Safety Of Administration Research Articles

Exploratory study of TAS-102 combined with intermittent administration of fruquintinib in the treatment of third-line metastatic colorectal cancer.

174 Background: Fruquintinib and TAS-102 are two globally recognized standard therapies for mCRC patients who have previously undergone standard chemotherapy. A phase II exploratory study suggested that the combination of TAS-102 and fruquintinib could prolong progression-free survival (PFS) and overall survival (OS) in these patients. However, the benefits are sometimes limited due to tolerability issues associated with continuous dosing. This study aimed to investigate the efficacy and safety of intermittent administration of TAS-102 combined with fruquintinib as a third-line treatment for mCRC patients. Methods: This open-label, single-arm, single-center, exploratory clinical trial enrolled mCRC patients who had failed at least two standard treatment regimens. Eligible patients received oral fruquintinib (3 mg, once daily, on days 1-5 and 8-12) and TAS-102 (35 mg/m², twice daily, on days 1-5) every two weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was objective response rate (ORR). Secondary endpoints included OS, PFS , DCR, and safety. Results: From August 2023 to September 2024, 26 eligible patients were enrolled. The median age of the patients was 58 years (range: 19-77), with 61.5% being female. RAS mutations were present in 57.7% of patients, 57.7% had left-sided colon or rectal cancer, 57.7% had liver metastases, and 76.9% had multiple metastases. As of September 10, 2024, 22 patients had undergone at least one tumor assessment, and 12 patients were still on treatment. Among them, 18.2% (4/22) achieved partial response , and 50% (11/22) had stable disease as the best response. Median PFS (mPFS) was 135 days (95% CI: 60.52-209.48). mPFS in RAS-mutant and RAS wild-type patients was 161 days (95% CI: 63.37-258.63) and 135 days (95% CI: 60.20-209.80), respectively, with ORRs of 25% and 12.5%. mPFS in patients with liver metastases (LM) and non-LM was 135 days (95% CI: 45.42-224.58) and 161 days (95% CI: 87.84-234.16), respectively, with ORRs of 14.3% and 25%. mPFS in patients with multiple metastases was 135 days (95% CI: 71.86-198.14), with an ORR of 17.6%. Median OS was not yet mature. Treatment-related adverse events (TRAEs) were generally manageable and tolerable. The most common hematological TRAEs (any grade, grades 3-4) included leukopenia (76.9%, 11.5%), neutropenia (73.1%, 11.5%), and anemia (53.8%, 7.7%). Non-hematological TRAEs were mostly grades 1-2, including anorexia (46.2%) and fatigue (19.2%). One case of grade 3 hypertension was reported. No treatment-related deaths were observed. Conclusion s: These preliminary results suggest that intermittent administration of TAS-102 in combination with fruquinitinib as a third-line treatment for patients with mCRC reduces hematological toxicity and is well tolerated, with encouraging clinical results. Clinical studies are ongoing. Clinical trial information: ChiCTR2300078241 .

Safety and efficacy of combined intra-articular administration of vancomycin and ε-aminocaproic acid in total hip arthroplasty : a clinical study.

To evaluate the concurrent use of vancomycin and ε-aminocaproic acid (EACA) in primary total hip arthroplasty (THA). In total, 120 patients undergoing unilateral primary THA were divided into three groups: Group VE received intra-articular vancomycin and EACA; Group V received only intra-articular vancomycin; and Group E received only intra-articular EACA. Blood and joint fluids were sampled postoperatively to measure the vancomycin levels using chromatography. Blood loss and kidney function were monitored. Groups E and VE had equivalent blood loss, which was less than that in Group V. Intra-articular vancomycin levels were higher in Group VE at all intervals, with similar serum levels across the groups. Acute kidney injury, ototoxicity, and allergies were not observed, nor was a difference in rates of periprosthetic joint infection. Adding intra-articular EACA to vancomycin did not affect intra-articular vancomycin levels, and maintained EACA's antifibrinolytic effects.

Effects of Isoproterenol Administration in Dobutamine Stress Echocardiography.

