Repeated Treatment Research Articles

Pharmacological mechanisms involved in the diuretic activity of the ethanol-soluble fraction of Baccharis milleflora (Less.) DC. - An ethnopharmacological investigation

Ethnopharmacological relevanceBaccharis milleflora (Less.) DC. is a plant native to Brazil that is frequently used in traditional medicine as a diuretic and antihypertensive. However, even though it is traditionally used for these purposes, its diuretic and hypotensive effects have not been fully elucidated. AimInvestigate the cardiorenal effects of the ethanol-soluble fraction (ESBM) of Baccharis milleflora in normotensive rats. Materials and methodsCladodes of B. milleflora were analyzed using light and scanning electron microscopy to provide anatomical data to support quality control. Subsequently, the ESBM was obtained and analyzed using LC-DAD-MS, and its components were annotated. The acute toxicity of ESBM was assessed in female Wistar rats. The acute and prolonged diuretic and hypotensive effects were then studied in Wistar rats. Finally, we assessed the mechanisms responsible for the diuretic effects of ESBM, including the activity of renal Na+/K+/ATPase, angiotensin-converting enzyme, and erythrocyte carbonic anhydrase. Additionally, we also investigated the involvement of bradykinin, prostaglandins, and nitric oxide. ResultsFrom LC-DAD-MS data, thirty-three metabolites were identified from ESBM, including chlorogenic acids, glycosylated phenolic derivatives, C-glycosylated flavones, and O-glycosylated flavonols. No signs of acute toxicity were observed in female rats. The findings showed that ESBM had significant diuretic and natriuretic effects, as well as a potassium-sparing effect. The treatment with ESBM was able to significantly decrease serum levels of creatinine and malondialdehyde, and also significantly increase levels of nitrite, an indirect marker of nitric oxide bioavailability. Furthermore, pre-treatment with L-NAME abolished all diuretic effects induced by ESBM. ConclusionThis study presented important morpho-anatomical and phytochemical data that support the quality control of Baccharis milleflora. The ESBM exhibited a significant diuretic and natriuretic effect following acute and seven-days repeated treatment in Wistar rats, without affecting renal potassium elimination. These effects appear to be dependent on the activation of the nitric oxide-cyclic GMP pathway. This study suggests the potential use of B. milleflora preparations in clinical situations where a diuretic effect is needed.

Comparative study between hyaluronic acid & platelet rich plasma in treatment of knee osteoarthritis

: Knee osteoarthritis (OA) is a prevalent degenerative joint condition. This study aims to compare the therapeutic potential of Hyaluronic Acid (HA) and Platelet Rich Plasma (PRP) in its management.: A comparative study was conducted with patients receiving either HA or PRP injections. Outcome measures included VAS and WOMAC scores, safety profiles, patient satisfaction, and requirement for repeat injections.: PRP-treated patients exhibited superior improvement in VAS and WOMAC scores by the 12-month mark. Adverse reactions were minimal and comparable between groups. Notably, 92% of PRP recipients expressed a willingness for repeat treatment. PRP-treated patients also showcased prolonged therapeutic benefits, with fewer requiring subsequent injections.: PRP outperforms HA in multiple domains, emphasizing its potential as a more effective treatment for knee OA.

P-160 Repeated treatment with the same sperm donor during the second cycle does not improve pregnancy rate, live birth rate nor risk of miscarriage

