The unseen patient: competing priorities between patients and providers when cannabis is used in pregnancy, a qualitative study.

Objectives: This study aimed to explore competing priorities when cannabis is used during pregnancy from the perspective of providers and Black and Latina people. Maternal cannabis use is increasingly common, but patients and providers alike struggle to navigate it. Methods: This pilot used qualitative, constructivist ground theory methods to conduct semi-structured, remote interviews between 16 November 2021, and 7 February 2022 with 7 Black and Latina people who used cannabis during pregnancy, and 10 providers between 15 March 2022, and 6 April 2022, all of who were in Southern California, U.S. Results: We identified three main findings: (1) Providers reported barriers to caregiving and relationship building with patients due to maternal cannabis use stigma, (2) Providers prioritized the fetus despite patients' current health system challenges that drove cannabis use, and (3) Both patients and providers engaged in personal research beyond the healthcare system to better understand maternal cannabis use. Discussion: Our findings indicate that challenges exist between people who use cannabis during pregnancy and providers. Both groups need accurate, sociocultural sensitive information about maternal cannabis use via a harm reduction lens.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Development and Application of a Multidimensional Database for the Detection of Quaternary Ammonium Compounds and Their Phase I Hepatic Metabolites in Humans.

The COVID-19 pandemic has led to significantly increased human exposure to the widely used disinfectants quaternary ammonium compounds (QACs). Xenobiotic metabolism serves a critical role in the clearance of environmental molecules, yet limited data are available on the routes of QAC metabolism or metabolite levels in humans. To address this gap and to advance QAC biomonitoring capabilities, we analyzed 19 commonly used QACs and their phase I metabolites by liquid chromatography-ion mobility-tandem mass spectrometry (LC-IM-MS/MS). In vitro generation of QAC metabolites by human liver microsomes produced a series of oxidized metabolites, with metabolism generally occurring on the alkyl chain group, as supported by MS/MS fragmentation. Discernible trends were observed in the gas-phase IM behavior of QAC metabolites, which, despite their increased mass, displayed smaller collision cross-section (CCS) values than those of their respective parent compounds. We then constructed a multidimensional reference SQLite database consisting of m/z, CCS, retention time (rt), and MS/MS spectra for 19 parent QACs and 81 QAC metabolites. Using this database, we confidently identified 13 parent QACs and 35 metabolites in de-identified human fecal samples. This is the first study to integrate in vitro metabolite biosynthesis with LC-IM-MS/MS for the simultaneous monitoring of parent QACs and their metabolites in humans.

Analysis of demographics and the impact of adjuvant radiotherapy on a nationwide cohort of patients with high-grade spinal meningiomas.

Background: Although typically benign, 5% of spinal meningiomas (SMs) present with higher-grade features (World Health Organization grades 2 and 3). High-grade SMs are poorly studied and the role of adjuvant radiotherapy in their management remains controversial. We hence aimed to study the demographic characteristics of this rare tumor and investigate the outcomes associated with the use of surgery with adjuvant therapy in contrast to surgery alone. Methods: The National Cancer Database was queried for patients with SMs from 2004 to 2017. Basic statistics were used to identify differences between low- and high-grade tumors in terms of baseline characteristics. Surgery with and without adjuvant radiotherapy were compared after (1:1) propensity-score matching. Kaplan-Meier survival analysis was conducted to study overall survival. All analyses were performed on R. Results: A total of 13 184 patients diagnosed with SMs were included, of whom only 5% (n = 669) had high-grade SMs. Patients with high-grade SMs presented at a younger median age (57 years [IQR: 44-68] versus 65 years [54-75]; P < .001) and were more commonly males (33% vs 20%; P < .001). After propensity-score matching, survival analysis revealed similar overall survival outcomes in patients with high-grade SM undergoing both surgery and radiotherapy as compared to those only receiving surgery (P = .19). Conclusions: This study reveals major demographic differences between high- and low-grade SMs. There were no benefits associated with the use of adjuvant radiotherapy. However, due to confounding, overall survival outcomes between patients receiving surgery alone and those receiving surgery with adjuvant radiotherapy are not causally interpretable.

Are We the Problem? A Call to Action for Addressing Institutional Challenges to Engaging Community Partners in Research.