This study evaluated the safety and efficacy of isoproterenol administration as an adjunct for achievement of target heart rate (HR) during dobutamine stress echocardiography (DSE). In DSE, optimal accuracy is achieved when a target HR of 85% of maximal predicted heart rate (MPHR) is attained. Although rarely studied, intravenous isoproterenol has been used as an adjunct therapy to dobutamine and atropine to increase chronotropic response during pharmacologic stress testing. We identified 5569 DSE studies during which 264 received isoproterenol at MedStar Georgetown University Hospital from August 2011 to March 2023. Of the studies receiving isoproterenol, we collected clinical and echocardiographic parameters from each study to assess the effects of isoproterenol administration, including downstream events. In 264 examinations with isoproterenol, 169 (64%) achieved 85% MPHR. Among these, 103 (39%) developed premature ventricular contractions, 79 (30%) developed symptoms including nausea/vomiting in 44 (17%), and chest pain in 15 (6%). There was a hypertensive response to stress in 53 studies (20%) and a hypotensive response in 37 studies (14%). There was no significant increase in 30-day and 1-year death when compared to studies that did not receive isoproterenol. Isoproterenol can effectively be used as an adjunctive agent in DSE to achieve the requisite hemodynamic stress for evaluation of ischemia, with a similar rate of side effects and complications compared to dobutamine and atropine stress testing.

Insulin Pen Administration Efficacy and Safety in an Older Patient.

Objective To describe a successful pharmacist-led intervention to effectively and safely provide education and pharmacotherapy management for an older patient with uncontrolled type 2 diabetes mellitus (T2DM) who failed to remove the needle shield on insulin pens for injection. Setting: Family medicine residency clinic. Practice Description: The clinic, part of a major urban health system, consists of 27 medical residents, 15 attending physicians, and 1 ambulatory care pharmacist managing chronic diseases collaboratively. It primarily serves low-income patients in a Midwest city. Practice Innovation: A 93-year-old White female with T2DM, receiving insulin therapy, was referred to the ambulatory care pharmacist by her physician for diabetes management. The patient had been hospitalized recently for hyperosmolar hyperglycemic state with a hemoglobin A1c of 15.9%. The pharmacist identified a failure to remove the needle shield on the insulin pen resulting in ineffective insulin administration, which caused persistent hyperglycemia and subsequent hospitalizations. This also posed a safety concern for severe hypoglycemia if proper administration resumed without adjusting the inflated dosing. The pharmacist used demonstration devices and the teach-back method to provide education and implement pharmacotherapy adjustments, resulting in effective and safe insulin administration. Main Outcome Measurements: Change in diabetes medication regimen, home blood glucose readings including continuous glucose monitor data, hemoglobin A1c results, frequency of hypoglycemic episodes, and number of hospitalizations for T2DM. Results: Over seven months, dose adjustments to basal insulin, combined with proper administration technique and the addition of empagliflozin, resulted in a hemoglobin A1c below 7%, with no severe hypoglycemia or diabetes-related hospitalizations. Conclusion: Medication errors, including insulin administration errors, highlight the need for thorough education in insulin therapy management. Education and monitoring empower older patients to self-manage diabetes safely and effectively, aligning with guidelines. Further research is required to identify optimal strategies for educating older patients on self-managing T2DM with insulin therapy.

Examining the Efficacy, Safety, and Future Prospects of Tirofiban in Managing Myocardial Infarction among Diabetic Patients.

Myocardial infarction (MI) is a leading cause of death worldwide, particularly in patients with diabetes mellitus (DM). Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, has shown promise as adjunctive therapy in the emergency management of MI in diabetic patients. However, a comprehensive understanding of its use, efficacy, safety, and limitations in this patient population is necessary to optimize treatment strategies and improve patient outcomes. This review article utilized a systematic approach to gather relevant research articles, clinical trials, and studies on the use of tirofiban in the therapy of MI in diabetic patients. Databases, such as PubMed and Google Scholar, were extensively searched using specific keywords related to tirofiban, MI, DM, STEMI, and antiplatelet therapy. The collected data were carefully examined, summarized, and analyzed to provide an extensive overview of using tirofiban in the management of MI in diabetic individuals. The analysis of the gathered literature revealed that tirofiban has demonstrated efficacy in improving clinical outcomes, reducing myocardial ischemia-reperfusion injury, and promoting early recovery of heart function in diabetic patients with MI undergoing percutaneous coronary intervention. The fast on- and off-rate and dose-dependent effect of the drug on platelet aggregation contribute to its effectiveness. However, caution should be exercised due to the potential risk of tirofiban-associated thrombocytopenia. Clinical trials and studies have provided evidence- based dosing guidelines, enabling the safe and effective administration of tirofiban in this patient population. Tirofiban, a platelet GP IIb/IIIa receptor inhibitor, shows promise as adjunctive therapy in the emergency management of MI in diabetic patients. It has demonstrated efficacy in improving clinical outcomes, reducing myocardial ischemia-reperfusion injury, and promoting early recovery of heart function. However, healthcare providers should be cautious regarding the potential risk of tirofiban-associated thrombocytopenia. Further research is needed to optimize dosing guidelines, evaluate long-term safety, and fully understand the benefits and limitations of tirofiban in this patient population. The comprehensive insights provided in this review aim to enhance treatment strategies and improve patient outcomes in the emergency management of MI in diabetic individuals.