Abstract Study question Can repeated treatment with the same sperm donor in intrauterine insemination (IUI) and IVF/ICSI in the second cycle improve the outcome? Summary answer Pregnancy rate, live birth and miscarriage were not affected by repeated treatment with the same sperm donor in the second cycle with IUI or IVF/ICSI. What is known already Women with a longer exposure to paternal antigens have a higher chance of successful placentation and the use of donated gametes increases the risk for disorders related to placental insufficiency. Local exposure to seminal fluid has been shown to improve pregnancy rate. However, it is unknown how repeated exposure to the same donor, as opposed to changing donor, affects the outcome and currently there is no evidence suggesting that one method is superior to the other. Study design, size, duration This is a retrospective cohort study from three IVF clinics in Sweden including 868 women who have undergone reproductive treatments with donated sperms between 2014 and 2022. The outcomes pregnancy rate, live birth rate and risk of miscarriage were compared between women who had used the same donor in the second treatment cycle with women who were treated with a new donor. Participants/materials, setting, methods 631 nulliparous women undergoing IUI or IVF/ICSI with donated sperm using the same donor during two consecutive treatment cycles were compared to 237 nulliparous women who had changed donor between the treatments. All medical indications for treatment were included in the study. Oocyte donation cycles and frozen embryo transfer cycles were excluded. Statistical analyses were performed using logistic regression, adjusting for year of treatment, maternal age, treatment method and clinic. Main results and the role of chance No differences in pregnancy rate nor live birth rate were found when comparing repeated treatments with the same donor with change of donor in IUI or IVF/ICSI (odds ratio (OR); 0.95, 95% CI 0.67-1.34, p = 0.77; OR 1.30, 95% CI 0.86-1.95, p = 0.21 respectively). A significant difference was found in miscarriage (OR 0.38, 95% CI 0.18-0.79, p = 0.01). However, after adjusting for year of treatment, maternal age, treatment method and clinic, no significant differences were found in any of the outcomes: pregnancy rate (adjusted OR (aOR) 0.94, 95% CI 0.65-1.38, p = 0.77), live birth rate (aOR 1.21, 95% CI 0.78-1.88, p = 0.40) nor miscarriage (aOR 0.44, 95% CI 0.19-1.03, p = 0.06). Limitations, reasons for caution In addition to the retrospective study design, the restricted number of patients is a limitation. The possibility of undocumented confounders that could impact the results is also a reason for caution. Furthermore, as only two subsequent treatments were studied, any effect of longer exposure could not be evaluated. Wider implications of the findings Our results could not show that using the same sperm donor repeatedly is superior to changing donor regarding pregnancy, live birth or miscarriage. Further research on additional exposure to the same donor as well as outcomes specific to placental insufficiency is needed to address the issue further. Trial registration number NA

Clinical Characteristics and Cycle Thresholds Among Discordant and True Positive Test Results for Clostridiodes difficile

Background: The diagnosis of Clostridioides difficile infection (CDI) is challenging. Despite guideline-directed, multistep testing algorithms and diagnostic stewardship, the treatment of C. difficile colonization persists. The testing algorithm at our system utilizes an initial real-time PCR test (PCR) for Toxin B gene, which if positive, reflexes to an enzyme immunoassay (EIA) for detecting Toxins A and B. Discordant results (PCR +/EIA -) are suggestive of colonization, but the majority of patients with discordant results are treated for CDI. Correlation of C. difficile EIA B polymerase chain reaction (PCR) cycle thresholds (Ct) with the presence of free EIA and disease severity has been observed, but the ability to use Ct in the decision to treat patients with discordant results is unclear. Our study assesses if Ct values and other clinical characteristics favor treatment in select patients with discordant Methods: A retrospective chart review was performed of adult patients (≥ 18-year-old) with positive C. difficile PCR results that were admitted to our health system between June 01 and August 31, 2023. C. difficile PCR and Ct results were obtained by Cepheid GeneXpert and Toxin A and B EIA results were obtained by Meridian Bioscience Immunocard. Patients with discordant (PCR+/EIA) and true positive (PCR+/EIA+) results were compared. We assessed demographics, past medical history, clinical characteristics, severity of illness, PCR Ct values, treatment, and clinical outcomes including: 30-day all-cause mortality and re-admission, and 60-day CDI repeat testing and treatment. Results Of the 122 patients identified, 89 patients had discordant results and 43 had true positive Results: Severity of illness and other clinical and laboratory characteristics were similar between both groups. Mean Ct values were significantly lower for true positive results compared to discordant results, 24.28 vs 29.27, respectively (p26 (p=.08). Of the patients with discordant results, 73 completed treatment for CDI and no difference in clinical outcomes was observed compared to patients with discordant results that were not treated. Conclusion Ct values were lower among patients with true positive results compared to patients with discordant Conclusion: There were no statistically significant different rates of severe or fulminant CDI among patients with discordant results and Ct values < 26, although this finding may be limited by sample size and Ct may be helpful in deciding which discordant patients to treat.