Community-engaged research (CEnR) is a potent tool for addressing health inequities and fostering equitable relationships among communities, researchers, and institutions. CEnR involves collaboration throughout the research process, demonstrating improvements in study recruitment and retention, intervention efficacy, program sustainability, capacity building among partners, and enhanced cultural relevance. Despite the increasing demand for CEnR, institutional policies, particularly human participation protection training (HPP), lag behind, creating institutional barriers to community partnerships. Here, we highlight challenges encountered in our ongoing study, Fostering Opportunities in Research through Messaging and Education (FOR ME), focused on promoting shared decision-making around clinical trial participation among Black women diagnosed with breast cancer. Grounded in CEnR methods, FOR ME has a partnership with a community-based organization (CBO) that addresses the needs of Black women with breast cancer. Our CBO partner attempted to obtain HPP training, which was administratively burdensome and time-consuming. As CEnR becomes more prevalent, academic and research institutions, along with researchers, are faced with a call to action to become more responsive to community partner needs. Accordingly, we present a guide to HPP training for community partners, addressing institutional barriers to community partner participation in research. This guide outlines multiple HPP training pathways for community partners, aiming to minimize institutional barriers and enhance their engagement in research with academic partners.

ERBB3 Overexpression is Enriched in Diverse Patient Populations with Castration-sensitive Prostate Cancer and is Associated with a Unique AR Activity Signature.

PURPOSE: Despite successful clinical management of castration-sensitive prostate cancer (CSPC), the 5-year survival rate for men with castration-resistant prostate cancer is only 32%. Combination treatment strategies to prevent disease recurrence are increasing, albeit in biomarker-unselected patients. Identifying a biomarker in CSPC to stratify patients who will progress on standard-of-care therapy could guide therapeutic strategies. EXPERIMENTAL DESIGN: Targeted deep sequencing was performed for the University of Illinois (UI) cohort (n = 30), and immunostaining was performed on a patient tissue microarray (n = 149). Bioinformatic analyses identified pathways associated with biomarker overexpression (OE) in the UI cohort, consolidated RNA sequencing samples accessed from Database of Genotypes and Phenotypes (n = 664), and GSE209954 (n = 68). Neutralizing antibody patritumab and ectopic HER3 OE were utilized for functional mechanistic experiments. RESULTS: We identified ERBB3 OE in diverse patient populations with CSPC, where it was associated with advanced disease at diagnosis. Bioinformatic analyses showed a positive correlation between ERBB3 expression and the androgen response pathway despite low dihydrotestosterone and stable expression of androgen receptor (AR) transcript in Black/African American men. At the protein level, HER3 expression was negatively correlated with intraprostatic androgen in Black/African American men. Mechanistically, HER3 promoted enzalutamide resistance in prostate cancer cell line models and HER3-targeted therapy resensitized therapy-resistant prostate cancer cell lines to enzalutamide. CONCLUSIONS: In diverse patient populations with CSPC, ERBB3 OE was associated with high AR signaling despite low intraprostatic androgen. Mechanistic studies demonstrated a direct link between HER3 and enzalutamide resistance. ERBB3 OE as a biomarker could thus stratify patients for intensification of therapy in castration-sensitive disease, including targeting HER3 directly to improve sensitivity to AR-targeted therapies.

Association of cardiovascular risk profile with premature all-cause and cardiovascular mortality in US adults: findings from a national study.

