Leading causes of death in Vietnamese Americans: An ecological study based on national death records from 2005-2020.

BACKGROUND: Disaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020. METHODS: Decedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately. FINDINGS: We identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms. CONCLUSIONS AND RELEVANCE: While VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures.

Consensus-based ethical best practices for performing educational point-of-care ultrasonography in the emergency department.

Objectives: There is no standardized protocol for performing educational point-of-care ultrasonography (POCUS) that addresses patient-centered ethical issues such as obtaining informed consent. This study sought to define principles for ethical application of educational POCUS and develop consensus-based best practice guidance. Methods: A questionnaire was developed by a trained ethicist after literature review with the help of a medical librarian. A diverse panel including experts in medical education, law, and bioethics; medical trainees; and individuals with no medical background was convened. The panel voted on their level of agreement with ethical principles and degree of appropriateness of behaviors in three rounds of a modified Delphi process. A high level of agreement was defined as 80% or greater consensus. Results: Panelists voted on 38 total items: 15 related to the patient consent and selection process, eight related to practices while performing educational POCUS, and 15 scenarios involving POCUS application. A high level of agreement was achieved for 13 items related to patient consent and selection, eight items related to performance practices, and 10 scenarios of POCUS application. Conclusions: Based on expert consensus, ethical best practices include obtaining informed consent before performing educational POCUS, allowing patients to decline educational POCUS, informing patients the examination is not intended to be a part of their medical evaluation and is not billed, using appropriate draping techniques, maintaining a professional environment, and disclosing incidental findings in coordination with the primary team caring for the patient. These practices could be implemented at institutions to encourage ethical use of educational POCUS when training physicians, fellows, residents, and medical students.

Prevalence of Gastric Precursor Lesions in Countries With Differential Gastric Cancer Burden: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: The prevalence of precursor lesions for gastric cancer (GC) and the differential burden between countries of varying GC risk is not well-understood. We conducted a systematic review and meta-analysis to estimate the global prevalence of precursor lesions. METHODS: We estimated the prevalence of atrophic gastritis (AG), gastric intestinal metaplasia (IM), and dysplasia in regions with low, medium, and high GC incidence. Because IM is an advanced manifestation of AG, we assessed the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. Prevalence was sub-stratified by Helicobacter pylori infection, symptomatology, and period (<2000, 2000-2010, and >2010). RESULTS: Among the 582 articles that underwent full-text review, 166 studies met inclusion criteria. The global prevalence estimates of AG, IM, and dysplasia were 25.4%, 16.2%, and 2.0%, respectively, on the basis of 126 studies that reported the prevalence of less advanced precursors, regardless of the presence of more advanced lesions. The prevalence of all precursor lesions was higher in high and medium compared with low GC incidence countries (P < .01). Prevalence of AG and IM was significantly higher among H pylori-infected individuals (P < .01) but not statistically different between symptomatic and asymptomatic individuals (P > .17). All precursors demonstrated a secular decrease in prevalence over time. CONCLUSIONS: Gastric precursor lesions have differences in prevalence in regions with differential GC incidence and are associated with H pylori infection. Because of the substantial prevalence of precursor lesions in both symptomatic and asymptomatic individuals, symptomatic evaluation may not be sufficient to identify individuals at risk. These estimates provide important insights for tailoring GC prevention strategies.

Risk of Gastric Adenocarcinoma in a Multiethnic Population Undergoing Routine Care: An Electronic Health Records Cohort Study.

