Therapy Management Research Articles

Opportunities for digitally-enabled personalization and decision support for pediatric growth hormone therapy.

Smart technologies and connected health are providing opportunities for improved healthcare for chronic conditions. Acceptance by healthcare professionals (HCPs) and patients is crucial for successful implementation. Evidence-based standards, technological infrastructure and regulatory processes are needed to integrate digital tools into clinical practice. Personal health records provide continuity and aid decision-making, while machine-learning algorithms may help in optimizing therapies and improving outcomes. Digital healthcare can negate geographical barriers, enabling patients in remote areas to access specialist endocrine expertise. We review available and developing digital tools to manage care for patients requiring growth hormone (GH) therapy for growth failure conditions. GH is most often administered via daily injections over several years; continuous adherence is necessary but may become insufficient. Future development and integration of electronic platforms for GH therapy requires involvement of all stakeholders in design-thinking approaches and human-factor testing. Growzen Connect is an innovative digital ecosystem designed to increase the management and monitoring of GH therapy, comprising the easypod device and connected mobile apps. It provides a real-time overview of a patient's therapy, including adherence and growth response, which aids decision-making by HCPs and empowers patients to engage in their therapy journey. Incorporating prediction models for adherence and growth in the ecosystem helps patients build treatment habits and allows issues to be addressed in a timely fashion. A connected ecosystem for GH therapy can enhance outcomes and empower patients, fostering a collaborative and patient-centered approach that is more proactive, beyond the traditional clinic-based approach.

LITERATURE REVIEW: THE OMICS STUDY FOR DETERMINING BIOMARKERS IN HUMAN SERUM AND PLASMA WITH DIFFERENT COVID-19 SEVERITY

The severity of COVID-19 provides information on various stages of changes in the body's normal state in various parameters called biological markers (biomarkers) as the initial identification that facilitates management, selection, and total outcomes in therapy. These biomarkers were selected from the selection of samples that are often used in the advanced diagnosis of COVID-19, serum and plasma. This study aims to determine what biomarkers are measured in serum and plasma samples of COVID-19 patients. This literature review is classified as non-experimental, qualitative, and descriptive research. The inclusion criteria are the full-text journals published within the last two years regarding biomarkers in the serum and plasma of COVID-19 patients. Based on these criteria, 49 relevant articles were obtained. The results show that changes occur in the protein, lipid, and metabolite in serum and plasma by the omics approach. These alterations can be in the form of increasing or decreasing levels of each parameter determined through various analytical methods. The biomarkers profile correlates with the severity of COVID-19 as well as with host cells.

"Rocking" Continuous Renal Replacement Therapy Management in Children and Young Adults With Sepsis: Impact of Hemodynamic Support on Outcomes.

"Rocking" Continuous Renal Replacement Therapy Management in Children and Young Adults With Sepsis: Impact of Hemodynamic Support on Outcomes.

A Mem-dELISA platform for dual color and ultrasensitive digital detection of colocalized proteins on extracellular vesicles

Accurate, multiplex, and ultrasensitive measurement of different colocalized protein markers on individual tumor-derived extracellular vesicles (EVs) and dimerized proteins with multiple epitopes could provide insights into cancer heterogeneity, therapy management and early diagnostics that cannot be extracted from bulk methods. However, current digital protein assays lack certain features to enable robust colocalization, including multi-color detection capability, large dynamic range, and selectivity against background proteins. Here, we report a lithography-free, inexpensive (< $0.1) and ultrasensitive dual-color Membrane Digital ELISA (Mem-dELISA) platform by using track-etched polycarbonate (PCTE) membranes to overcome these shortcomings. Their through-pores remove air bubbles through wicking before they are sealed on one side by adhesion to form microwells. Immunomagnetic bead-analyte complexes and substrate solution are then loaded into the microwells from the opposite side, with >80% loading efficiency, before sealing with oil. This enables duplex digital protein colorimetric assay with beta galactosidase and alkaline phosphatase enzymes. The platform achieves 5 logs of dynamic range with a limit of detection of 10 aM for both Biotinylated β-galactosidase (B-βG) and Biotin Alkaline Phosphatase Conjugated (B-ALP) proteins. We demonstrate its potential by showing that a higher dosage of paclitaxel suppresses EpCAM-positive EVs but not GPC-1 positive EVs from breast cancer cells, a decline in chemo-resistance that cannot be detected with Western blot analysis of cell lysate. The Mem-dELISA is poised to empower researchers to conduct ultrasensitive, high throughput protein colocalization studies for disease diagnostics, treatment monitoring and biomarker discovery.

