-lowering medication and initiated oral semaglutide in routine clinical practice. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to the end of the study (EoS). Secondary endpoints assessed at EoS were change from baseline in body weight (BW); the proportion of participants reaching HbA1c levels <7% and the composite endpoints, HbA1c reduction ≥1% point with BW reduction ≥3% and ≥5%; and treatment satisfaction measured using Diabetes Treatment Satisfaction Questionnaires (DTSQ) status and change. Primary analyses were based on the in-study observation period. RESULTS: In total, 182 participants initiated oral semaglutide (mean age, 58.6 years; HbA1c, 8.0%; BW, 93.7 kg). The estimated changes (95% confidence interval) from baseline to EoS in HbA1c and BW were -1.09% points (-1.24, -0.94; p < .0001) and -7.17% (-8.24, -6.11; p < .0001), respectively. At EoS, 53.7% of participants had HbA1c levels <7%; 39.3% and 31.6% reached HbA1c reduction ≥1% point plus BW reduction ≥3% and ≥5%, respectively. Treatment satisfaction significantly increased (DTSQ status, +4.47 points; DTSQ change, 11.83 points; both p < .0001). At EoS, 75.3% of participants remained on oral semaglutide (55.5% received oral semaglutide 14 mg). No new safety signals were identified for oral semaglutide. CONCLUSIONS: In PIONEER REAL Canada, participants treated with oral semaglutide in routine clinical practice experienced clinically relevant reductions in HbA1c and BW and increased treatment satisfaction.

Spontaneous Adductor Hematoma in a 75-Year-Old Male With Acute Thigh Bruises.

Patients with a history of blood clots are commonly placed on anticoagulation therapy, but a common adverse effect of this therapy is hemorrhage. Our patient with a history of left ventricle thrombus in a free-standing inpatient rehabilitation hospital had ecchymoses that expanded over a large portion of the posterior thigh in one day. The rapid expansion of the ecchymoses coupled with a decline in hemoglobin levels prompted an immediate evaluation that showed an intramuscular hematoma. With hemoglobin levels dropping significantly, the patient was then transferred to the emergency department for higher levels of care. A multidisciplinary team of vascular surgery and electrophysiology physicians decided to discontinue anticoagulation and monitor the hematoma with serial compartment checks. The hematoma had stabilized throughout the hospital stay without surgical intervention. This case will discuss the difficulty of managing a patient with a history of previous blood clots with an adductor magnus hematoma in the setting of concurrent iatrogenic anticoagulation. Furthermore, we will review the current management and evaluation of intramuscular hematomas.

Time to transfer: Long-term effects of a sustained and spiraled content literacy intervention in the elementary grades.

We investigated the effectiveness of a sustained and spiraled content literacy intervention that emphasizes building domain and topic knowledge schemas and vocabulary for elementary-grade students. The model of reading engagement intervention underscores thematic lessons that provide an intellectual structure for helping students connect new learning to a general schema in Grade 1 (animal survival), Grade 2 (scientific investigation of past events like dinosaur mass extinctions), and Grade 3 (scientific investigation of living systems). A total of 30 elementary schools (N = 2,870 students) were randomized to a treatment or control condition. In the treatment condition (i.e., full spiral curriculum), students participated in content literacy lessons from Grades 1 to 3 during the school year and wide reading of thematically related informational texts in the summer following Grades 1 and 2. In the control condition (i.e., partial spiral curriculum), students participated in lessons in only Grade 3. The Grade 3 lessons for both conditions were implemented online during the COVID-19 pandemic school year. Results reveal that treatment students outperformed control students on science vocabulary knowledge across all three grades. Furthermore, intent-to-treat analyses revealed positive transfer effects on Grade 3 science reading (ES = .14), domain-general reading comprehension (ES = .11), and mathematics achievement (ES = .12). Treatment impacts were sustained at 14-month follow-up on Grade 4 reading comprehension (ES = .12) and mathematics achievement (ES = .16). Findings indicate that a content literacy intervention that spirals topics and vocabulary across grades can improve students' long-term academic achievement outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A Readability Study of Carpal Tunnel Release in 2023.