BACKGROUND: Gastric adenocarcinoma (GAC) is often diagnosed at advanced stages and portends a poor prognosis. We hypothesized that electronic health records (EHR) could be leveraged to identify individuals at highest risk for GAC from the population seeking routine care. METHODS: This was a retrospective cohort study, with endpoint of GAC incidence as ascertained through linkage to an institutional tumor registry. We utilized 2010 to 2020 data from the Palo Alto Medical Foundation, a large multispecialty practice serving Northern California. The analytic cohort comprised individuals ages 40-75 receiving regular ambulatory care. Variables collected included demographic, medical, pharmaceutical, social, and familial data. Electronic phenotyping was based on rule-based methods. RESULTS: The cohort comprised 316,044 individuals and approximately 2 million person-years (p-y) of observation. 157 incident GACs occurred (incidence 7.9 per 100,000 p-y), of which 102 were non-cardia GACs (incidence 5.1 per 100,000 p-y). In multivariable analysis, male sex [HR: 2.2, 95% confidence interval (CI): 1.6-3.1], older age, Asian race (HR: 2.5, 95% CI: 1.7-3.7), Hispanic ethnicity (HR: 1.9, 95% CI: 1.1-3.3), atrophic gastritis (HR: 4.6, 95% CI: 2.2-9.3), and anemia (HR: 1.9, 95% CI: 1.3-2.6) were associated with GAC risk; use of NSAID was inversely associated (HR: 0.3, 95% CI: 0.2-0.5). Older age, Asian race, Hispanic ethnicity, atrophic gastritis, and anemia were associated with non-cardia GAC. CONCLUSIONS: Routine EHR data can stratify the general population for GAC risk. IMPACT: Such methods may help triage populations for targeted screening efforts, such as upper endoscopy.

Variability in Interpretation of Echocardiographic Signs of Tamponade: A Survey of Emergency Physician Sonographers.

BACKGROUND: Cardiac tamponade is associated with high mortality, and making the diagnosis is a core skill of emergency physicians. Proper diagnosis relies on specific clinical and echocardiographic findings. It is not known whether expert sonographers consistently recognize echocardiographic signs of tamponade. OBJECTIVES: To assess whether expert sonographers agree on echocardiographic signs of tamponade. METHODS: A 20-question survey consisting of 18 cine loops and 2 still images was distributed to the Academy of Emergency Ultrasound Section of the Society for Academic Emergency Medicine. Respondents answered "yes" or "no" to whether there was echocardiographic evidence of tamponade. Subgroup analyses of demographics and echocardiographic views were reported. The data were analyzed using Krippendorff's alpha (α) to assess interrater reliability (IRR) between respondents. RESULTS: Eighty-four physicians responded and 56 completed the survey. All partial and completed surveys were analyzed. The overall IRR was poor (α = 0.60, 95% confidence interval [CI] 0.44-0.76). Residency graduation within 5 years (α = 0.66, 95% CI 0.5-0.8) was associated with higher IRR compared with those > 5 years (α = 0.53, 95% CI 0.37-0.69). The highest IRR was observed when images of mitral valve inflow pulse-wave Doppler (α = 0.81, CI 0.70-0.92) were used and the poorest IRR was on images from the parasternal short view (α = 0.28, 95% CI 0.05-0.49). CONCLUSION: There was poor agreement among expert emergency medicine sonographers in identifying echocardiographic signs of cardiac tamponade from a single cine loop or clip without clinical context. Further investigation is warranted to understand differences in recognition of clinical tamponade.

The association between local area immigrant fraction and prevalence of cardiovascular diseases in the United States: an observational study.

Background: Local area immigrant fraction is strongly and positively correlated with local life expectancy in the United States. The aim of the study was to determine the relationship between local area immigrant fraction and local prevalence of coronary heart disease (CHD) and stroke. Methods: Cross-sectional study design, with ZIP code as the unit of observation. Demographic data was obtained from the American Community Survey, and linked to indicators of health access (e.g., insurance, annual check-ups, cholesterol screening), obesity, behavior (smoking, exercise), and cardiovascular outcomes data from the 2020 Population Level Analysis and Community Estimates. Multivariable regression and path analyses were used to assess both direct and indirect relationships among variables. Findings: CHD prevalence was lower in the second (3.9% relative difference, 95% CI: 3.1-4.5%), third (6.5%, 95% CI: 5.8-7.1%), and fourth (14.8%, 95% CI: 14.1-15.8%) quartiles of immigrant fraction compared to the lowest (p-trend <0.001). These effects remained robust in multivariable analysis following adjustment for indicators of access, obesity, and behavioral variables (p-trend <0.0001). For stroke, only the highest quartile demonstrated a significant difference in prevalence (2.1%, 95% CI: 1.2-3.0% with full adjustment). In CHD path analysis, ∼45% of the association of immigrant fraction was direct, and ∼55% was mediated through lower prevalence of deleterious behaviors (e.g., smoking). In stroke path analysis, the effect was entirely mediated through indirect effects. Interpretation: In the United States, ZIP codes with higher immigrant fractions have lower prevalence of cardiovascular diseases. These associations are partially mediated through differences in health behaviors at the community level. Funding: NIH (K08CA252635, P30AG0059304, K24HL150476), Stanford University, Rutgers University.