Management of antithrombotic therapy in patients undergoing dental procedures

A growing number of patients receiving antithrombotic therapy require dental procedures. Dental interventions in these patients can be challenging, as the risk of bleeding from the continuation of antithrombotic therapy needs to be weighed against the thromboembolic risk associated with drug interruption or de-escalation. Most minor dental procedures, including simple dental cleaning and filling, pose minimal bleeding risk, and antiplatelet or anticoagulation therapy can be continued without interruption. Local hemostatic measures, such as tranexamic mouthwash, can be used, as needed, to reduce bleeding events following these interventions. Managing antithrombotic therapy during more invasive dental interventions and oral surgeries with a higher risk of perioperative bleeding necessitates the consideration of specific factors influencing the bleeding risk and thromboembolism. In patients receiving antithrombotic therapy for primary prevention, temporary interruption is reasonable. In others, the decisions may be more complex and more nuanced. In this article, we review the current evidence for managing patients receiving oral antiplatelet or anticoagulant drugs scheduled for various dental procedures and present a practical approach for the periprocedural management of antithrombotic treatments.

Construction of knowledge sharing network indicator system for medication therapy management service training teams based on social network analysis

BackgroundBased on the perspective of social network theory, this study explored the network indicator system that facilitated optimal knowledge sharing effect in Medication Therapy Management Services (MTMS) training teams. The aim was to provide a reference for optimizing MTMS training and improving training quality.MethodsUtilizing social network analysis combined with a questionnaire survey, a knowledge sharing matrix for MTMS training teams was constructed. Knowledge sharing behavior was assessed from three perspectives: individual networks, whole networks, and cohesive subgroups.ResultsIndividual network analysis showed that the knowledge sharing effect within the training team reached its peak when the out-degree centrality was ≥ 3.5, in-degree centrality was ≥ 2.5, eigenvector centrality was ≥ 0.065, and closeness centrality was ≥ 7.86. Whole network analysis indicated that the optimal knowledge sharing effect occurred when the network density of the training team was higher than 0.0343 and the training size was less than 117 participants. Cohesion subgroups analysis demonstrated that knowledge sharing was more effective when members with similar working years participated in training together.ConclusionsThe knowledge sharing indicator system developed for MTMS training teams, based on social network analysis, can assist in optimizing the MTMS training model and improving training effectiveness.

Duration, Cost, and Escalation of Care Events for Physical Therapy Management of Low Back Pain in Service Members With Limb Loss.

Physical therapy (PT) is recommended as a primary treatment for low back pain (LBP), a common and impactful musculoskeletal condition after limb loss. The purpose of this brief report is to report the duration and cost of PT care, and subsequent escalation of care events, for LBP in service members with and without limb loss. This was a retrospective cohort, descriptive study. Service members with and without limb loss (matched) who received PT for LBP at a military treatment facility from 2015 to 2017 were included. Duration of PT care, number of PT visits, and escalation of care events 1 year after PT were extracted from medical records. Escalation of care events was identified as epidural steroid injections, referrals to specialists (e.g., orthopedists, spine surgeons, and pain management), and LBP-related hospitalizations.LBP-related PT encounters were queried; duration of care, number of visits, and cost of care were quantified. Escalation of care events, including opioid prescription, epidural steroid injections, specialty referrals, and hospitalizations, were identified up to 1 year after PT care. The average course of PT care for LBP was 12.9 more visits, 48.7 days longer, and $764.50 more expensive in service members with limb loss (n = 16) vs. those without limb loss (n = 48). Higher rates of opioid prescriptions and specialty referrals were observed in service members with limb loss. This study suggests that service members with limb loss and LBP received higher quantities and longer durations of PT than those without limb loss, yielding a nearly 4 times higher cost of PT.