BACKGROUND: The National Institutes of Health (NIH) and the American Medical Association (AMA) recommend a sixth-grade reading level for patient-directed content. This study aims to quantitatively evaluate the readability of online information sources related to carpal tunnel surgery using established readability indices. METHODS: Web searches for "carpal tunnel release" and "carpal tunnel decompression surgery" queries were performed using Google, and the first 20 websites were identified per query. WebFX online software tools were utilized to determine readability. Indices included Flesch Kincaid Reading Ease, Flesch Kincaid Grade Level, Coleman Liau Index, Automated Readability Index, Gunning Fog Score, and the Simple Measure of Gobbledygook Index. Health-specific clickthrough rate (CTR) data were used in order to select the first 20 search engine results page from each query. RESULTS: "Carpal tunnel release" had a mean readability of 8.46, and "carpal tunnel decompression surgery" had a mean readability of 8.70. The range of mean readability scores among the indices used for both search queries was 6.17 to 14.0. The total mean readability for carpal tunnel surgery information was found to be 8.58. This corresponds to approximately a ninth-grade reading level in the United States. CONCLUSION: The average readability of carpal tunnel surgery online content is three grade levels above the recommended sixth-grade level for patient-directed materials. This discrepancy indicates that existing online materials related to carpal tunnel surgery are more difficult to understand than the standards set by NIH and AMA.

Orgasm Consistency in Mixed-Gender Couples: Actor, Partner, and Discrepancy Effects from Dyadic Response Surface Analysis.

The potential link between orgasm consistency (i.e., the percentage of time an individual experiences orgasm during sexual interactions with a partner) and sexual satisfaction in mixed-gender sexual relationships remains underexamined in the literature. We combined two dyadic samples (N = 725 couples) and utilized Dyadic Response Surface Analysis (DRSA) to examine how both partners' orgasm consistency and their discrepancy of orgasm consistency predict both partners' sexual satisfaction. We found that partners' discrepancy in orgasm consistency was not uniquely connected to higher sexual satisfaction for either women or men; rather, the overall consistency of orgasm was connected to better sexual satisfaction for both partners. In addition, there was some evidence tentatively suggesting that men were more likely than women to report lower sexual satisfaction if his partner was orgasming more consistently than he was, as opposed to her reporting lower sexual satisfaction from him orgasming more consistently than she was; though this appears to be a rare scenario as only 5.9% of couples had women who orgasmed more consistently than men. This study may assist educators and clinicians as they help couples consider the sexual scripts surrounding orgasm consistency, and how they can attend to each others' desires in a way that maximizes sexual satisfaction for both partners.

In symptomatic adults undergoing high-resolution manometry, long-term opioid use was linked to esophageal dysmotility.

SOURCE CITATION: Niu C, Zhang J, Bapaye J, et al. Systematic review with meta-analysis: chronic opioid use is associated with esophageal dysmotility in symptomatic patients. Am J Gastroenterol. 18 Aug 2023. [Epub ahead of print]. 37463432.

A Video Intervention to Improve Patient Understanding of Tumor Genomic Testing in Patients with Cancer.