A spatially mapped gene expression signature for intestinal stem-like cells identifies high-risk precursors of gastric cancer.

Objective: Gastric intestinal metaplasia (GIM) is a precancerous lesion that increases gastric cancer (GC) risk. The Operative Link on GIM (OLGIM) is a combined clinical-histopathologic system to risk-stratify patients with GIM. The identification of molecular biomarkers that are indicators for advanced OLGIM lesions may improve cancer prevention efforts. Methods: This study was based on clinical and genomic data from four cohorts: 1) GAPS, a GIM cohort with detailed OLGIM severity scoring (N=303 samples); 2) the Cancer Genome Atlas (N=198); 3) a collation of in-house and publicly available scRNA-seq data (N=40), and 4) a spatial validation cohort (N=5) consisting of annotated histology slides of patients with either GC or advanced GIM. We used a multi-omics pipeline to identify, validate and sequentially parse a highly-refined signature of 26 genes which characterize high-risk GIM. Results: Using standard RNA-seq, we analyzed two separate, non-overlapping discovery (N=88) and validation (N=215) sets of GIM. In the discovery phase, we identified 105 upregulated genes specific for high-risk GIM (defined as OLGIM III-IV), of which 100 genes were independently confirmed in the validation set. Spatial transcriptomic profiling revealed 36 of these 100 genes to be expressed in metaplastic foci in GIM. Comparison with bulk GC sequencing data revealed 26 of these genes to be expressed in intestinal-type GC. Single-cell profiling resolved the 26-gene signature to both mature intestinal lineages (goblet cells, enterocytes) and immature intestinal lineages (stem-like cells). A subset of these genes was further validated using single-molecule multiplex fluorescence in situ hybridization. We found certain genes (TFF3 and ANPEP) to mark differentiated intestinal lineages, whereas others (OLFM4 and CPS1) localized to immature cells in the isthmic/crypt region of metaplastic glands, consistent with the findings from scRNAseq analysis. Conclusions: using an integrated multi-omics approach, we identified a novel 26-gene expression signature for high-OLGIM precursors at increased risk for GC. We found this signature localizes to aberrant intestinal stem-like cells within the metaplastic microenvironment. These findings hold important translational significance for future prevention and early detection efforts.

Software Application Profile: dynamicLM-a tool for performing dynamic risk prediction using a landmark supermodel for survival data under competing risks.

MOTIVATION: Providing a dynamic assessment of prognosis is essential for improved personalized medicine. The landmark model for survival data provides a potentially powerful solution to the dynamic prediction of disease progression. However, a general framework and a flexible implementation of the model that incorporates various outcomes, such as competing events, have been lacking. We present an R package, dynamicLM, a user-friendly tool for the landmark model for the dynamic prediction of survival data under competing risks, which includes various functions for data preparation, model development, prediction and evaluation of predictive performance. IMPLEMENTATION: dynamicLM as an R package. GENERAL FEATURES: The package includes options for incorporating time-varying covariates, capturing time-dependent effects of predictors and fitting a cause-specific landmark model for time-to-event data with or without competing risks. Tools for evaluating the prediction performance include time-dependent area under the ROC curve, Brier Score and calibration. AVAILABILITY: Available on GitHub [https://github.com/thehanlab/dynamicLM].

Cultural Humility Curriculum to Address Healthcare Disparities for Emergency Medicine Residents.