Evaluation of Anxiety Levels in Patients Undergoing Intravitreal Injection for Diabetic Macular Edema

Objective: In this study, we aimed to analyze the anxiety levels of patients regarding intravitreal injection (IVI) using the Amsterdam Preoperative Anxiety and Information Scale (APAIS) and to evaluate the effect of repeated injections on anxiety levels. Methods: Between September 01, 2023 and January 10, 2024, 85 patients who underwent intravitreal anti-vascular endothelial growth factor injection for diabetic macular edema in our clinic were included in this study. Results: According to APAIS scores, mean anesthesia anxiety was 5.4±2.6, surgical anxiety was 5.1±2.6 and total anxiety score was 10.5±3.7. Anesthesia information need was 2.7±0.95, surgical information need was 2.6±1.14 and total information need score was 5.3±1.50. There was no significant difference between genders in terms of total and subgroup scores (p>0.05, all). No significant correlation was found in the correlation analysis between age and number of injections and APAIS scores (subdimensions and total) (p>0.05, all). Conclusion: In conclusion, the potential anxiety of patients before and during intravitreal injection should be considered. In addition, since IVI often involves repeated treatments, it is of great importance to identify modifiable factors that may reduce anxiety. Given the importance of compliance, premedication may be considered to reduce anxiety, especially in high-risk (high preoperative anxiety) patients. Comprehensive explanations about treatment and well-structured processes are crucial for long-term adherence to anti-VEGF therapy.

Repeat treatment of organotypic airway cultures with ethyl methanesulfonate causes accumulation of somatic cell mutations without expansion of bronchial-carcinoma-specific cancer driver mutations

The human in vitro organotypic air-liquid-interface (ALI) airway tissue model is structurally and functionally similar to the human large airway epithelium and, as a result, is being used increasingly for studying the toxicity of inhaled substances. Our previous research demonstrated that DNA damage and mutagenesis can be detected in human airway tissue models under conditions used to assess general and respiratory toxicity endpoints. Expanding upon our previous proof-of-principle study, human airway epithelial tissue models were treated with 6.25–100 µg/mL ethyl methanesulfonate (EMS) for 28 days, followed by a 28-day recovery period. Mutagenesis was evaluated by Duplex Sequencing (DS), and clonal expansion of bronchial-cancer-specific cancer-driver mutations (CDMs) was investigated by CarcSeq to determine if both mutation-based endpoints can be assessed in the same system. Additionally, DNA damage and tissue-specific responses were analyzed during the treatment and following the recovery period. EMS exposure led to time-dependent increases in mutagenesis over the 28-day treatment period, without expansion of clones containing CDMs; the mutation frequencies remained elevated following the recovery. EMS also produced an increase in DNA damage measured by the CometChip and MultiFlow assays and the elevated levels of DNA damage were reduced (but not eliminated) following the recovery period. Cytotoxicity and most tissue-function changes induced by EMS treatment recovered to control levels, the exception being reduced proliferating cell frequency. Our results indicate that general, respiratory-tissue-specific and genotoxicity endpoints increased with repeat EMS dosing; expansion of CDM clones, however, was not detected using this repeat treatment protocol. DisclaimerThis article reflects the views of its authors and does not necessarily reflect those of the U.S. Food and Drug Administration. Any mention of commercial products is for clarification only and is not intended as approval, endorsement, or recommendation.

Comprehensive Treatment of Knee Osteoarthritis Pain through Cryoneurolysis: A Promising Approach for Deep and Superficial Genicular Nerve Modulation - Case Report

Background Knee osteoarthritis is a prevalent and debilitating condition characterized by joint pain, stiffness, and limited mobility. Conventional non-operative treatment approaches often do not provide adequate relief of the patient’s symptoms. Cryoneurolysis of the superficial genicular nerves is a growing and accepted technique used to treat knee pain, however, there is limited literature demonstrating the effectiveness of treating both the superficial and deep genicular nerves, as well as the use of subsequent repeat treatments. Case Report This case study reports on a 65 year-old male with Kellgren-Lawrence grade 2-3 tricompartmental bilateral knee osteoarthritis who underwent cryoneurolysis of the superficial and deep genicular nerves with the iovera° cryoneurolysis device followed by two subsequent repeat cryoneurolysis treatments. Conclusion The results demonstrated a complete resolution of the patient’s pain and enhanced quality of life following cryoneurolysis. Furthermore, subsequent repeat treatments sustained the pain reduction, offering the patient an extended period of improved mobility and reduced discomfort. This case study demonstrates that cryoneurolysis holds promise as a valuable addition to the armamentarium of interventions available for managing knee pain and improving the quality of life for patients suffering from osteoarthritis when they are unable or decide not to pursue surgical intervention.

