Treatment Strategies Research Articles

Expert consensus on integrated medicine for tumor-related gastric injury and protection in China (2024 edition)

Neoplasm is one of the major causes of harm to human health. With the development of integrated medicine, more experts have begun to pay attention to tumor-related damage, among which gastric injury is common and seriously affects the quality of life of patients. The stomach is richly supplied with blood and nerves. Tumor treatment methods such as medication, surgery, and interventional therapy can impair its barrier function. Additionally, the tumor itself can harm the stomach through various mechanisms, primarily manifesting as symptoms like gastritis, erosion, ulceration, bleeding, and perforation. These conditions significantly affect the patient's quality of life and pose a serious threat to life.At present, the mechanisms of gastrointestinal tumors and other systemic tumors causing gastric injury are unclear, and there is a lack of relevant clinical and basic research. The diagnostic criteria and protective measures need to be supplemented and improved. To enhance the understanding of tumor-related gastric injuries and their management among professionals in related fields and to guide clinical practice, this expert consensus has been refined and formulated under the integrated medical concepts and based on the previous guidelines of the Chinese Anti-Cancer Association (CACA). It summarizes various tumor-related gastric injuries and protective treatment strategies, aiming to provide clinicians in oncology with a reference to address and prevent gastric injuries during the treatment of systemic diseases, thereby laying a foundation for further in-depth research in the future.

Call attention to the comprehensive diagnosis and treatment strategies of infertility caused by chronic endometritis

Chronic endometritis (CE) is a persistent inflammation of the endometrium caused by microbial infection, which is characterized by the infiltration of plasma cells into the endometrial stromal area. CE emerges as a critical determinant in the etiology of female infertility and is closely associated with adverse pregnancy outcomes, such as recurrent spontaneous abortion and repeated implantation failure, imposing a heavy burden on patients and their families. However, current understanding of CE-induced infertility remains superficial, leading to delays and inconsistent approaches in the diagnosis and treatment of the condition. Emphasizing the diagnosis and treatment of CE can help improve women's reproductive health, alleviate the economic and psychological pressures of patients and their families, resolve family conflicts and promote family and social harmony. This article provides an in-depth analysis of the diagnostic criteria and current application status of CE, its impact on endometrial receptivity and fallopian tubal function, as well as its interplay with other gynecological disorders. In alignment with clinical practice, we propose suggestions including enhancing the understanding of CE, strengthening publicity and education, standardizing the diagnostic process for CE, exploring the molecular mechanisms of CE and optimizing treatment strategies, in order to improve the comprehensive diagnosis and treatment strategies of CE-induced infertility and make greater contributions to the reproductive health of women in China.

Lumpy skin disease: a systematic review of mode of transmission, risk of emergence, and risk entry pathways.

Lumpy skin disease (LSD), a viral disease of cattle, can be acute, subacute, or inactive. It is distinguished by fever and the abrupt emergence of firm, confined cutaneous nodules that usually necrotize. Similar lesions may occur in the skeletal muscles and the mucosae of the digestive and respiratory tracts. It is an enzootic, rapidly explorative, and sometimes fatal infection, characterized by multiple raised nodules on the skin of infected animals. LSDV has a large genome, it is employed as a vaccine carrier, generating a new complex with other viral genes by homologous recombination. This review summarizes our current knowledge of lumpy skin disease (LSD), its impact on animal health, host-pathogen interaction, etiology, signs or symptoms, prevention, and treatment strategies.

Targeting MuRF1 to Combat Skeletal Muscle Wasting in Cardiac Cachexia: Mechanisms and Therapeutic Prospects.

Cardiac cachexia, the terminal stage of chronic heart failure, is characterized by severe systemic metabolic imbalances and significant weight loss, primarily resulting from skeletal muscle mass depletion. Despite the detrimental consequences, there is no standardized and clinically-approved intervention currently available for cardiac cachexia. In the context of cardiac cachexia, accelerated protein turnover, that is, inhibited protein synthesis and enhanced protein degradation, plays a crucial role in skeletal muscle wasting. This process is primarily mediated by various proteins encoded by atrogenes. Among them, the atrogene Trim63 (tripartite motif family 63) and its encoded protein MuRF1 have been extensively studied. This review article aims to elucidate the pathogenic mechanisms underlying skeletal muscle wasting in cardiac cachexia, describe the biochemical characteristics of MuRF1, and provide an overview of the investigation into MuRF1-targeting inhibitors. The ultimate goal is to offer novel strategies for the clinical treatment for skeletal muscle wasting associated with cardiac cachexia.