INTRODUCTION: Emergency medicine (EM) residency programs have variable approaches to educating residents on recognizing and managing healthcare disparities. We hypothesized that our curriculum with resident-presented lectures would increase residents' sense of cultural humility and ability to identify vulnerable populations. METHODS: At a single-site, four-year EM residency program with 16 residents per year, we designed a curriculum intervention from 2019-2021 where all second-year residents selected one healthcare disparity topic and gave a 15-minute presentation overviewing the disparity, describing local resources, and facilitating a group discussion. We conducted a prospective observational study to assess the impact of the curriculum by electronically surveying all current residents before and after the curriculum intervention. We measured attitudes on cultural humility and ability to identify healthcare disparities among a variety of patient characteristics (race, gender, weight, insurance, sexual orientation, language, ability, etc). Statistical comparisons of mean responses were calculated using the Mann-Whitney U test for ordinal data. RESULTS: A total of 32 residents gave presentations that covered a broad range of vulnerable patient populations including those that identify as Black, migrant farm workers, transgender, and deaf. The overall survey response was 38/64 (59.4%) pre-intervention and 43/64 (67.2%) post-intervention. Improvements were seen in resident self-reported cultural humility as measured by their responsibility to learn (mean responses of 4.73 vs 4.17; P < 0.001) and responsibility to be aware of different cultures (mean responses of 4.89 vs 4.42; P < 0.001). Residents reported an increased awareness that patients are treated differently in the healthcare system based on their race (P < 0.001) and gender (P < 0.001). All other domains queried, although not statistically significant, demonstrated a similar trend. CONCLUSION: This study demonstrates increased resident willingness to engage in cultural humility and the feasibility of resident near-peer teaching on a breadth of vulnerable patient populations seen in their clinical environment. Future studies may query the impact this curriculum has on resident clinical decision-making.

Controlling Gastric Cancer in a World of Heterogeneous Risk.

Gastric cancer (GC) is a leading cause of global mortality but also a cancer whose footprint is highly unequal. This review aims to define global disease epidemiology, critically appraise strategies of prevention and disease attenuation, and assess how these strategies could be applied to improve outcomes from GC in a world of variable risk and disease burden. Strategies of primary prevention focus on improving the detection and eradication of the main environmental risk factor, Helicobacter pylori. In certain countries of high incidence, endoscopic or radiographic screening of the asymptomatic general population has been adopted as a means of secondary prevention. By contrast, identification and targeted surveillance of individuals with precancerous lesions (such as intestinal metaplasia) is being increasingly embraced in nations of low incidence. This review also highlights existing knowledge gaps in GC prevention as well as the role of emerging technologies for early detection and risk stratification.

A Brief Overview of Emerging Vaccine Technologies for Pandemic Preparedness.

Over the past two decades, pandemic preparedness has proven to be critical to health, national, and economic security. Now, countries are investing billions of dollars in various pandemic preparedness tools, such as vaccines and broad-spectrum medical countermeasures (MCM), to address the threats arising from outbreaks. These tools not only offer protection against naturally occurring and accidental biological incidents but can also help provide some protection against deliberate biological attacks. Furthermore, pandemic preparedness has substantial economic implications for both the public and private sectors because of its connection with the biotechnology industry, an important component of the worldwide economy. With so many aspects of pandemic preparedness tied to public health, national security, and economic competition, understanding the key technology and policy trends of the major country stakeholders in this space provides valuable insights into pandemic preparedness gaps and ways of addressing them. This study provides a brief characterization of the trends and strategic implications associated with specific aspects of pandemic preparedness in the United States, China, and Russia. The authors discuss both technical and policy aspects of vaccine concepts and technologies, broad-spectrum MCM, and immunization facilitation.

Low rates of structured advance care planning documentation in electronic health records: results of a single-center observational study.