OBJECTIVE: To assess the association between cardiovascular risk factor (CRF) profile and premature all-cause and cardiovascular disease (CVD) mortality among US adults (age < 65). METHODS: This study used data from the National Health Interview Survey from 2006 to 2014, linked to the National Death Index for non-elderly adults aged < 65 years. A composite CRF score (range = 0-6) was calculated, based on the presence or absence of six established cardiovascular risk factors: hypertension, diabetes, hypercholesterolemia, smoking, obesity, and insufficient physical activity. CRF profile was defined as "Poor" (≥ 3 risk factors), "Average" (1-2), or "Optimal" (0 risk factors). Age-adjusted mortality rates (AAMR) were reported across CRF profile categories, separately for all-cause and CVD mortality. Cox proportional hazard models were used to evaluate the association between CRF profile and all-cause and CVD mortality. RESULTS: Among 195,901 non-elderly individuals (mean age: 40.4 ± 13.0, 50% females and 70% Non-Hispanic (NH) White adults), 24.8% had optimal, 58.9% average, and 16.2% poor CRF profiles, respectively. Participants with poor CRF profile were more likely to be NH Black, have lower educational attainment and lower income compared to those with optimal CRF profile. All-cause and CVD mortality rates were three to four fold higher in individuals with poor CRF profile, compared to their optimal profile counterparts. Adults with poor CRF profile experienced 3.5-fold (aHR: 3.48 [95% CI: 2.96, 4.10]) and 5-fold (aHR: 4.76 [3.44, 6.60]) higher risk of all-cause and CVD mortality, respectively, compared to those with optimal profile. These results were consistent across age, sex, and race/ethnicity subgroups. CONCLUSIONS: In this population-based study, non-elderly adults with poor CRF profile had a three to five-fold higher risk of all-cause and CVD mortality, compared to those with optimal CRF profile. Targeted prevention efforts to achieve optimal cardiovascular risk profile are imperative to reduce the persistent burden of premature all-cause and CVD mortality in the US.

Unfavorable social determinants of health and mortality risk by cardiovascular disease status: Findings from a National Study of United States Adults.

BACKGROUND: The association between cumulative burden of unfavorable social determinants of health (SDoH) and all-cause mortality has not been assessed by atherosclerotic cardiovascular disease (ASCVD) status on a population level in the United States. METHODS: We assessed the association between cumulative social disadvantage and all-cause mortality by ASCVD status in the National Health Interview Survey, linked to the National Death Index. RESULTS: In models adjusted for established clinical risk factors, individuals experiencing the highest level of social disadvantage (SDoH-Q4) had over 1.5 (aHR = 1.55; 95%CI = 1.22, 1.96) and 2-fold (aHR = 2.21; 95% CI = 1.91, 2.56) fold increased risk of mortality relative to those with the most favorable social profile (SDoH-Q1), respectively for adults with and without ASCVD; those experiencing co-occurring ASCVD and high social disadvantage had up to four-fold higher risk of mortality (aHR = 3.81; 95%CI = 3.36, 4.32). CONCLUSIONS: These findings emphasize the importance of a healthcare model that prioritizes efforts to identify and address key social and environmental barriers to health and wellbeing, particularly in individuals experiencing the double jeopardy of clinical and social risk.

Instant Assembly of Collagen for Scaffolding, Tissue Engineering, and Bioprinting.

Controllable assembly of cells and tissues offers potential for advancing disease and development modeling and regenerative medicine. The body's natural scaffolding material is the extracellular matrix, composed largely of collagen I. However, challenges in precisely controlling collagen assembly limit collagen's applicability as a primary bioink or glue for biofabrication. Here, we introduce a set of biopatterning methods, termed Tunable Rapid Assembly of Collagenous Elements (TRACE), that enables instant gelation and rapid patterning of collagen I solutions with wide range of concentrations. Our methods are based on accelerating the gelation of collagen solutions to instantaneous speeds via macromolecular crowding, allowing versatile patterning of both cell-free and cell-laden collagen-based bioinks. We demonstrate notable applications, including macroscopic organoid engineering, rapid free-form 3D bioprinting, contractile cardiac ventricle model, and patterning of high-resolution (below 5 (m) collagen filament. Our findings enable more controllable and versatile applications for multi-scale collagen-based biofabrication.

Volumetric Compression Shifts Rho GTPase Balance and Induces Mechanobiological Cell State Transition.