Assessment of Knowledge, Attitude and Practice among Nurses Regarding Safe Administration of Chemotherapy at Tertiary Care Hospitals of Peshawar

Assessment of Knowledge, Attitude and Practice among Nurses Regarding Safe Administration of Chemotherapy at Tertiary Care Hospitals of Peshawar

The PROPHECI trial: a phase II, double-blind, placebo-controlled, randomized clinical trial for the treatment of pseudoxanthoma elasticum with oral pyrophosphate

Background/aims.Pseudoxanthoma Elasticum (PXE, OMIM 264800) is an autosomal, recessive, metabolic disorder characterized by progressive ectopic calcification in the skin, the vasculature and Bruch’s membrane. Variants in the ABCC6 gene are associated with low plasma pyrophosphate (PPi) concentration. There is currently no reference treatment for this chronic debilitating disease.MethodsPROPHECI (PyROphosPHate supplementation to fight ECtopIc calcification in PseudoXanthoma Elasticum) is the first phase II, randomized, double-blind, placebo-controlled clinical trial (NTC 04868578) to evaluate the efficacy and safety of a daily oral PPi salt supplementation to attenuate and/or stabilize the progression of ectopic calcification in PXE patients. The primary endpoint is the change in arterial calcification volume quantified by non-contrast CT scan between baseline and 12 months of treatment. Secondary endpoints include the safety and efficacy of daily oral PPi administration on ocular and skin lesions and the evaluation of patients’ quality of life.DiscussionThe PROPHECI trial aims to provide safety and efficacy data on the use of daily oral PPi to reduce or stabilize ectopic calcification in PXE. It also aims to validate the best markers to include in the design of future trials for the treatment of PXE and other parent diseases.Trial registrationTrial registration number: NCT 04868578.References can be found on the ClinicalTrials.gov website: https://clinicaltrials.gov/study/NCT04868578?cond=Pseudoxanthoma%20Elasticum&intr=pyrophosphate&rank=2

P-1419. Vaccine failure of the live-attenuated vaccine after liver transplantation depends on the vaccine strain

Abstract Background A recent conditional recommendation suggests considering live-attenuated vaccines for solid organ transplant recipients, yet the conditions of their safe and effective administration remain unclear. Primary vaccine failures after the first dose of live-attenuated vaccines (measles, rubella, and mumps) were significantly different between the vaccine strains. Methods This prospective study, conducted at Keio University Hospital from 2002 to August 2023, gave live-attenuated vaccines to liver transplant (LT) recipients fulfilling the criteria for live-attenuated vaccines, including humoral and cell-mediated immunity. Patient background information, immunization date, vaccine strain, immunosuppressive agents at the time of vaccination, and antibody titers were collected. Factors related to primary and secondary vaccine failure were evaluated to enhance the effectiveness of the live-attenuated vaccine program after LT. Kaplan–Meier curves for the proportion of remaining positive antibody titer after the first dose of indicated live-attenuated vaccine for post-liver transplant recipients. Results Among 67 LT recipients, 54, 55, 47, or 55 received at least one dose of live-attenuated vaccine for measles, rubella, varicella, or mumps, respectively. Measles vaccine with the AIK-C strain exhibited significantly lower primary failure rates than the CAM-70 strain (1/38 vs. 4/16, odds ratio: 0.08, 95% confidence interval [CI]: 0.01–0.80, p = 0.02) (Table 1). No primary failures were observed with the TO-336 strain of rubella, whereas 4 of 10 LT recipients with the Matsuura strain of rubella did not seroconvert. For mumps, the Hoshino strain showed lower primary failure rates than the Torii strain (15/52 vs. 3/3, p = 0.03). Among seroconverted LT recipients after the first dose of live-attenuated vaccine, the proportion of remaining positive antibody titer is shown by Kaplan–Meier curves (Figure 1). In the years following the first doses of measles, varicella, and mumps vaccines, the proportion of remaining positive antibody titers decreased gradually. Furthermore, the AIK-C strain exhibited a significantly lower risk of secondary vaccine failure compared to the CAM-70 strain (hazard ratio: 0.29, 95% CI: 0.12–0.72, p = 0.01) (Figure 2). Kaplan–Meier curves for the proportion of remaining positive antibody titer after the first dose of measles vaccine for post-liver transplant recipients with Log-rank test for the vaccine strains. Conclusion Vaccine strains are the most critical factor influencing primary and secondary vaccine failure in post-transplant live-attenuated vaccination. Disclosures Masayoshi Shinjoh, MD, PhD, Meiji Seika Pharma Co., Ltd: Honoraria|Mitsubishi Tanabe Pharma Corporation: Honoraria|MSD K.K.: Honoraria|Pfizer Japan Inc: Advisor/Consultant|Shionogi & Co., Ltd: Honoraria