BACKGROUND: Proper advance care planning (ACP) documentation both improves patient care and is increasingly seen as a marker of high quality by governmental payers. The transition of most medical documentation to electronic health records (EHR) allows for ACP documents to be rapidly disseminated across diverse ambulatory practice settings. At the same time, the complexity and heterogeneity of the EHR, as well as the multiple potential storage locations for documentation, may lead to confusion and inaccessibility. There has been movement to promote structured ACP (S-ACP) documentation within the EHR. METHODS: We performed a retrospective cohort study at a single, large university medical center in California to analyze rates of S-ACP documentation. S-ACP was defined as ACP documentation contained in standardized locations, auditable, and not in free-text format. The analytic cohort composed of all patients 65 and older with at least one ambulatory encounter at Stanford Health Care between 2012 and 2020, and without concurrent hospice care. We then analyzed clinic-level, provider-level, insurance, and temporal factors associated with S-ACP documentation rate. RESULTS: Of 187,316 unique outpatient encounters between 2012 and 2020, only 7,902 (4.2%) contained S-ACP documentation in the EHR. The most common methods of S-ACP documentation were through problem list diagnoses (3,802; 40.3%) and scanned documents (3,791; 40.0%). At the clinic level, marked variability in S-ACP documentation was observed, with Senior Care (46.6%) and Palliative Care (25.0%) demonstrating highest rates. There was a temporal trend toward increased S-ACP documentation rate (p < 0.001). CONCLUSION: This retrospective, single-center study reveals a low rate of S-ACP documentation irrespective of clinic and specialty. While S-ACP documentation rate should not be construed as a proxy for ACP documentation rate, it nonetheless serves as an important quality metric which may be reported to payers. This study highlights the need to both centralize and standardize reporting of ACP documentation in complex EHR systems.

Leading causes of death in Asian Indians in the United States (2005-2017).

OBJECTIVE: Asian Indians are among the fastest growing United States (US) ethnic subgroups. We characterized mortality trends for leading causes of death among foreign-born and US-born Asian Indians in the US between 2005-2017. STUDY DESIGN AND SETTING: Using US standardized death certificate data, we examined leading causes of death in 73,470 Asian Indians and 20,496,189 non-Hispanic whites (NHWs) across age, gender, and nativity. For each cause, we report age-standardized mortality rates (AMR), longitudinal trends, and absolute percent change (APC). RESULTS: We found that Asian Indians' leading causes of death were heart disease (28% mortality males; 24% females) and cancer (18% males; 22% females). Foreign-born Asian Indians had higher all-cause AMR compared to US-born (AMR 271 foreign-born, CI 263-280; 175.8 US-born, CI 140-221; p<0.05), while Asian Indian all-cause AMR was lower than that of NHWs (AMR 271 Indian, CI 263-278; 754.4 NHW, CI 753.3-755.5; p<0.05). All-cause AMR increased for foreign-born Asian Indians over time, while decreasing for US-born Asian Indians and NHWs. CONCLUSIONS: Foreign-born Asian Indians were 2.2 times more likely to die of heart disease and 1.6 times more likely to die of cancer. Asian Indian male AMR was 49% greater than female on average, although AMR was consistently lower for Asian Indians when compared to NHWs.

Catching Up with the World: Pepsinogen Screening for Gastric Cancer in the United States.

Gastric cancer remains a deadly cancer with poor outcomes in the United States. There is a need for screening strategies for gastric cancer in the U.S. population. With progressive Helicobacter pylori-mediated inflammation of the gastric mucosa, pepsinogen I levels decrease and the pepsinogen I/II ratio decreases. Pepsinogen test positivity (PG+) has been evaluated as a promising screening test among Asian and European populations; however, its utility in multiethnic U.S. populations is poorly described. In this case-control study nested within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, In and colleagues evaluate the discrimination of PG+ in serum collected from individuals prior to the development of gastric cancer. The authors find that PG+ individuals were at nearly 10-fold increased risk for developing gastric cancer, and this effect remained robust after adjusting for Helicobacter pylori status, family history, education, smoking, and obesity. In subgroup analysis, the predictive ability of the test was particularly robust for noncardia gastric cancers, and nonpredictive of cardia gastric cancers. Serum pepsinogen testing holds promise as a noninvasive screening strategy to triage individuals at heightened risk for gastric cancer, and may help to improve early diagnosis in the United States. See related article by In et al., p. 1426.

A Comparison of Logistic Regression Against Machine Learning Algorithms for Gastric Cancer Risk Prediction Within Real-World Clinical Data Streams.