Cancer nuclear envelope rupture and repair in taxane resistance

Abstract Taxanes, including paclitaxel, docetaxel, and cabazitaxel, are key agents in cancer treatment, often used as front-line chemotherapy drugs in combination with other agent(s) (commonly carboplatin) and as second-line treatments alone. Generally, taxanes are highly effective, but drug resistance unavoidably develops following repeated treatment. Taxanes work by binding to and stabilizing microtubules, leading to mitotic arrest, mitotic catastrophe, and micronucleation. The long-recognized mechanisms of drug resistance generally can be classified into three categories: drug efflux, microtubule polymerization, and apoptotic pathway. A recent new addition to this list is a mechanism related to the nuclear envelope, as cancer cells undergo micronucleation and nuclear membrane rupture when treated with taxanes. All these mechanisms may operate simultaneously as taxane resistance is multi-factorial. Here, we review the cell biology understanding of nuclear envelope breaking in production of micronucleation, and nuclear membrane rupture and repair, and propose that these processes are involved in taxane resistance.

Factors Influencing Patients' Decisions to Use Health Services for Retreatment at Putri Hijau Medan TK II Hospital in 2023

Patient behavior as consumers in utilizing health services, including the decision to seek re-treatment, is influenced by several factors such as the quality of doctor/nurse services, distance, facilities, and speed of service. This study aims to analyze the factors that influence patients' decisions to utilize health services for repeat treatment. The research method used was quantitative with a cross-sectional design, carried out at the Putri Hijau Level II Hospital in Medan. A sample of 247 people was selected using the accidental sampling method from a population of 3,946 people. Data analysis used univariate, bivariate chi-square, and multivariate approaches with multiple logistic regression at a 95% confidence level. The research results show that the quality of doctor/nurse services, distance, facilities, and speed of service have a significant influence on the patient's decision to seek treatment again. Meanwhile, factors such as age, gender, education, and employment do not have a significant effect. The most dominant factor is facilities, where respondents who feel that hospital facilities are good have a higher chance of undergoing repeat treatment. This research concludes that factors such as the quality of doctor/nurse services, distance, facilities, and speed of service have a significant influence on patients' decisions in utilizing health services for re-treatment at Putri Hijau Level II Hospital in Medan. It is recommended that the hospital allocate a budget to improve facilities that are still lacking and improve new service facilities to increase public confidence in seeking treatment again.

Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation.

To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. Multi-institutional historical cohort study. Five tertiary care referral centers. Adults ≥18 years old with sporadic VS. Primary and repeat treatment with SRS. Microsurgery-free survival after repeat SRS. Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

Safety and Efficacy of Cryotherapy for the Treatment of Renal Angiomyolipoma Related to Tuberous Sclerosis Complex: The Cryo-TSC Study

Purpose: Tuberous sclerosis complex (TSC) is a rare autosomal dominant inherited disease, in which approximately 60% to 80% of patients have bilateral angiomyolipoma (AML). There is a need for repeatable local treatments of TSC-AML. Cryotherapy is an option for renal tumors; however, its safety and efficacy for vascular tumors, such as TSC-AML, are unclear. The aim of this study was to establish the safety and efficacy of cryotherapy for TSC-AML. Materials and Methods: This was an open-label, single-arm, prospective phase II study to evaluate the safety and efficacy of cryotherapy for TSC-AML of ≤ 4 cm. Cryotherapy was performed using the CryoHit device with a percutaneous approach. Safety was assessed 1, 2, 6, and 9 months after cryotherapy, and efficacy was assessed 3 and 9 months after cryotherapy. The efficacy of cryotherapy was evaluated using the modified RECIST or RECIST criteria by independent central review. The primary end point was the disease control rate, and secondary end points were the overall response rate, safety, renal function, quality of life, and whether additional treatment was required. Results: The disease control rate was 100%, and the overall response rate was 93.3%. After 9 months of follow-up, the median estimated glomerular filtration rate decreased slightly (from 89.2 mL/min/1.73 m2 to 79.4 mL/min/1.73 m2). Quality of life was stable, and no additional treatment was needed. Three Grade 3 adverse events (hematuria, chronic kidney disease, and elevated aspartate aminotransferase) were observed in 3 patients, respectively, but no additional treatments were required. Conclusions: Cryotherapy for TSC-AML can be performed safely and efficiently. Cryotherapy can be a new therapeutic option for TSC-AML. Trial Registration Number: jRCTs072200039.