Emerging Thrombotic Disorders Associated with Virus-Based Innovative Therapies: From VITT to AAV Gene Therapy-Related Thrombotic Microangiopathy.

Gene therapy is a promising therapeutic approach for treating life-threatening disorders. Despite the clinical improvements observed with gene therapy, immune responses either innate or adaptive against the vector used for gene delivery, can affect treatment efficacy and lead to adverse reactions. Thrombotic microangiopathy (TMA) is a thrombosis with thrombocytopenia syndrome (TTS) characterized by microangiopathic hemolytic anemia, thrombocytopenia, and small vessel occlusion known to be elicited by several drugs, that has been recently reported as an adverse event of adeno-associated virus (AAV)-based gene therapy. TMA encompasses a heterogenous group of disorders, its classification and underlining mechanisms are still uncertain, and still lacks validated biomarkers. The identification of predictors of TMA, such as vector dose and patient characteristics, is a pressing need to recognize patients at risk before and after AAV-based gene therapy administration. This review aims to explore the literature on TMA associated with AAV-based gene therapy in the larger context of TMA (i.e., hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, and other drug-related TMAs). Considering the wide attention recently gained by another TTS associated with a non-gene therapy viral platform (adenovirus, AV COVID-19 vaccine), namely vaccine-induced immune thrombocytopenia and thrombosis (VITT), AAV gene therapy-related TMA mechanisms will be discussed and differentiated from those of VITT to avoid recency bias and favor a correct positioning of these two recently emerged syndromes within the heterogenous group of drug-related TTS. Finally, the review will discuss strategies for enhancing the safety and optimize the management of AAV-based gene therapy that is emerging as an efficacious therapeutic option for disparate, severe, and often orphan conditions.

Understanding Treatment Decisions and Management for Patients with Advanced Renal Cell Carcinoma Using Hypothetical Case Studies: A Vodcast.

In recent years, the armamentarium of therapies for the management of advanced renal cell carcinoma (aRCC) has grown. Combination therapies, including immuno-oncology (IO) agents and tyrosine kinase inhibitors [TKIs (IO-TKI)], and IO-IO combinations, are now approved for first-line treatment of aRCC. Decisions regarding the use of these combinations, IO-IO versus IO-TKI, can be challenging, as they have not been compared in a randomized trial; each of these combinations have been compared with sunitinib alone. In addition, patient-, disease-, and treatment-based factors must be evaluated in the decision-making process. More important is the consideration of patient management during treatment and optimal detection and management of toxicities to ensure continued benefit. In this vodcast, two experts in the field of kidney cancer will present case studies that represent typical patients seen in practice. The faculty will discuss treatment approaches, adverse event management, and which factors to consider during the treatment decision-making process. Viewers of the vodcast will get a better understanding of clinical trial outcomes related to an IO-TKI combination, such as axitinib plus pembrolizumab, that they can apply to their practice immediately. In addition, they will gain real-world insight into how experts approach the treatment of patients with aRCC and, more importantly, therapy management.

Incidence and clinical impact of inappropriate periprocedural and perioperative management of antiplatelet therapy

Background and aimsThere is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in “real life” in Spain. MethodsA prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy. ResultsWe included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents. ConclusionsDespite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the “real world” remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic.

Protocolo terapéutico y seguimiento del paciente con diabetes mellitus tipo 1 y obesidad

Treatment protocol and follow-up of patients with type 1 diabetes and obesity This protocol focuses on the management of obesity in patients with type 1 diabetes mellitus (DM1), a growing problem due to factors such as lifestyle, insulin treatment, and hypoglycemia. The approach includes four key pillars: nutrition therapy, drug therapy, physical activity, and management of insulin therapy. Nutrition therapy is the first line of treatment and is based on calorie reduction and a diet rich in fiber. In addition, there are pharmacological options for the management of overweight in patients with DM1, although they have specific challenges, such as euglycemic diabetic ketoacidosis. Physical activity and the adjustment of insulin therapy also play an essential role in weight and glycemic control. In severe cases, bariatric surgery is a viable option for patients with severe obesity.