P-343. The Feasibility of Safely and Efficiently Administering Antivirals to Nursing Home Residents During COVID-19 Outbreaks is Impaired by Polypharmacy and Comorbidities

Abstract Background Due to congregate living, advanced age, and frailty, nursing home (NH) residents are at high risk for infections caused by respiratory viruses. Protocols for the efficient and safe administration of antivirals for the treatment and prophylaxis of influenza among NH residents are well-established. Similar protocols for COVID-19 are foreseeable. Use of nirmatrelvir/ritonavir, associated with improved outcomes in high-risk patients with COVID-19, requires careful examination of concomitant medications, renal function, and blood pressure. Here, we explore the potential to administer nirmatrelvir/ritonavir safely and efficiently to NH residents in response to COVID-19 outbreaks. Maximum Severity of Drug Interaction with nirmatrelvir/ritonavir The percentage of NH patients taking at least one medication within 14 days of the census date is categorized by the maximum severity of drug interaction with nirmatrelvir/ritonavir. Methods We studied residents of NHs within the Veterans Health System at four census dates in 2021-2022. We assessed residents’ medications over the prior 14 days, the most recent estimated glomerular filtration rate (eGFR), and vitals for each date. We calculated the proportion of residents with and without potential interactions between their medication regimen and nirmatrelvir/ritonavir. We also determined the proportion of residents with conditions that require dosing adjustments or exacerbate drug interactions such as renal impairment and hypotension. eGFR Values among Nursing Home Patients Renal function is represented as the percentage of NH patients at each census date categorized by eGFR values. Results The median number of distinct drugs per NH resident in the prior 14 days was 13 (IQR: 10-17). Among the >99% of residents with at least one medication administered 14 days before each census date, 88% received at least one agent with an interaction or contraindication with nirmatrelvir/ritonavir (Figure). Among the 50 most commonly prescribed medications, 7 required significant dose modifications. At all 4 census dates, ≥25% of NH residents received atorvastatin, tamsulosin, or amlodipine. Similarly, ≥25% of residents had eGFR < 60mL/minute and 9-10% had blood pressure < 90/60 mmHg. Hypotension Percentages among Nursing Home Patients Each bar represents the percentage of NH patients with hypotension at that census date. Blood pressure analysis was used to determine hypotension with a threshold value of <90/60 mmHg. Conclusion The prevalence of polypharmacy and renal impairment among NH residents challenges the widespread administration of nirmatrelvir/ritonavir as a safe and efficient measure during COVID-19 outbreaks. Clinical decision support tools embedded within electronic health records may help mitigate these risks, as will the availability of effective antiviral agents with fewer drug-drug interactions. Disclosures Federico Perez, MD, MS, Merck: Grant/Research Support Robin Jump, MD, PhD, Abacus: Grant/Research Support|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support

Assessing Preferences of Patients with Chronic Spontaneous Urticaria for Injectable Treatment Profiles.