During development and disease progression, cells are subject to osmotic and mechanical stresses that modulate cell volume, which fundamentally influences cell homeostasis and has been linked to a variety of cellular functions. It is not well understood how the mechanobiological state of cells is programmed by the interplay of intracellular organization and complex extracellular mechanics when stimulated by cell volume modulation. Here, by controlling cell volume via osmotic pressure, we evaluate physical phenotypes (including cell shape, morphodynamics, traction force, and extracellular matrix (ECM) remodeling) and molecular signaling (YAP), and we uncover fundamental transitions in active biophysical states. We demonstrate that volumetric compression shifts the ratiometric balance of Rho GTPase activities, thereby altering mechanosensing and cytoskeletal organization in a reversible manner. Specifically, volumetric compression controls cell spreading, adhesion formation, and YAP nuclear translocation, while maintaining cell contractile activity. Furthermore, we show that on physiologically relevant fibrillar collagen I matrices, which are highly non-elastic, cells exhibit additional modes of cell volume-dependent mechanosensing that are not observable on elastic substrates. Notably, volumetric compression regulates the dynamics of cell-ECM interactions and irreversible ECM remodeling via Rac-directed protrusion dynamics, at both the single-cell level and the multicellular level. Our findings support that cell volume is a master biophysical regulator and reveal its roles in cell mechanical state transition, cell-ECM interactions, and biophysical tissue programming.

Adaptation to volumetric compression drives hepatoblastoma cells to an apoptosis-resistant and invasive phenotype.

Liver cancer involves tumor cells rapidly growing within a packed tissue environment. Patient tumor tissues reveal densely packed and deformed cells, especially at tumor boundaries, indicative of physical crowding and compression. It is not well understood how these physical signals modulate tumor evolution and therapeutic susceptibility. Here we investigate the impact of volumetric compression on liver cancer (HepG2) behavior. We find that conditioning cells under a highly compressed state leads to major transcriptional reprogramming, notably the loss of hepatic markers, the epithelial-to-mesenchymal transition (EMT)-like changes, and altered calcium signaling-related gene expression, over the course of several days. Biophysically, compressed cells exhibit increased Rac1-mediated cell spreading and cell-extracellular matrix interactions, cytoskeletal reorganization, increased YAP and ß-catenin nuclear translocation, and dysfunction in cytoplasmic and mitochondrial calcium signaling. Furthermore, compressed cells are resistant to chemotherapeutics and desensitized to apoptosis signaling. Apoptosis sensitivity can be rescued by stimulated calcium signaling. Our study demonstrates that volumetric compression is a key microenvironmental factor that drives tumor evolution in multiple pathological directions and highlights potential countermeasures to re-sensitize therapy-resistant cells. Significance statement: Compression can arise as cancer cells grow and navigate within the dense solid tumor microenvironment. It is unclear how compression mediates critical programs that drive tumor progression and therapeutic complications. Here, we take an integrative approach in investigating the impact of compression on liver cancer. We identify and characterize compressed subdomains within patient tumor tissues. Furthermore, using in vitro systems, we induce volumetric compression (primarily via osmotic pressure but also via mechanical force) on liver cancer cells and demonstrate significant molecular and biophysical changes in cell states, including in function, cytoskeletal signaling, proliferation, invasion, and chemoresistance. Importantly, our results show that compressed cells have impaired calcium signaling and acquire resistance to apoptosis, which can be countered via calcium mobilization.

Cardiovascular disease in Filipino American men and women: A 2023 update.

With more than 4.2 million people, Filipino Americans are the third largest Asian group in the US and the largest Southeast Asian group in the country. Despite relatively favorable average socioeconomic indicators compared to the general US population, Filipino Americans face a significant burden of traditional cardiovascular risk factors, particularly among men. Moreover, Filipino Americans have high rates of cardiovascular death, often occurring at a younger age compared to other minority groups and Non-Hispanic White adults. In view of these trends, in 2010 the American Heart Association designated Filipino Americans as a high cardiovascular risk group. Despite this, in 2023, Filipino Americans remain underrepresented in landmark cardiovascular cohort studies and are often over looked as a group at increased cardiovascular risk. In this updated narrative review, we summarize the current state of knowledge about the burden of cardiovascular risk factors and diseases experienced by the Filipino American population. Our aim is to inform enhanced clinical, population, and policy-level prevention interventions and boost research in this space.

Pharmacist-led review of empagliflozin and ertugliflozin following formulary update.