International Burn Disaster Nursing: Care, Commitment, Compassion, and Cost.

Burn mass casualty incidents can overwhelm local resources, challenging effective communication, triage, and provision of care. International responders can help by providing education and direct patient care. On November 5, 2021, a fuel tanker truck exploded in Freetown, Sierra Leone, killing or injuring hundreds of people. The needs of the severely burned survivors overwhelmed local resources, requiring an international response. Burn specialist teams from several countries, including the United States, were deployed to provide assistance. Members of the US burn care team educated local health care practitioners about wound care, physical therapy, and fluid and pain management. Educational content was delivered through lecture and discussion, case studies, clinical application, and bedside teaching. Demonstration of cultural competence and humility, as well as attentiveness to nuances of local communication, helped avoid ethnocentrism and other barriers to collaboration. Public congratulations and formal completion certificates were used to provide meaningful recognition of successful class participation. Before the lecture and discussion intervention, 57 students participating in a pretest assessment had an average score of 53.9% (high, 80%; low, 27.5%). After the intervention, 38 students participating in a posttest assessment had an average score of 79.3% (high, 95%; low, 55%), and local health care providers delivered care with more attention to patient comfort and shared new knowledge with colleagues. Providing optimal burn care and education under austere conditions requires cultural humility and a spirit of inquiry. Attentiveness to communication and cultural nuances promotes collaboration, improves educational effectiveness, and builds local burn care capacity.

Distinction of papillary and adamantinomatous craniopharyngioma: Clinical features, surgical nuances and hypothalamic outcomes

ObjectiveUnderstanding the differences of suprasellar papillary and adamantinomatous craniopharyngiomas (PCPs/ACPs) is pivotal for target therapy, surgical strategy or postoperative management. Here, the clinical features, surgical nuances and postoperative hypothalamic outcomes of PCPs were systematically recapitulated. Methods24 PCPs and 52 ACPs underwent initial surgery were retrospectively reviewed. Clinical data, quantified third ventricle (3rd V) occupation and optic chiasm distortion were compared, as well as intra-operative findings, operating notes and prognosis. Moreover, analysis of tumor/3rd V relationship and hypothalamic outcomes were also performed. ResultsTumors were more likely to occupies the 3rd V cavity in PCPs. Chiasm distortion of “compressed forward” was the most common pattern (45.8 %) in PCPs, whereas “stretched forward” pattern accounted the highest (42.5 %) in ACPs. Besides, round-shaped with less calcification, duct-like recess, solid consistency, rare subdiaphragmatic invasion, visible lower stalk and improved postoperative visual outcome were more frequently observed in PCPs. The basal membranes of the tumor epithelium and the reactive gliosis were separated by a layer of collagen fibers in most PCPs, which differs from ACPs in the morphological examination of tumor/3rd V floor interface. In daytime sleepiness and memory difficulty, the PCPs showed significantly better outcomes than the ACPs groups, and PCPs suffered less postoperative weight gain (p < 0.05) than ACPs among adult-onset cases. ConclusionPCPs are different from ACPs regards the clinical features, operative techniques and outcomes. If necessary, PCPs are suggested more amenable to total removal since its less invasiveness to the 3rd V floor and better hypothalamic outcomes.

Detection and Interpretation of Clonal Hematopoiesis Variants during Routine Solid Tumor Next-Generation Sequencing: A Single-Institution Experience

Clonal hematopoiesis (CH) and Clonal Cytopenia of Undetermined Significance (CCUS) are recently recognized diagnostic entities that serve as an independent risk factor for cardiovascular disease and myeloid malignancy. CH is an incidental finding and evaluation of the incidence of CH/CCUS associated mutations in solid tumor Next Generation Sequencing (NGS) samples was undertaken to better understand the prevalence of mutations in this population. A retrospective review of clinical sequencing data for solid tumor malignancies diagnosed February 2022-April 2023 on NGS data was performed. Cases were reviewed for variants in genes associated with CH/CCUS. Variant allele frequencies and other factors of the sequencing data were assessed for determining risk of CH/CCUS. 2,479 cases were evaluated during the study period. Of these, 29 cases demonstrated potential CH/CCUS associated mutations with a total of 33 variants identified. These were identified in a variety of tumor types, with gliomas being the most common. Significant cardiac histories were found in over half of cases identified and few cases had abnormal blood counts. Detailed criteria for flagging variants as suspicious for CH and recommend these criteria as future guidelines for reporting are described. These variants are incidental findings which require more extensive follow up or change in therapy management utilizing a single institutional cohort.