Update on GALLANT: A phase 2 study using metronomic gemcitabine, doxorubicin, and docetaxel plus nivolumab in previously treated sarcoma (NCT04535713).

e23569 Background: Metronomic dosing of gemcitabine, doxorubicin and docetaxel causes less severe side effects than standard chemotherapy for advanced sarcoma. Hypothesis: The addition of nivolumab to this regimen will have synergistic effects and improve treatment outcomes. Objectives: Primary objective: To assess progression-free survival (PFS); Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival (OS) rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Methods: Inclusion criteria: Previously treated male and female subjects, > 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if the toxicity grade is <1. Results: Efficacy (n = 70). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. Best Overall Response = 14 PR, 47 SD, 9 PD. ORR = 20%; DCR (CR+PR+SD) was 87%. Median PFS was 8.2 (95% CI: 5.85-10.55) months; 6- month PFS rate of 59%. Median OS was 17.6 (95% CI: 13.53-21.67) months, with 6-month OS of 84%. Safety (n = 75): Grade 3/4 TRAEs include thrombocytopenia (n = 26), white blood cell count decreased (n = 17), neutropenia (n = 16), fatigue (n = 15), anemia (n = 13), nausea (n = 9), anorexia (n = 5), diarrhea (n = 2), emesis (n = 1), febrile neutropenia (n = 1), sepsis (n = 1), rectal bleeding (n = 1), transaminitis (n = 1), dizziness (n = 1), shortness of breath (n = 1). There were no unexpected adverse events reported. Conclusions: Taken together, the data suggests that nivolumab plus metronomic doses of gemcitabine, doxorubicin and docetaxel (1) may have synergistic activity, and (2) by indirect comparison, may be as effective as standard first line therapy for advanced sarcoma with manageable toxicity. Clinical trial information: NCT04535713 .

Penerapan Terapi Murottal dan Bermain Terapeutik dalam Asuhan keperawatan pada Pasien Anak Leukemia Limfoblastik akut (ALL) dengan Ansietas di Ruangan Kronis Irna Anak RSUP Dr. M. Djamil Padang

Leukemia is the most common type of cancer in children. Long and repeated treatment periods cause children to experience hospitalization which has a psychological impact. One of the psychological impacts that children most often experience is anxiety. Anxiety needs to be anticipated, controlled and overcome so that the patient's quality of life remains optimal. One way is murottal therapy and therapeutic coloring play. Dr. Dr. Hospital's medical record data. M. Djamil Padang, recorded 169 cases of leukemia in 2022. The research aims to apply murottal therapy and therapeutic play (coloring) in the care of pediatric patients with Acute Lymphoblastic Leukemia (ALL) with anxiety in the chronic room of IRNA Children's Hospital Dr. M. Djamil Padang. Descriptive research design with a case study approach in the pediatric IRNA chronic room from 15 May - 3 June 2023. The research population was all 8 pediatric patients with ALL. The sample was 2 participants with ALL who met the criteria. The results of the research on the second participant showed a difference in anxiety levels before and after murottal therapy and therapeutic play (coloring) from anxiety level 5 (very anxious) to 2 (happy). Advice to nurses in the children's room to carry out Murottal therapy and therapeutic play for leukemia children who experience anxiety due to hospitalization.

Repeated Exposure of Vancomycin to Vancomycin-Susceptible Staphylococcus aureus(VSSA) Parent Emerged VISA and VRSA Strains with Enhanced Virulence Potentials.