Multilayer Nanocarrier for the Codelivery of Interferons: A Promising Strategy for Biocompatible and Long-Acting Antiviral Treatment

Background: Interferons (IFNs) are cytokines involved in the immune response with a synergistic regulatory effect on the immune response. They are therapeutics for various viral and proliferative conditions, with proven safety and efficacy. Their clinical application is challenging due to the molecules’ size, degradation, and pharmacokinetics. We are working on new drug delivery systems that provide adequate therapeutic concentrations for these cytokines and prolong their half-life in the circulation, such as nanoformulations. Methods: Through nanoencapsulation using electrospray technology and biocompatible and biodegradable polymers, we are developing a controlled release system based on nanoparticles for viral infections of the respiratory tract. Results: We developed a controlled release system for viral respiratory tract infections. A prototype nanoparticle with a core was created, which hydrolyzed the polyvinylpyrrolidone (PVP) shell , releasing the active ingredients interferon-alpha (IFN-α) and interferon-gamma (IFN-γ). The chitosan (QS) core degraded slowly, with a controlled release of IFN-α. The primary and rapid effect of the interferon combination ensured an antiviral and immunoregulatory response from day one, induced by IFN-α and enhanced by IFN-γ. The multilayer design demonstrated an optimal toxicity profile. Conclusions: This formulation is an inhaled dry powder intended for the non-invasive intranasal route. The product does not require a cold chain and has the potential for self-administration in the face of emerging viral infections. This novel drug has applications in multiple infectious, oncological, and autoimmune conditions, and further development is proposed for its therapeutic potential. This prototype would ensure greater bioavailability, controlled release, fewer adverse effects, and robust biological action through the simultaneous action of both molecules.

Treatment indicators and prognostic factors in colorectal neuroendocrine neoplasms and adenocarcinoma with neuroendocrine differentiation: a single center retrospective study.

This study compared survival and metastasis occurrence between colorectal neuroendocrine neoplasms (cNEN) and colorectal adenocarcinoma with neuroendocrine differentiation (cNED) and further explored their prognostic factors and treatment indicators. Patients diagnosed as cNEN and cNED in West China Hospital from January 2009 to December 2020 were enrolled. The diagnosis and metastasis rates were calculated. Univariate and multivariate Cox analyses were conducted for progression-free survival (PFS) in cNEN surgical patients, and generalized linear regression was used for metastatic disease. The study enrolled 435 patients, including 257 neuroendocrine tumors (NET), 52 neuroendocrine carcinomas (NEC), 29 mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN), and 97 NED patients, of whom 202 received local resection, and 233 received radical resection. Metastasis rates were higher in MiNEN and NEC groups compared to other groups (NED: 28.9%, MiNEN: 58.6%, NEC: 65.4%, NET: 8.6%, p < 0.001). The liver is the main metastatic site in cNEN, whereas cNED metastasized to various sites. For NEC and MiNEN patients, colon location (p = 0.002) and T stage > 2 (p = 0.040) were associated with disease progression separately. Independent risk factors for metastatic NET included tumor grade G2/G3 (p < 0.001), colon location (p = 0.001), size ≥ 1cm (p = 0.005), and CK20 partial positive (p < 0.001). cNEN show high metastatic capacity and are challenging to diagnose. More aggressive treatment and follow-up strategies are necessary for those patients. NET tumor grade higher than G2, size larger than 1cm, or located in the colon should be managed with radical surgery.

Role of RNA G-Quadruplexes in the Japanese Encephalitis Virus Genome and Their Recognition as Prospective Antiviral Targets.