Physical Therapy Management of Congenital Muscular Torticollis: A 2024 Evidence-Based Clinical Practice Guideline From the American Physical Therapy Association Academy of Pediatric Physical Therapy.

Congenital muscular torticollis (CMT) is a postural condition evident shortly after birth. The 2013 CMT Clinical Practice Guideline (2013 CMT CPG) set standards for the identification, referral, and physical therapy management of infants with CMT, and its implementation resulted in improved clinical outcomes. It was updated in 2018 to reflect current evidence and 7 resources were developed to support implementation. Purpose: This 2024 CMT CPG is intended as a reference document to guide physical therapists, families, health care professionals, educators, and researchers to improve clinical outcomes and health services for children with CMT, as well as to inform the need for continued research. Results/Conclusions: The 2024 CMT CPG addresses: education for prevention, screening, examination and evaluation including recommended outcome measures, consultation with and referral to other health care providers, classification and prognosis, first-choice and evidence-informed supplemental interventions, discontinuation from direct intervention, reassessment and discharge, implementation and compliance recommendations, and research recommendations.

Predictive factors associated with Bile culture positivity And phenotypiCal antIbiogram resistance patterns in patients taken to LaparOscopic cholecystectomy (BACILO): protocol for a prospective observational cohort study and development of a prognostic prediction model.

Bile fluid is aseptic under normal conditions; however, in the presence of cholecystitis, its susceptibility to bacterial colonisation varies, with reported rates of 20%-70% of cases. This process is referred to as bactibilia and/or bacteriobilia and can be considered a secondary complication of biliary stasis and cholecystitis in general. In the management of acute cholecystitis, the antibiotic regimen should be prescribed based on the presumed pathogens involved, taking into consideration the risk factors for resistance patterns according to demographics and local exposure. The aim of this study is to determine the predictive factors for bile culture positivity and antibiotic resistance in patients who underwent laparoscopic cholecystectomy in the Méderi Hospital Network. We hope to develop a predictive model that allows us to better guide antibiotic therapy. This is a prospective observational cohort study with prognostic prediction model. Patients who will undergo laparoscopic cholecystectomy and have bile cultures taken in the Méderi Hospital Network during the study period will be included. The dependent variables will be positive bile culture and antibiotic resistance, and the predictive variables will be age, presence of diabetes, diagnosis of choledocholithiasis, diagnosis of cholecystitis and severity of cholecystitis according to the Tokyo criteria. The minimum sample size has been calculated at 703 patients. Follow-up will continue until a control appointment 15 days after the procedure. The primary outcomes are bile culture positivity and phenotypical antibiogram resistance. For each outcome, a multivariate logistic regression will be performed using frequentist and Bayesian prediction techniques. This study was approved by the Méderi network research department committee (CIMED) and by Universidad del Rosario's Research Ethics Committee (CEI-UR; DVO005 2555-CV1837). Written informed consent is required for participation. The results will be disseminated through the submission of an academic article to a high-impact scientific journal, presentations at academic conferences, and sharing with our institution's faculty to inform antimicrobial therapy management based on local epidemiological data. NCT06314399.