OBJECTIVES: To evaluate the appropriateness of the medication management for anyone who might have been affected by the Horizon New Jersey Health Medicaid Health Maintenance Organization (HNJH Medicaid HMO) formulary update from empagliflozin to ertugliflozin and to then optimize drug selection and monitoring. STUDY DESIGN: This is a single-center, 2-phase, pilot project led by 2 pharmacy students and the lead clinical pharmacist at a federally qualified health center in Trenton, New Jersey. METHODS: The primary outcome of the study is the number and percentage of patients whose prescription was changed inappropriately from empagliflozin to ertugliflozin. Secondary outcomes include the number and percentage of patients whose prescription was changed inappropriately because of failure to consider cardiovascular history and/or missed renal function checks and whether pharmacists were able to optimize therapy. Data were generated from electronic health record reports and analyzed in Microsoft Excel. RESULTS: A total of 126 unique patients were identified as receiving empagliflozin and/or ertugliflozin and 16 patients were switched from empagliflozin to ertugliflozin, all of whom had HNJH Medicaid HMO. Thirteen of the 16 (81.3%) patients were managed inappropriately based on their history of cardiovascular disease or inappropriate renal monitoring. Pharmacists recommended 22 interventions for patients who received empagliflozin and/or ertugliflozin, and all recommendations were accepted by providers. CONCLUSIONS: Following the HNJH Medicaid HMO's coverage update from empagliflozin to ertugliflozin, some patients received inappropriate therapy and providers accepted clinical pharmacists' recommendations to optimize therapy.

Race and Ethnicity Reporting and Enrollment Disparities in Clinical Trials Leading to FDA Approvals for Breast Cancer Between 2010 and 2020.

BACKGROUND: We determined the race and ethnicity demographics and reporting trends of clinical trials leading to Food and Drug Administration (FDA) approvals for breast cancer. METHODS: We collected enrollment and reporting data from clinical trials leading to FDA novel and new use approvals for breast cancer from 2010 to 2020 from Drugs@FDA, ClinicalTrials.gov, and associated journal manuscripts. Enrollment demographics were compared to the US cancer population estimates obtained using National Cancer Institute-Surveillance, Epidemiology, and End Results and 2010 US Census databases. RESULTS: Seventeen drugs received approval based on 18 clinical trials with a total enrollment of 12,334. For approvals from 2010 to 2015 and from 2016 to 2020, there was no significant difference in race (80% vs. 91.6%, P = .34) or ethnicity reporting (20% vs. 33.3%, P = .5) on ClinicalTrials.Gov, manuscripts, and FDA labels. For trials that reported race and ethnicity, White, Asian, Black, and Hispanic patients represented 73.8%, 16.4%, 3.7%, and 10.4% of trial participants. Relative to their US cancer incidence, Black (31% of expected) patients were underrepresented compared with White (90% of expected), Hispanic (115%), and Asian (327% of expected) patients. CONCLUSION: We observed no significant difference in race and ethnicity reporting in pivotal clinical trials leading to FDA approval for breast cancer from 2010 to 2020. Black patients were underrepresented in these pivotal trials relative to White, Hispanic, and Asian patients. Ethnicity reporting remained low throughout the study period. Innovative approaches are needed to ensure equitable benefit of novel therapeutics.

Defining Vascular Deserts to Describe Access to Care and Identify Sites for Targeted Limb Preservation Outreach.

BACKGROUND: Access to care plays a critical role in limb salvage in chronic limb-threatening ischemia (CLTI). A "medical desert" describes a community lacking access to medical necessities, resulting in increased morbidity and mortality. We sought to describe vascular deserts, which we defined as regions with decreased access to specialty care. METHODS: All California providers performing vascular surgery procedures were identified through online provider and health care facility searches. Facility participation in the Society for Vascular Surgery (SVS) Vascular Quality Initiative (VQI) lower extremity bypass (LEB) and peripheral vascular intervention (PVI) modules was also determined. Addresses were geocoded with a 30-mile surrounding buffer using ArcGIS (Geographic information systems), creating maps based on care type, including all providers performing vascular procedures, board-certified vascular surgeons, and facilities participating in VQI modules. Public census data overlayed on the maps demonstrated population composition in desert versus nondesert regions. Subsequently, data from the Healthy Places Index (HPI) was overlayed, providing data regarding 25 social factors, comprising an overall HPI score and percent, with lower scores corresponding to poorer health and outcomes. RESULTS: Maps depicting care regions demonstrated decreased provider coverage with increasing specialty care, with the VQI provider map showing the most prominent "desert" regions. When comparing nondesert versus desert regions by care type, demographics including race, the percentage of the population 200% below the poverty line, and the rate of uninsured residents were described. Social determinants of health were then described for desert and nondesert regions by care type, including the HPI percentage and specific domain factors. The percentage of uninsured residents was significant only in the desert and nondesert areas served by board-certified vascular surgeons (19.6 vs. 16.8%, P < 0.001). The mean HPI percentile was significantly lower in board-certified provider and VQI facility deserts than nondeserts (50.48% vs. 40.65%, P < 0.001 and 52.68% vs. 43.12%, P < 0.001, respectively). The economic and education factor percentiles were significantly lower in all desert populations, while the housing, social, and pollution factors were significantly higher in nondesert regions. Health care access, transportation, and neighborhood factor percentiles were significantly lower in board-certified and VQI facility deserts than in the nondesert areas. CONCLUSIONS: Access to vascular care plays a significant role in limb salvage. Through mapping vascular deserts, patient demographics, and social factors in desert regions are better understood, and areas that would benefit most from targeted outreach and limb preservation programs for CLTI are identified.