G-quadruplexes (GQs) have been primarily studied in the context of cancer and neurodegenerative pathologies. However, recent research has shifted focus to their existence and functional roles in viral genomes, revealing GQ-regulated key pathways in various human pathogenic viruses. While GQ structures have been reported in the genomes of emerging and re-emerging viruses, RNA viruses have been understudied compared to DNA viruses, including notable examples such as human immunodeficiency virus-1, hepatitis C virus, Ebola virus, Nipah virus, Zika virus, and SARS-CoV-2. The flavivirus family, comprising the Japanese encephalitis virus (JEV), poses a significant global threat due to recurring outbreaks yet lacks approved antivirals. In this study, we identified and characterized eight putative G-quadruplex-forming motifs within essential genes involved in genome replication, assembly, and internalization in the host cell, conserved across different JEV isolates. The formation and stability of these motifs were validated through a multitude of biophysical and cell-based assays. The interaction and binding affinity of these motifs with the known GQ-binding ligand BRACO-19 were supported by biophysical assays, confirming the capability of these motifs to form GQ structures. Notably, BRACO-19 also exerted antiviral properties through reduction of viral replication and infectious virus titers as well as inhibition of viral protein expression, as evaluated by the cell-based assays. This comprehensive molecular characterization of G-quadruplex structures within the JEV genome highlights their potential as promising antiviral targets for intervention strategies against JEV infection through GQ-specific ligands.

Clinical impact of TP53 functional mutations in patients with metastatic colorectal cancer treated with bevacizumab and chemotherapy

Abstract Background Clinical and experimental studies indicate that the tumor protein p53 (TP53) gene loss of function due to missense mutations (MMs) may confer sensitivity to anti-angiogenics. This effect seems to be linked to cross-talk mechanisms among TP53, vascular endothelial growth factor (VEGF), and VEGF receptors. We investigated whether specific TP53 MMs are associated with clinical outcomes of patients with metastatic colorectal cancer (mCRC) treated with first-line chemotherapy plus Bevacizumab. The study focused on KRAS-mutated, liver-only mCRC cases as a homogeneous subgroup that may represent a relevant setting for exploring this association. Materials and methods MMs were identified on primary tumors. MMs were classified by mutant-specific residual transcriptional activity scores (TP53RTAS) as transcriptionally inactive (TP53inactive = TP53RTAS 0%) or active (TP53active = TP53RTAS ≥ 1%) and used for stratifying patients in progression-free survival (PFS), response rate, and overall survival (OS) analyses. Results The study population consisted of 62 patients. MMs were found in 39 cases (62%) with 16 having TP53inactive and 23 TP53active MMs. Patients with TP53inactive MMs showed better PFS in comparison with the remaining groups (wild-type and TP53active). This effect was retained in the multivariate model. A similar clinical impact was observed in the OS analysis. There was a significant difference in the overall response rate and rate of post-treatment resection of liver metastases between the TP53inactive and the wild-type or TP53active MMs cases. Conclusions Specific TP53 MMs may identify sub-groups of patients who benefit from Bevacizumab-based systemic therapy and these findings could lead to novel tailored treatment strategies in this setting.

Current issues in the treatment of adolescent idiopathic scoliosis: a comprehensive narrative review.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional deformity of unknown etiology that commonly affects adolescents, imposing significant socioeconomic burdens. Effective management necessitates a comprehensive approach that takes into account multiple factors, including growth potential and psychological issues. Despite significant advancements in AIS management, several questions regarding optimal treatment strategies persist. Recent technological advancements are transforming the treatment landscape, encompassing advancements in bracing, robotic-assisted deformity corrections, and other interventions. This review explores current issues debated in the literature concerning the treatment of AIS, focusing on contemporary high-level evidence (e.g., meta-analyses and randomized controlled trials). Furthermore, this review explores cutting-edge developments and future directions in AIS management, including the integration of artificial intelligence and augmented reality.

Advancements of anticancer agents by targeting the Hippo signalling pathway: biological activity, selectivity, docking analysis, and structure-activity relationship.

The Hippo signalling pathway is prominent andgoverns cell proliferation and stem cell activity, acting as a growth regulator and tumour suppressor. Defects in Hippo signalling and hyperactivation of its downstream effector's Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) play roles in cancer development, implying that pharmacological inhibition of YAP and TAZ activity could be an effective cancer treatment strategy. Conversely, YAP and TAZ can also have beneficial effects in promoting tissue repair and regeneration following damage, therefore their activation may be therapeutically effective in certain instances. Recently, a complex network of intracellular and extracellular signalling mechanisms that affect YAP and TAZ activity has been uncovered. The YAP/TAZ-TEAD interaction leads to tumour development and the protein structure of YAP/TAZ-TEAD includes three interfaces and one hydrophobic pocket. There are clinical and preclinical trial drugs available to inhibit the hippo signalling pathway, but these drugs have moderate to severe side effects, so researchers are in search of novel, potent, and selective hippo signalling pathway inhibitors. In this review, we have discussed the hippo pathway in detail, including its structure, activation, and role in cancer. We have also provided the various inhibitors under clinical and preclinical trials, and advancement of small molecules their detailed docking analysis, structure-activity relationship, and biological activity. We anticipate that the current study will be a helpful resource for researchers.