In the context of injectable biologic products approved or in development for chronic spontaneous urticaria (CSU), it is important to capture which treatment attributes matter most to patient and what trade-offs patients are willing to make. The CHOICE-CSU study aimed to quantify patient preferences toward injectable treatment attributes among patients with CSU, inadequately controlled by H1-antihistamines. This was a two-phase cross-sectional patient preference study in adult patients with a diagnosis of CSU, inadequately controlled by H1-antihistamines. A qualitative phase collected patients' insights and relevant treatment attributes that mattered to them, and the outputs were used for the quantitative phase to create the actual injectable treatment profiles with attributes and levels such as: efficacy, safety, and mode of administration. The quantitative phase used discrete choice experiment (DCE) methodology. Eligible patients were asked to make hypothetical choices between 12 treatment profile pairs, created by Sawtooth SoftwareTM. The DCE data were analyzed using hierarchical Bayesian logistic regression models, enabling the quantification of the relative importance of each attribute/level during the decision-making process. A total of 450 respondents participated in the DCE. The key attributes driving respondent preference amongst injectable treatment options were type of administration device (relative importance 18.5%), complete control of urticaria (relative importance 17.4%), and resolution of angioedema (relative importance 16.4%). Keeping all other attributes and levels equal, the predicted choice share was higher for a profile with an auto-injector versus one with a pre-filled syringe (72.9% versus 27.1%). The CHOICE-CSU study is the first study to provide a quantitative assessment of preferences that patients with CSU, inadequately controlled by H1-antihistamines, have for injectable treatment attributes. Symptom-free periods are the most important overriding therapy goal for patients, and patients will accept some inconveniences, such as administration mode, to achieve this. Additionally, when efficacy is equivalent, administration ease of injectable therapies is valued by patients. As new CSU oral treatment options emerge, additional testing of patient preference toward oral treatments will be required.

Umbilical Cord-derived Mesenchymal Stem Cells (CLV-100) Infusion in Healthy Subjects: a 5-Year Follow-up Study on Safety and Immunomodulatory Effect

Abstract Purpose Umbilical cord-derived mesenchymal stem cells (UCMSCs) have garnered significant attention in the field of regenerative medicine, specifically in inflammation-related diseases. Our team has previously demonstrated that a single infusion of allogeneic UCMSCs by Cytopeutics® (CLV-100), at both low dose (65 million cells) and high dose (130 million cells), in 11 healthy volunteers was safe up to 6 months with a dose-dependent immunomodulatory effect. In this present follow-up study, we investigated the medium-term safety and efficacy of intravenous administration of CLV-100 in the same healthy subjects. Methods All 11 subjects were enrolled in this 5-year follow-up, and none dropped out (NMRR-13–1152-17400, 28/09/2016). Clinicians conducted consultations to assess overall health indicators. Blood samples and serum were collected for laboratory testing and biomarker analysis, respectively. Results Five years after the CLV-100 infusion, all subjects remained healthy, with no reported side effects or major health conditions. Levels of cancer markers also remained within normal ranges. The anti-inflammatory effect of CLV-100 remained statistically significant in the high-dose group. Notably, major organ health parameters, including those subjects aged over 60 years, remained stable even after 5 years. Conclusion The findings demonstrated the medium-term safety of a single CLV-100 infusion and persistent dose-dependent immunomodulatory effects. CLV-100 may also confer protection against age- and inflammation-related frailty. Lay Summary The current follow-up study provides insight into the safety and immunomodulatory effects of a single infusion of allogeneic umbilical cord-derived mesenchymal stem cells (CLV-100) for up to 5 years in healthy subjects. The effects on the inflammatory cytokines CLV-100 were more pronounced in the high-dose group. In addition, other biomarker levels were comparable between the older and younger age groups. CLV-100 is therefore safe over the medium-term with sustained anti-inflammatory effect in a dose-dependent manner.

A detoxified TLR4 agonist inhibits tumour growth and lung metastasis of osteosarcoma by promoting CD8+ cytotoxic lymphocyte infiltration