Background: Tumor genomic testing (TGT) has become standard-of-care for most patients with advanced/metastatic cancer. Despite established guidelines, patient education prior to TGT is variable or frequently omitted. The purpose of this study was to evaluate the impact of a concise (3-4 minute) video for patient education prior to TGT. Methods: Based on a quality improvement cycle, an animated video was created to be applicable to any cancer type, incorporating culturally diverse images, available in English and Spanish. Patients undergoing standard-of care TGT were enrolled at a tertiary academic institution and completed validated survey instruments immediately prior to video viewing (T1) and immediately post-viewing (T2). Instruments included: 1) 10-question objective genomic knowledge/understanding; 2) 10-question video message-specific knowledge/recall; 3) 11-question Trust in Physician/Provider; 4) attitudes regarding TGT. The primary objective was change in outcomes from before to after the video was assessed with Wilcoxon signed rank test. Results: From April 2022 to May 2023, a total of 150 participants were enrolled (MBC n=53, LC n=38, OC n=59). For the primary endpoint, there was a significant increase in video message-specific knowledge (median 10 point increase; p<0.0001) with no significant change in genomic knowledge/understanding (p=0.89) or Trust in Physician/Provider (p=0.59). Results for five questions significantly improved, including the likelihood of TGT impact on treatment decision, incidental germline findings, and cost of testing. Improvement in video message-specific knowledge was consistent across demographic groups, including age, income, and education. Individuals with less educational attainment had had greater improvement from before to after video viewing. Conclusions: A concise, 3-4 minute, broadly applicable video incorporating culturally diverse images administered prior to TGT significantly improved video message-specific knowledge across all demographic groups. This resource is publicly available at http://www.tumor-testing.com, with a goal to efficiently educate and empower patients regarding TGT while addressing guidelines within the flow of clinical practice. Clinical Trial Registration: ClinicalTrials.gov NCT05215769.

The emerging role of digital health in the management of asthma.

The most common reasons seen for lack of asthma control include misconceptions about disease control, low controller treatment adherence, poor inhaler technique, and the resulting underuse of controllers and overuse of short-acting beta2 agonists (SABAs). Narrowing these care gaps may be achieved through well-designed patient education that considers the patient's motivation, beliefs, and capabilities regarding their asthma and its management and empowers the patient to become an active participant in treatment decisions. Digital health technologies (DHTs) and digital therapeutic (DT) devices provide new opportunities to monitor treatment behaviors, improve communication between healthcare providers and patients, and generate data that inform educational interactions. DHT and DT have been proven effective in enhancing patient self-management in other chronic conditions, particularly diabetes. Accelerated integration of DHT and DT into the management of asthma patients is facilitated by the use of digital inhalers that employ sensor technology ("smart" inhalers). These devices efficiently provide real-time feedback on controller adherence, SABA use, and inhaler technique that have the strong potential to optimize asthma control.

Levothyroxine Prescription Error: A Case Report.

Levothyroxine (LT) is the synthetic form of thyroxine (T4), a thyroid hormone analog used to treat hypothyroidism. LT overdose rarely results in severely poor outcomes. General guidelines for treating exogenous thyrotoxicosis depend on the severity of symptoms. There is no standardized protocol; however, drug discontinuation, beta-blockers (specifically propranolol), and cholestyramine effectively manage overdose when needed, with most cases resolving independently without medical intervention.  Here, we present the case of a 26-year-old female with a history of supraventricular tachycardia, anxiety, depression, and Hashimoto thyroiditis who was accidentally overprescribed LT (300 mcg for one and a half months) that resulted in symptoms of lethargy, tremors, body temperature dysregulation, orthostatic hypotension, and diarrhea. This case, with limited evidence, suggests that excessive LT exacerbated the patient's underlying psychiatric symptoms, encouraging suicidal ideation.

Heart Break or Headache: A Case Report of Sumatriptan-Induced Takotsubo Syndrome.

Takotsubo syndrome (TS) describes a transient type of dilated cardiomyopathy that mimics acute coronary syndrome (ACS) on initial presentation. Classic TS presents with marked dilation and ballooning of the left ventricular apex with hyperdynamic basal segments. The most frequent etiology is from emotional and stressful triggers; recently, evidence suggests neurologic and psychiatric involvement. There are increasing reports of TS occurring secondary to migraine abortives. We describe a unique case of TS in a woman after taking sumatriptan to abort her headache.

Lower Back Pain Imaging: A Readability Analysis.