PI3K/AKT signaling and neuroprotection in ischemic stroke: molecular mechanisms and therapeutic perspectives.

It has been reported that the PI3K/AKT signaling pathway plays a key role In the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke, with a focus on the PI3K/AKT signaling pathway.The key findings include the following: (1) The complex pathological mechanisms of ischemic stroke can be categorized into five major types: excitatory amino acid toxicity, Ca2+ overload, inflammatory response, oxidative stress, and apoptosis. (2) The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke, which primarily involves the NF-kB, NRF2, BCL-2, mTOR, and endothelial NOS signaling pathways. (3) Natural products, including flavonoids, quinones, alkaloids, phenylpropanoids, phenols, terpenoids, and iridoids, show great potential as candidate substances for the development of innovative anti-stroke medications. (4) Recently, novel therapeutic techniques, such as electroacupuncture and mesenchymal stem cell therapy, have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway, providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke. Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

Guiding treatment decisions in renal cell carcinoma: the role of biomarkers and clinical factors.

Immune checkpoint inhibitors (ICIs) have transformed the treatment landscape for metastatic renal cell carcinoma (mRCC), significantly improving overall survival and achieving durable responses. This review is timely due to the increasing number of ICI-based regimens now considered standard care for RCC. There is an urgent need to identify reliable biomarkers that can predict therapeutic responses and resistance, a key challenge in current research. While tumor-specific factors such as pathological characteristics, genomic mutations, and transcriptional profiles have been extensively studied, no definitive predictive biomarker has yet emerged. Additionally, advanced technologies are being explored to address tumor heterogeneity. Recent research has focused on novel areas such as the microbiome, radiomics, and spatial transcriptomics, which show promise as potential biomarkers. The translation of these emerging biomarker findings into clinical practice is essential to improving personalized treatment strategies for RCC. Until reliable biomarkers are clinically available, clinical factors may play a pivotal role in guiding individualized treatment decisions to optimize patient outcomes.

Conversion surgery for esophageal and esophagogastric junction cancer.

As a result of the recent advances in first-line treatment including chemotherapy, radiation therapy, targeted therapy, and immune checkpoint inhibitor immunotherapy (ICI) for locally advanced/metastatic initially unresectable esophageal and esophagogastric junction cancer, surgery aiming at cure after initial treatment, so-called "conversion surgery" has become more common in this field. Several studies have indicated encouraging survival outcomes for patients after conversion surgery with R0 resection. However, various issues, such the utility and the safety of conversion surgery remain unclear. In this review, we will focus on the surgical treatment for initially unresectable esophageal and esophagogastric junction cancer after first- or later- line treatment and review recent evidence regarding the safety and the efficacy of conversion surgery. Multidisciplinary treatment including surgery may serve as a novel treatment strategy for esophageal and esophagogastric junction cancer, thus provide a curative treatment option and potentially contribute to better prognosis for initially untreatable diseases.

Advancements in the Treatment of Diuretic Resistance in Congestive Heart Failure.

This narrative evaluates the dynamic developments that have significantly transformed treatment strategies in the constantly evolving domain of diuretic resistance (DR) management in congestive heart failure (CHF). The discourse explores historical challenges and the current state of therapeutic approaches as it investigates the crucial matter of DR in patients with CHF. An introduction provides a synopsis of the pivotal function diuretics performed in the management of fluid excess and the intricacies associated with CHF. The narrative explores the progressive exposure of the constraints that traditional treatments face, thus underscoring the persistent issue of DR and the imperative for innovative methodologies. The text underscores advancements in pharmacotherapy that demonstrate efficacy in surmounting resistance, including innovative diuretics and combination therapies. Furthermore, it outlines the pivotal shift towards personalized medicine, an approach that transforms the results of treatments through the integration of genetic knowledge and individualized strategies. Furthermore, the text delves into nonpharmacological strategies, including ultrafiltration and renal denervation, that enhance the overall comprehension of the intricate battle against diuretic resistance. In summary, this narrative exemplifies resolute perseverance in the pursuit of solutions, presenting a promising future wherein various developments converge to restore hope in regard to the control of DR and the improvement of the health status of chronic heart failure patients.