BackgroundOsteosarcoma is the most common malignant bone tumour with limited treatment options and poor outcomes in advanced metastatic cases. Current immunotherapies show limited efficacy, highlighting the need for novel therapeutic approaches. Systemic immune activation by Toll-like receptor 4 (TLR4) immunostimulants has shown great promise; however, current TLR4 agonists’ toxicity hinders this systemic approach in patients with osteosarcoma.MethodsWe compared the antitumour effect of lipopolysaccharides (LPS) with that of an innovative chemically detoxified TLR4 agonist (Lipo-MP-LPS) in a syngeneic metastatic osteosarcoma mouse model. Lipo-MP-LPS exhibited an optimal safety and solubility profile for systemic administration at an effective dose. We evaluated tumour growth, lung metastases, and immune cell infiltration in wild-type and TLR4-mutant mice and performed selective immunodepletion.ResultsLipo-MP-LPS exhibited antitumour effects against localised osteosarcoma tumours and lung metastases, like those of natural LPS. Lipo-MP-LPS promoted CD8+ T cells and M1 macrophages infiltration in primary tumours and CD8+ T cells in metastases, with an M1-phenotype macrophage shift. The Lipo-MP-LPS antitumour effects were found to depend on TLR4 and CD8+ T cells, but not on macrophages.ConclusionLipo-MP-LPS inhibited tumour growth and lung metastasis of osteosarcoma by promoting CD8 + T cell infiltration, indicating its therapeutic potential for advanced osteosarcoma.

Competencies of nurses to participate in safe medication management practices for biologics: A scoping review.

To review the existing literature relating to nurse competence in safe medication management practices for biologics, identify evidence, and develop a competency framework to clarify the role of nurses in these practices. With the widespread use of biological agents in disease treatment, ensuring the safe and economical use of high-cost medicines is particularly important. Even though nurses are essential in patient care, detailed knowledge regarding their competence and role in the safe administration of biologics is lacking. A scoping review was performed following the methodology of Arksey and O'Malley and the PRISMA ScR guidelines. Electronic databases, including PubMed, CINAHL, Embase, Scopus, and Web of Science, were searched using accepted keywords, and relevant articles were identified using inclusion and exclusion criteria. A total of 3,422 studies were retrieved, 24 of which were eligible for inclusion. The required competencies for nurses were summarized into six areas: clinical specialized knowledge, critical thinking and problem-solving skills, safe medication skills, health education skills, communication and coordination skills, and technological literacy. We provide insights into the competencies of nurses involved in the safe medication management of biologics. These competencies can be used to assess the actual competency level of nurses and facilitate the maximization of biological treatment goals and outcomes. This plays a vital role in optimizing the use of healthcare resources and demonstrating outcomes.

Lipid nanoparticle-mediated intracameral mRNA delivery facilitates gene expression and editing in the anterior chamber of the eye.

Lipid nanoparticles (LNPs) have shown great potential in the field of gene therapy for retinal diseases. To expand on this application, we investigated LNP-mediated mRNA delivery to the anterior chamber of the eye via the intracameral (IC) route of administration. Here, we show that IC injections of LNPs facilitated protein expression and gene editing in the trabecular meshwork (TM). Administration of Cre-mRNA LNPs to Ai9 mice resulted in robust tdTomato expression in the angle and corneal endothelium. In C57BL/6 mice, mCherry-mRNA LNPs demonstrated localized protein expression in the TM, which peaked at 72 h and subsequently declined over 120 h. Additionally, LNPs encapsulating Cas9 mRNA with sgAi9 enabled in vivo gene editing in Ai9 mice, with up to 14.3 % editing efficiency. This induced tdTomato expression in the iridocorneal angle, validating the potential of LNPs for gene editing applications. Importantly, no ocular toxicity was observed, indicating the safety of the IC LNP administration. Our findings highlight the use of LNPs for targeted gene therapy and editing, paving the path for the treatment of diseases such as glaucoma in the anterior eye.

Joint Optimization of Antenna System Matching and Specific Absorption Rate Focusing in Microwave Hyperthermia Cancer Treatment

Objective: Microwave hyperthermia is a clinically proven cancer treatment used in combination with conventional therapies to enhance the overall treatment outcome. It consists in selectively increasing the temperature of tumor cells to 40–44 °C by means of electromagnetic fields that are externally generated and coupled to the patient body via antenna applicators. The primary goal is to shape the power deposition (specific absorption rate, SAR) with focusing on the tumor region, and minimizing the risk of hotspots in the surrounding healthy tissues. Methods: For non-superficial tumors, phased-array antennas are used to focus the energy on the tumor. Finding patient-specific optimal antenna feeding coefficients represents an essential step to ensure an effective and safe administration of the heating. In this article, we present a way to optimize the array power transfer effectiveness (impedance matching) that does not deteriorate the spatial power deposition performance. A global optimization approach is adopted, using a cost function properly tailored to incorporate the active reflection coefficients of the array and the Hotspot-to-Target SAR Quotient (HTQ)—the latter being the standard in hyperthermia applications. Results: The effectiveness of the technique is demonstrated in a scenario relevant to the treatment of tumors in the neck region. The results show that our method significantly improves antenna matching without compromising the HTQ, achieving values within the recommended limits. The performance of the proposed approach is also experimentally tested with full heating in a corresponding phantom. Conclusions: This study introduces an optimization approach that enhances phased-array antenna performance for hyperthermia treatments without affecting spatial power deposition.