S955 Dual Antiplatelet Therapy Management During Acute Gastrointestinal Bleeding After Percutaneous Coronary Intervention: A Real-World Nationwide Analysis

S955 Dual Antiplatelet Therapy Management During Acute Gastrointestinal Bleeding After Percutaneous Coronary Intervention: A Real-World Nationwide Analysis

EDAPT: The Development And Implementation Of A Novel Referral Pathway From The Emergency Department

Abstract Background The Emergency Department Admission Prevention Therapy (EDAPT) service was developed by Therapy staff of the Pathfinder team in order to facilitate timely and appropriate discharges from the Emergency Department (ED) and to maximise capacity for the follow-up team. The aim of this pilot is to provide rapid access to therapy post discharge from ED for older adults with acute decline in function in order to prevent hospital admission. The service provides a short-term reablement approach within the home aiming to facilitate patients to regain pre-acuity baseline. EDAPT was modelled from an existing service but has now been expanded to accepting direct referrals from ED Medical Staff and Advanced Nurse Practitioners (ANPs) outside of standard working hours. Methods The pilot was introduced following collaboration and consultation with a number of key stakeholders including respective Therapy Managers, ED Consultants, ANPs and ED Therapists. A new EDAPT referral pathway was created, and documentation including specific referral and assessment forms. A designated area for receipt of referrals in the ED department was chosen and checked daily. Results 64 patients with a mean age of 80.5 years were referred to the EDAPT service from November ’23 to April ’24. 53 of those patients received face-to-face input and had a mean Clinical Frailty Scale score of 5. 27% (n=17) of referrals were initiated out-of-hours via Medical and ANP staff and 48% (n=31) of referrals were falls related. Patients received an average of 2 follow-up visits during EDAPT involvement. Conclusion The EDAPT pilot is successfully facilitating timely and appropriate discharges from the ED, improving patient experience and patient flow from ED to their own home. The pilot integrates acute hospital care and community services, supporting a person-centred approach of the right care, at the right time and in the right place.

Genitourinary malignancies in kidney transplant recipients.

Advances in immunosuppressive therapy and postoperative management have greatly improved the graft and patient survival rates after kidney transplantation; however, the incidence of post-transplant malignant tumors is increasing. Post-renal transplantation malignant tumors are associated with renal failure, immunosuppression, and viral infections. Moreover, the risk of developing cancer is higher in kidney transplant recipients than in the general population, and the tendency to develop cancer is affected by the background and environment of each patient. Recently, cancer after kidney transplantation has become the leading cause of death in Japan. Owing to the aggressive nature and poor prognosis of genitourinary malignancies, it is crucial to understand their epidemiology, risk factors, and best practices in kidney transplant recipients. This review has a special emphasis on the epidemiology, risk factors, and treatment protocols of genitourinary malignancies in kidney transplant recipients to enhance our understanding of the appropriate management strategies. Optimal immunosuppressive therapy and cancer management for these patients remain controversial, but adherence to the general guidelines is recommended.

BMP4 and Temozolomide Synergize in the Majority of Patient-Derived Glioblastoma Cultures.

One of the main causes of poor prognoses in patient with glioblastoma (GBM) is drug resistance to current standard treatment, which includes chemoradiation and adjuvant temozolomide (TMZ). In addition, the concept of cancer stem cells provides new insights into therapy resistance and management also in GBM and glioblastoma stem cell-like cells (GSCs), which might contribute to therapy resistance. Bone morphogenetic protein-4 (BMP4) stimulates astroglial differentiation of GSCs and thereby reduces their self-renewal capacity. Exposure of GSCs to BMP4 may also sensitize these cells to TMZ. A recent phase I trial has shown that local delivery of BMP4 is safe, but a large variation in survival is seen in these treated patients and in features of their cultured tumors. We wanted to combine TMZ and BMP4 (TMZ + BMP4) therapy and assess the inter-tumoral variability in response to TMZ + BMP4 in patient-derived GBM cultures. A phase II trial could then benefit a larger group of patients than those treated with BMP4 only. We first show that simultaneous treatment with TMZ + BMP4 is more effective than sequential treatment. Second, when applying our optimized treatment protocol, 70% of a total of 20 GBM cultures displayed TMZ + BMP4 synergy. This combination induces cellular apoptosis and does not inhibit cell proliferation. Comparative bulk RNA-sequencing indicates that treatment with TMZ + BMP4 eventually results in decreased MAPK signaling, in line with previous evidence that increased MAPK signaling is associated with resistance to TMZ. Based on these results, we advocate further clinical trial research to test patient benefit and validate pathophysiological hypothesis.