PURPOSE: The internet provides access to a myriad of educational health-related resources which are an invaluable source of information for patients. Lower back pain is a common complaint that is discussed extensively online. In this article, we aim to determine if the most commonly accessed articles about lower back pain imaging use language that can be understood by most patients. According to the American Medical Association (AMA) and National Institute of Health (NIH), this corresponds to a sixth-grade reading level. METHODS: Online searches were conducted from the most commonly used search engine, Google, to assess the present state of readability on radiograph imaging for LBP. Then the top 20 populated URL links from each search were utilized based on "health & fitness" search trends and click-through rates (CTRs). The readability of various websites was evaluated with WebFX online software that analyzed the unique websites' text when put into reader view on Firefox web browser version 116.0.3 (64-bit). Evaluation occurred via five common readability indices: the Automated Readability Index (ARI), the Coleman Liau Index (CLI), the SMOG index, the Gunning Fog Score Index (GFSI), and the Flesch Kincaid Grade Level Index (FKGLI). In addition, the Flesch Kincaid Reading Ease Index (FKREI) was also used but was excluded from the calculation due to its measuring scale outside of US grade levels. The number of samples was analyzed via health and fitness-specific CTR from an open-access database from July 2022 to July 2023. This was used to calculate the number of persons clicking and visiting positional URLs (first URL to the 20th URL) from each unique keyword search and the rational criteria for selecting the first 20 websites for each query. RESULTS: Online material that included LBP imaging information was calculated to have an overall readability score of 10.745 out of the 23 websites obtained from unique searches. The range was a mean readability score of 8 to 14. Notably, 17 websites were excluded from a total of 40 websites due to duplication of the same data (URLs that resulted from both unique searches) and accessibility requiring payment (specifically, an UpToDate link). A readability score of 10.745 refers to an 11th-grade reading level. That is to say, the most commonly visited sites on Google that contain information about lower back pain imaging are, on average, five grade levels higher than the sixth-grade reading level recommended by the AMA and the NIH. CONCLUSIONS: Most internet content regarding lower back pain imaging is written at a reading level that is above the recommended limit defined by the AMA and NIH. To improve education about lower back pain imaging and the patient-physician relationship, we recommend guiding patients to online material that contains a reading level at the sixth-grade level as suggested by the AMA and NIH.

Literature-Based Discovery to Elucidate the Biological Links between Resistant Hypertension and COVID-19.

Multiple studies have reported new or exacerbated persistent or resistant hypertension in patients previously infected with COVID-19. We used literature-based discovery to identify and prioritize multi-scalar explanatory biology that relates resistant hypertension to COVID-19. Cross-domain text mining of 33+ million PubMed articles within a comprehensive knowledge graph was performed using SemNet 2.0. Unsupervised rank aggregation determined which concepts were most relevant utilizing the normalized HeteSim score. A series of simulations identified concepts directly related to COVID-19 and resistant hypertension or connected via one of three renin-angiotensin-aldosterone system hub nodes (mineralocorticoid receptor, epithelial sodium channel, angiotensin I receptor). The top-ranking concepts relating COVID-19 to resistant hypertension included: cGMP-dependent protein kinase II, MAP3K1, haspin, ral guanine nucleotide exchange factor, N-(3-Oxododecanoyl)-L-homoserine lactone, aspartic endopeptidases, metabotropic glutamate receptors, choline-phosphate cytidylyltransferase, protein tyrosine phosphatase, tat genes, MAP3K10, uridine kinase, dicer enzyme, CMD1B, USP17L2, FLNA, exportin 5, somatotropin releasing hormone, beta-melanocyte stimulating hormone, pegylated leptin, beta-lipoprotein, corticotropin, growth hormone-releasing peptide 2, pro-opiomelanocortin, alpha-melanocyte stimulating hormone, prolactin, thyroid hormone, poly-beta-hydroxybutyrate depolymerase, CR 1392, BCR-ABL fusion gene, high density lipoprotein sphingomyelin, pregnancy-associated murine protein 1, recQ4 helicase, immunoglobulin heavy chain variable domain, aglycotransferrin, host cell factor C1, ATP6V0D1, imipramine demethylase, TRIM40, H3C2 gene, COL1A1+COL1A2 gene, QARS gene, VPS54, TPM2, MPST, EXOSC2, ribosomal protein S10, TAP-144, gonadotropins, human gonadotropin releasing hormone 1, beta-lipotropin, octreotide, salmon calcitonin, des-n-octanoyl ghrelin, liraglutide, gastrins. Concepts were mapped to six physiological themes: altered endocrine function, 23.1%; inflammation or cytokine storm, 21.3%; lipid metabolism and atherosclerosis, 17.6%; sympathetic input to blood pressure regulation, 16.7%; altered entry of COVID-19 virus, 14.8%; and unknown, 6.5%.