Development and validation of a sensitive LC-MS/MS assay for determination of upadacitinib in human plasma and its application in patients with inflammatory bowel disease.

Upadacitinib is a selective Janus kinase (JAK) 1 inhibitor approved by the Food and Drug Administration for the treatment of moderate-to-severe inflammatory bowel disease (IBD). We aimed to establish and validate a method for determining Upadacitinib in patients with IBD by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The mobile phase was 0.1 % formic acid: acetonitrile (35:65, v/v) at a flow rate of 0.40 mL/min. Upadacitinib and its internal standard Upadacitinib 15N, d2 were separated by a Waters Xbridge BEH C18 column (4.6 × 100 mm, 2.5 μm) and subjected to mass analysis using positive electrospray ionization (ESI). The calibration range of Upadacitinib was 0.5-200 ng/mL with the correlation coefficient r2 ≥ 0.99. Accuracies ranged from -9.48 % ~ 8.27 % and the inter- and intra-day precisions were less than 15 % for all analytes in quality control samples. There was no significant matrix effect. The range of extraction recoveries was 87.53-93.47 % for all analytes. Twenty-one plasma samples were obtained from the sixth affiliated hospital of Sun Yat-sen University. The median plasma concentration of Upadacitinib was 7.32 (0.56-26.78) ng/mL. This newly developed method is sensitive, simple, and successfully applied in determining Upadacitinib in IBD patients to provide reference for safe and effective drug administration in clinical practice.

An anonymized, de-identified registry study protocol to determine the effectiveness and safety of weight loss with enavogliflozin in patients with type 2 diabetes mellitus.

Sodium-glucose co-transporter 2 inhibitors, such as enavogliflozin, offer promising metabolic benefits for patients with type 2 diabetes (T2D), including glycemic control and improved cardiac function. Despite the clinical evidence, real-world evidence is needed to validate their safety and effectiveness. This study aims to evaluate the effects of weight loss and safety of enavogliflozin administration in patients with T2D in a real-world clinical setting over 24 weeks. This is a large-scale, prospective, multicenter, non-interventional observational study and will be conducted in 12 primary care centers nationwide between 2024 and 2026. Data will be collected at baseline, 12 weeks, and 24 weeks in a real-world clinical setting, including demographic details, clinical history, lifestyle habits, medication use, and various health indicators. Eligible participants are adults aged 19 to 80 with T2D and a body mass index (BMI) of ≥23 kg/m2 who are currently receiving treatment with Envlo (enavogliflozin) or Envlomet (enavogliflozin/metformin) tablets or planning to start treatment. The primary outcome is the change in BMI and body weight at 24 weeks from baseline. Secondary outcomes evaluated are changes in BMI and weight at 12 weeks, the proportion of participants achieving significant reductions in BMI and weight at 12 and 24 weeks, and body composition and glycemic improvements at 12 and 24 weeks. The study will analyze shifts in lipid profiles, liver and kidney functions, and body composition at 12 and 24 weeks as exploratory outcomes. For safety outcomes, the trial will prioritize the monitoring of adverse drug reactions and specific events of interest such as hypoglycemia, urinary tract infections, genital infections, polyuria, and polydipsia. This study design enables us to evaluate the effectiveness and safety of enavogliflozin for weight loss in a real-world setting while exploring its potential positive effects on cardiac function and metabolic risk factors in overweight or obese patients with T2D.