Integrated immunogenomic analyses of single-cell and bulk profiling construct a T cell-related signature for predicting prognosis and treatment response in osteosarcoma.

T cells play a crucial role as regulators of anti-tumor activity within the tumor microenvironment (TME) and are closely associated with the progression of osteosarcoma (OS). Nevertheless, the specific role of T cell-related genes (TCRGs) in the pathogenesis of OS remains unclear. First, we processed single-cell RNA sequencing (scRNA-seq) data of OS from the public databases and performed cell annotation. We identified highly variable genes in each cell type using the "FindAllMarkers" function, explored the distribution of different clusters, and investigated inter-cellular communication patterns via the "CellChat" framework. Then, we used multivariate Cox analysis to construct a TCRG and developed a nomogram to predict survival probabilities for OS patients. Finally, we validated the aforementioned results using various cell lines and investigated the immune cell infiltration, expression of immune checkpoints, chemotherapy sensitivity, and the efficacy of targeted therapies across different risk groups. From the scRNA-seq data, we identified 3,000 highly variable genes, presented the top 10 genes, and validated the expression of core genes across different cell lines.Moreover, our analysis delved into interactions between T cells and other cell types. Our analyses constructed a predictive T cell-related signature (TCRS) that incorporated these prognostic TCRGs, showing a clear prognostic separation between the high-risk and low-risk OS patient groups in multiple cohorts. Survival analysis indicated better outcomes for patients classified in the high-risk group. The low-risk group exhibited elevated levels of CD4 memory resting T cells, contrasting with the higher levels of macrophage M0 observed in the high-risk group via the CIBERSORT algorithm. Furthermore, we observed that the low-risk group exhibitedAQ1 significant up-regulation of immune checkpoint genes (ICGs) and lower Tumour Immune Dysfunction and Exclusion (TIDE) scores, suggesting that they may be suitable for immunotherapy. Conversely, the high-risk group appeared more responsive to chemotherapy and targeted therapies, according to our drug sensitivity analysis. In conclusion, our study identified TCRGs, constructed and validated a TCRS for OS, and assessed immune response and drug sensitivity in different risk groups of OS patients. These findings provide novel insights into personalized treatment strategies for OS, potentially guiding more effective therapeutic interventions.

Overview of the ASCO 2024 data on head and neck surgery

At the 2024 international cancer congress of the American Society of Clinical Oncology (ASCO), studies on immuno-oncological therapeutic approaches for head and neck cancers once again took center stage. Following the trend of recent years, neoadjuvant immunotherapy has now reached acentral role, and purely surgical studies have become increasingly scarce. This review article summarizes abstracts presented at the 2024 ASCO Annual Meeting that focus on surgical therapy or in which surgery was asignificant component of the study protocol. As part of the combination therapies, study results on neoadjuvant treatment strategies are also presented. Additionally, promising new developments are discussed, including the treatment of laryngeal papillomatosis, new considerations on the necessary extent of neck dissection, follow-up care for human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC), and the prevention of platinum-induced inner ear hearing loss.

Swelling Induced Hardening and Degradation Induced Slow-Expansion Hydrogel for a Modified Cervical Spinal Cord Compression Animal Model.

This study presents the development of a polyurethane hydrogel (PUG) for use in a chronic cervical spinal cord compression animal model, leveraging microphase separation and dynamic covalent bonds to achieve swelling induced hardening and degradation-induced slow expansion. PUG-SS and PUG-SS-60% were synthesized with varying disulfide bond concentrations, offering controllable degradation rates and mechanical properties. The hydrogels demonstrated significant swelling-induced hardening and maintained compression above the cervical spinal cord's intrinsic modulus. MRI and histopathological analyses confirmed effective and sustained spinal cord compression, with PUG-SS-60% showing prolonged effects. Behavioral tests, including the BBB locomotor scale, von Frey pain test, and catwalk gait analysis, indicated quicker motor function recovery with PUG-SS and sustained compression with PUG-SS-60%. In vitro cytotoxicity assays showed no significant hydrogel-induced cell death. This study underscores the potential of PUG-SS-60% for providing controlled, sustained compression in chronic spinal cord compression models, paving the way for advanced nonsurgical treatment strategies and improved understanding of degenerative cervical myelopathy (DCM) pathology.