PURPOSE: Noncardia gastric cancer (NCGC) is a leading cause of global cancer mortality, and is often diagnosed at advanced stages. Development of NCGC risk models within electronic health records (EHR) may allow for improved cancer prevention. There has been much recent interest in use of machine learning (ML) for cancer prediction, but few studies comparing ML with classical statistical models for NCGC risk prediction. METHODS: We trained models using logistic regression (LR) and four commonly used ML algorithms to predict NCGC from age-/sex-matched controls in two EHR systems: Stanford University and the University of Washington (UW). The LR model contained well-established NCGC risk factors (intestinal metaplasia histology, prior Helicobacter pylori infection, race, ethnicity, nativity status, smoking history, anemia), whereas ML models agnostically selected variables from the EHR. Models were developed and internally validated in the Stanford data, and externally validated in the UW data. Hyperparameter tuning of models was achieved using cross-validation. Model performance was compared by accuracy, sensitivity, and specificity. RESULTS: In internal validation, LR performed with comparable accuracy (0.732; 95% CI, 0.698 to 0.764), sensitivity (0.697; 95% CI, 0.647 to 0.744), and specificity (0.767; 95% CI, 0.720 to 0.809) to penalized lasso, support vector machine, K-nearest neighbor, and random forest models. In external validation, LR continued to demonstrate high accuracy, sensitivity, and specificity. Although K-nearest neighbor demonstrated higher accuracy and specificity, this was offset by significantly lower sensitivity. No ML model consistently outperformed LR across evaluation criteria. CONCLUSION: Drawing data from two independent EHRs, we find LR on the basis of established risk factors demonstrated comparable performance to optimized ML algorithms. This study demonstrates that classical models built on robust, hand-chosen predictor variables may not be inferior to data-driven models for NCGC risk prediction.

The Gastric Cancer Registry: A Genomic Translational Resource for Multidisciplinary Research in Gastric Cancer.

BACKGROUND: Gastric cancer is a leading cause of cancer morbidity and mortality. Developing information systems which integrate clinical and genomic data may accelerate discoveries to improve cancer prevention, detection, and treatment. To support translational research in gastric cancer, we developed the Gastric Cancer Registry (GCR), a North American repository of clinical and cancer genomics data. METHODS: Participants self-enrolled online. Entry criteria into the GCR included the following: (i) diagnosis of gastric cancer, (ii) history of gastric cancer in a first- or second-degree relative, or (iii) known germline mutation in the gene CDH1. Participants provided demographic and clinical information through a detailed survey. Some participants provided specimens of saliva and tumor samples. Tumor samples underwent exome sequencing, whole-genome sequencing, and transcriptome sequencing. RESULTS: From 2011 to 2021, 567 individuals registered and returned the clinical questionnaire. For this cohort 65% had a personal history of gastric cancer, 36% reported a family history of gastric cancer, and 14% had a germline CDH1 mutation. 89 patients with gastric cancer provided tumor samples. For the initial study, 41 tumors were sequenced using next-generation sequencing. The data was analyzed for cancer mutations, copy-number variations, gene expression, microbiome, neoantigens, immune infiltrates, and other features. We developed a searchable, web-based interface (the GCR Genome Explorer) to enable researchers' access to these datasets. CONCLUSIONS: The GCR is a unique, North American gastric cancer registry which integrates clinical and genomic annotation. IMPACT: Available for researchers through an open access, web-based explorer, the GCR Genome Explorer will accelerate collaborative gastric cancer research across the United States and world.

ALTEN: A High-Fidelity Primary Tissue-Engineering Platform to Assess Cellular Responses Ex Vivo.

To fully investigate cellular responses to stimuli and perturbations within tissues, it is essential to replicate the complex molecular interactions within the local microenvironment of cellular niches. Here, the authors introduce Alginate-based tissue engineering (ALTEN), a biomimetic tissue platform that allows ex vivo analysis of explanted tissue biopsies. This method preserves the original characteristics of the source tissue's cellular milieu, allowing multiple and diverse cell types to be maintained over an extended period of time. As a result, ALTEN enables rapid and faithful characterization of perturbations across specific cell types within a tissue. Importantly, using single-cell genomics, this approach provides integrated cellular responses at the resolution of individual cells. ALTEN is a powerful tool for the analysis of cellular responses upon exposure to cytotoxic agents and immunomodulators. Additionally, ALTEN's scalability using automated microfluidic devices for tissue encapsulation and subsequent transport, to enable centralized high-throughput analysis of samples gathered by large-scale multicenter studies, is shown.