P0669 Safety of intravenous and subcutaneous guselkumab induction administration: Results from the GALAXI and GRAVITI studies in participants with Crohn’s Disease

Abstract Background Guselkumab (GUS) is a dual-acting IL-23 inhibitor that potently neutralizes IL-23 and binds to CD64, a receptor on cells that produce IL-23. Induction with both intravenous (IV) and subcutaneous (SC) GUS was effective in phase 2/3 clinical trials of participants (pts) with moderately to severely active Crohn’s disease (CD). To characterize the safety of GUS IV and SC induction regimens, we evaluated safety data from clinical trials of GUS in CD. Methods We evaluated data from phase 2/3 CD studies with IV induction (GUS 200mg IV q4w in GALAXI 1, 2, and 3) and SC induction (GUS 400mg SCq4w in GRAVITI) to assess rates of safety events (proportions of pts with ≥1 event) during the induction period (Week 0-12). Results During the induction period, rates were not higher in either the IV or the SC groups than the respective placebo (PBO) groups for adverse events (AEs), serious AEs, or AEs leading to discontinuation (Table 1). Serious infections occurred in 1 pt in the GUS IV group and 1 pt in the GUS SC group; neither led to discontinuation of study treatment. No serious infections were reported in PBO-treated pts in either group. Of the 1376 GUS SC injections during the induction period in GRAVITI, 6 (0.4%) were associated with injection site reactions, which included pruritus, erythema, and swelling. Injection site reactions beyond the induction period with GUS SC in GALAXI and GRAVITI remained low (≤1%) and were comparable regardless of induction administration route. No cases of active tuberculosis, anaphylaxis, serum sickness reactions, major adverse cardiovascular events, or venous thromboembolism were reported during the induction period. In the IV induction group, 1 opportunistic infection (esophageal candidiasis) was reported in a PBO-treated pt and 2 were reported in GUS-treated pts (cytomegalovirus infection and esophageal candidiasis). In the SC induction group, 1 opportunistic infection of esophageal candidiasis was reported in a PBO-treated pt and 0 were reported in GUS-treated pts. One malignancy (basal cell carcinoma) not leading to discontinuation was reported in a pt in the GUS 400 mg SC group. One death was attributed to a non-suicidal (not self-inflicted) gunshot wound in a pt treated with GUS SC. Clinically significant hepatic disorders were reported in 2 pts in the GUS 200mg IV group (1 SAE and 1 AE that led to discontinuation) and 1 pt in the GUS 400mg SC group (1 AE that led to discontinuation) during the induction period. All cases were confounded by additional diagnoses or concomitant medications. Conclusion Both IV and SC induction demonstrated comparable safety results consistent with the well-characterized GUS safety profile. No new safety concerns were identified.

Early dual antiplatelet therapy (DAPT) administration within 6 h post-coronary artery bypass grafting (CABG): an audit, pilot study, and follow-up analysis

BackgroundThe optimal timing for administering dual antiplatelet therapy (DAPT) post-coronary artery bypass grafting (CABG) remains a subject of debate. This study aimed to evaluate the safety and efficacy of early DAPT administration within 6 h post-CABG, following the implementation of a new standard operating procedure (SOP). This study was conducted in three phases at the National Heart Institute of Malaysia. Phase 1 involved a clinical audit of 80 isolated CABG patients to evaluate current DAPT practices. Phase 2 was a pilot study involving 320 patients to establish criteria for early DAPT initiation. Phase 3 comprised a prospective cohort analysis comparing outcomes between 939 propensity-matched pairs receiving early/new SOP (< 6 h) and late/old SOP (> 6 h) DAPT.ResultsThe clinical audit revealed a mean DAPT administration time of 18.3 h post-CABG, highlighting variability in practice. The pilot study demonstrated that early DAPT was associated with a significantly lower chest reopening rate (0.8% vs. 21.6%) under stringent selection criteria. In the follow-up study, early DAPT was linked to reduced rates of postoperative stroke (1.0% vs. 2.5%, p = 0.013), dialysis (5.5% vs. 7.0%, p < 0.001), and chest reoperation (6.5% vs. 9.0%, p = 0.045). Despite a higher transfusion rate in the early DAPT group (76.0% vs. 43.6%, p < 0.001), ICU stays and hospitalization durations were not prolonged. Mortality rates were lower in the early DAPT group (3.2% vs. 4.6%), although the difference was not statistically significant (p = 0.123).ConclusionsGuided by stringent clinical criteria, early DAPT administration within 6 h post-CABG is a feasible and effective strategy for reducing adverse outcomes, such as stroke and dialysis requirements, while maintaining manageable bleeding risks. Future research should explore long-term graft patency, refine transfusion protocols, and assess the broader applicability of this approach.

Stability study of topotecan in ophthalmic prefilled syringes for intravitreal delivery

BackgroundIntravitreal and intracameral administration of melphalan and topotecan (TPT) has shown its efficacy in the treatment of retinoblastoma over the last few years. Due to rapid hydrolysis, melphalan must be...