Adult-onset intramedullary teratomas: systematic review with outcome analysis.

Intramedullary mature teratomas in adults are rare tumors that pose significant diagnostic and therapeutic challenges due to their diverse tissue composition and intramedullary location. This review, which includes an illustrative case, aims to provide a comprehensive overview of the clinical presentation, diagnosis, treatment, and outcomes of adult intramedullary mature teratomas through a systematic review of 89 cases. A systematic review was conducted following PRISMA guidelines, using keyword combinations in PubMed, MEDLINE, and Web of Science databases until June 2024. Inclusion criteria were adult patients (> 18 years) with histopathologically confirmed intramedullary mature teratomas. Statistical analyses examined relationships between the extent of resection (EoR), tumor location, and patient outcomes. Among the 89 cases, the mean age was 39.94 ± 13.52 years, with a male-to-female ratio of 1.39:1. Tumors were most commonly located in the conus region (51.2%). Surgical resection was the primary treatment, with 43 cases undergoing partial resection and 33 gross total resection. No statistically significant differences in outcomes were found between EoR, sex, associated anomalies, or specific outcomes. However, younger patients showed improved outcomes for lower limb weakness and sphincter dysfunction. Recurrence was noted in three cases, all located in the conus. Intramedullary mature teratomas require a nuanced approach that balances complete resection and neurological preservation. Early diagnosis and individualized surgical planning are crucial for optimizing outcomes. Despite the challenges, effective management is achievable, and ongoing research is essential to refining treatment strategies for this rare tumor.

Machine learning predictive models to guide prevention and intervention allocation for anxiety and depressive disorders among college students

AbstractCollege student mental health has been a critical concern for professional counselors. Anxiety and depressive disorders have become increasingly prevalent over the past decade. Utilizing machine learning, a subset of artificial intelligence (AI), we developed predictive models (i.e., eXtreme Gradient Boosting [XGBoost], Random Forest, Decision Tree, and Logistic Regression) to identify US college students at heightened risk of diagnosable anxiety and depressive disorders. The dataset included 61,619 students from 133 US higher education institutions and was partitioned into a 90:10 ratio for training and testing the models. We employed hyperparameter tuning and cross‐validation to optimize model performance and examined multiple measures of predictive performance (e.g., area under the receiver operating characteristic curve [AUC], accuracy, sensitivity). Results revealed strong discriminative power in our machine learning predictive models with AUC of 0.74 and 0.77, indicating current financial situation, sense of belonging on campus, disability status, and age as the top predictors of anxiety and depressive disorders. This study provides a practical tool for professional counselors to proactively identify students for anxiety and depressive disorders before these conditions escalate. Application of machine learning in counseling research provides data‐driven insights that help enhance the understanding of mental health determinants, guide prevention and intervention strategies, and promote the well‐being of diverse student populations through counseling.

Cardiovascular Precision Medicine and Remote Intervention Trial Rationale and Design

Background: It has recently been shown that excessive fluctuation in blood pressure readings for an individual over time is closely associated with poor outcomes, including increased risk of cardiovascular mortality, coronary heart disease and stroke. Fluctuations may be associated with inconsistent adherence to medical recommendations. This new marker of risk has not yet been incorporated into a monitoring and intervention strategy that seeks to reduce cardiovascular risk by identifying patients through an algorithm tied to their electronic health record (EHR). Methods: We describe the methods used in an innovative “proof of concept” trial using CP&amp;R (Cardiovascular Precision Medicine and Remote Intervention). A blood pressure variability index is calculated for clinic patients via an EHR review. Consenting patients with excessive variability are offered a remote intervention aimed at improving adherence to medical recommendations. The outcomes include the ability to identify and engage the identified patients and the effects of the intervention on blood pressure variability using a pre–post comparison design without parallel controls. Conclusions: Our innovative approach uses a recently identified marker based on reviewing and manipulating EHR data tied to a remote intervention. This design reduces patient burden and supports equitable and targeted resource allocation, utilizing an objective criterion for behavioral risk. This study is registered under ClinicalTrials.gov Identifier: NCT05814562.