The role of molecular testing in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is highly aggressive and has few treatment options. To personalize therapy, it is critical to delineate molecular subtypes and understand inter- and intra-tumoral heterogeneity. Germline testing for hereditary genetic abnormalities is recommended for all patients with PDA and somatic molecular testing is recommended for all patients with locally advanced or metastatic disease. KRAS mutations are present in 90% of PDA, while 10% are KRAS wild type and are potentially targetable with epidermal growth factor receptor blockade. KRASG12C inhibitors have shown activity in G12C-mutated cancers, and novel G12D and pan-RAS inhibitors are in clinical trials. DNA damage repair abnormalities, germline or somatic, occur in 5-10% of patients and are likely to benefit from DNA damaging agents and maintenance therapy with poly-ADP ribose polymerase inhibitors. Fewer than 1% of PDA harbor microsatellite instability high status and are susceptible to immune checkpoint blockade. Albeit very rare, occurring in <1% of patients with KRAS wild-type PDAs, BRAF V600E mutations, RET and NTRK fusions are targetable with cancer agnostic Food and Drug Administration-approved therapies. Genetic, epigenetic, and tumor microenvironment targets continue to be identified at an unprecedented pace, enabling PDA patients to be matched to targeted and immune therapeutics, including antibody-drug conjugates, and genetically engineered chimeric antigen receptor or T-cell receptor - T-cell therapies. In this review, we highlight clinically relevant molecular alterations and focus on targeted strategies that can improve patient outcomes through precision medicine.

Microfluidic 'brain-on chip' systems to supplement neurological practice: development, applications and considerations.

Among the greatest general challenges in bioengineering is to mimic human physiology. Advanced efforts in tissue engineering have led to sophisticated 'brain-on-chip' (BoC) microfluidic devices that can mimic structural and functional aspects of brain tissue. BoC may be used to understand the biochemical pathways of neurolgical pathologies and assess promising therapeutic agents for facilitating regenerative medicine. We evaluated the potential of microfluidic BoC devices in various neurological pathologies, such as Alzheimer's, glioblastoma, traumatic brain injury, stroke and epilepsy. We also discuss the principles, limitations and future considerations of BoC technology. Results suggest that BoC models can help understand complex neurological pathologies and augment drug testing efforts for regenerative applications. However, implementing organ-on-chip technology to clinical practice has some practical limitations that warrant greater attention to improve large-scale applicability. Nevertheless, they remain to be versatile and powerful tools that can broaden our understanding of pathophysiological and therapeutic uncertainties to neurological diseases.

In this paper, the authors describe the role of microfluidic 'brain-on-chip' systems as a tool to model and study the human brain. While animal studies have provided significant insights, they lack the complexity of human brain tissue in order to verify the effects of drugs on patients, study complex physiological pathways or personalize regenerative therapies. This makes studying diseases of complex human organs challenging. Microfluidics is a field of study that can address these challenges by developing sophisticated and miniaturized devices that can chamber human tissue. These devices could allow scientists to better study diseases on a model that is accurate and controllable, allowing researchers to better understand complex diseases, assess drug efficacy to specific areas of the brain and potentially accelerate the development of new therapies. Herein, we characterize the principles, development and challenges of microfluidics and the role they have served in different neurological diseases.