Ollier Disease: A Case Report and Review of Treatment Options.

Ollier disease is a rare skeletal dysplasia characterized by the formation of multiple enchondromas (enchondromatosis), typically in the long bones of the extremities. These tumors are benign but can become complicated by the development of pathologic fractures, limb deformity, and malignant transformation to chondrosarcoma. Ollier disease has a highly variable presentation and is associated with a range of presenting findings; however, the most common presentation is a pathologic fracture. Surgical options include curettage and grafting of the enchondromas and, when displaced, fracture reduction and fixation. Of note, these fractures will heal without surgery. Regardless, all patients must be routinely monitored with yearly radiographs in order to detect malignant transformation as early as possible.  In this report, we describe the case of an 11-year-old female who presented to her physician with pain and swelling of her right ring and small fingers after playing in a swimming pool with no obvious mechanism of trauma. A routine, plain radiographic evaluation of her hand revealed the presence of multiple enchondromatosis. We hope to use this case to highlight the surgical management options for young patients with Ollier disease and discuss circumstances in which surgical management may not be indicated.

Not Who You Are, But Who You Are With: Re-examining Women's Less Satisfying Sexual Debuts.

Gender differences in appraisals of first intercourse are among the largest in sexuality research, with women indicating less satisfying "sexual debuts" than men. Dispositional or "actor-level" explanations for this gender gap are pervasive, yet research has largely examined heterosexual debuts in which actor gender and partner gender are confounded. We assessed whether women's less satisfying sexual debuts are better explained by actor gender or partner gender, comparing experiences of women who debuted with men (WDM) with those of men and women who debuted with women (MDW, WDW). Retrospective accounts of sexual debut were collected from 3033 adults. At first intercourse, we found that WDW had equal physical and emotional satisfaction to MDW, and more satisfaction than WDM, suggesting satisfaction gaps owing to partner gender, not actor gender. This pattern did not extend to a comparison event (first masturbation), where WDW and WDM had similar satisfaction, but less satisfaction than MDW, suggesting an actor gender gap. To identify sources of satisfaction gaps, we probed for corresponding differences in the circumstances of sexual debut. Sexual circumstances were more strongly implicated than nonsexual ones, with relative deprivation of glans stimulation explaining relative dissatisfaction at first intercourse, but not first masturbation, and orgasm explaining it at both. Findings challenge the view that the satisfaction gap at first intercourse reflects an inherent difference between genders. Indeed, they demonstrate similarities when partner gender does not differ and suggest strategies for ensuring equal sexual satisfaction-and equal sexual rights realization-at (hetero) sexual debut.

MSC.sensor: Capturing cancer cell interactions with stroma for functional profiling.

Mesenchymal stromal cells (MSCs) contribute to the microenvironment regulating normal and malignant hematopoiesis, and thus may support subpopulations of cancer cells to escape therapeutic pressure. Here, we engineered bone marrow MSCs to express a synthetic CD19-sensor receptor to detect and display interacting primary CD19+ leukemia cells in coculture. This implementation provides a versatile platform facilitating ex vivo drug response profiling of primary CD19+ leukemia cells in coculture with high-sensitivity and scalability.