The emergence of resistance against the last-resort antibiotic vancomycin in staphylococcal infections is a serious concern for human health. Although various drug-resistant pathogens of diverse genetic backgrounds show higher virulence potential, the underlying mechanism behind this is not yet clear due to variability in their genetic dispositions. In this study, we investigated the correlation between resistance and virulence in adaptively evolved isogenic strains. The vancomycin-susceptible Staphylococcus aureus USA300 was exposed to various concentrations of vancomycin repeatedly as a mimic of the clinical regimen to obtain mutation(s)-accrued-clonally-selected (MACS) strains. The phenotypic analyses followed by expression of the representative genes responsible for virulence and resistance of MACS strains were investigated. MACS strains obtained under 2 and 8µg/ml vancomycin, named Van2 and Van8, respectively; showed enhanced vancomycin minimal inhibitory concentrations (MIC) to 4 and 16µg/ml, respectively. The cell adhesion and invasion of MACS strains increased in proportion to their MICs. The correlation between resistance and virulence potential was partially explained by the differential expression of genes known to be involved in both virulence and resistance in MACS strains compared to parent S. aureus USA300. Repeated treatment of vancomycin against vancomycin-susceptible S. aureus (VSSA) leads to the emergence of vancomycin-resistant strains with variable levels of enhanced virulence potentials.

Cannabidiol improves non-motor symptoms, attenuates neuroinflammation, and favours hippocampal newborn neuronal maturation in a rat model of Parkinsonism.

To investigate the effects of cannabidiol (CBD) on emotional and cognitive symptoms in rats with intra-nigral 6-hydroxydopamine (6-OHDA) lesions. Adult male Wistar rats received bilateral intranigral 6-OHDA infusions and were tested in a battery of behavioural paradigms to evaluate non-motor symptoms. The brains were obtained to evaluate the effects of CBD on hippocampal neurogenesis. 6-OHDA-lesioned rats exhibited memory impairments and despair-like behaviour in the novelty-suppressed feeding test and forced swim test, respectively. The animals also exhibited dopaminergic neuronal loss in the substantia nigra pars compacta (SNpc), striatum, and ventral tegmental area and a reduction of hippocampal neurogenesis. CBD decreased dopaminergic neuronal loss in the SNpc, reduced the mortality rate and decreased neuroinflammation in 6-OHDA-lesioned rats. In parallel, CBD prevented memory impairments and attenuated despair-like behaviour that were induced by bilateral intranigral 6-OHDA lesions. Repeated treatment with CBD favoured the neuronal maturation of newborn neurons in the hippocampus in Parkinsonian rats. The present findings suggest a potential beneficial effect of CBD on non-motor symptoms induced by intra-nigral 6-OHDA infusion in rats.

Abstract PO4-13-01: A randomised trial comparing 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early breast cancer (REaCT-ZOL): Quality of life and toxicity outcomes

Abstract Background: While adjuvant 6-monthly zoledronate is widely used in patients with early-stage breast cancer (EBC), questions remain around optimal scheduling of adjuvant bisphosphonates. We reviewed quality of life and bisphosphonate-related toxicities observed within a prospective randomised trial. Methods: Patients with EBC were randomised to either a single infusion of adjuvant zoledronate (4mg IV) or to 6-monthly treatment for 3 years. Quality of life was measured using the EQ-5D-5L questionnaire (before and after each infusion and 6-monthly thereafter in the single infusion arm). Acute phase reaction (APRs) data was collected after each infusion and data on other bisphosphonate-related toxicities (hypocalcaemia, renal impairment, ONJ and atypical fractures) was collected 6-monthly for 3 years. Results: Between 21-Nov-2018 and 02-Apr-2020, 211 patients were randomized to either a single infusion (n=107) or 6-monthly (n=104) adjuvant zoledronate. While each zoledronate infusion was associated with a worsening QoL, the overall QoL was the same in the two study arms. APRs occurred in 75% of patients after receiving zoledronate. Other bisphosphonate-related toxicities were uncommon in either arm. Significantly more patients discontinued study treatment in the 6-monthly arm (30/104, 28.8%) compared with the single infusion arm (3/107, 2.8%) (p < 0.001). The most common reason for study discontinuation was the occurrence of APRs, pain and malaise. Disease-free and overall survival rates were not significantly different in the study arms. Discussion: A single infusion of adjuvant zoledronate may offer patients a more convenient and better tolerate regimen than repeat infusions. APRs remain an important toxicity with repeat infusions of zoledronate, leading to increased rates of treatment discontinuation. Larger, definitive, trials comparing a single infusion with repeat treatments are required. Citation Format: Igor Machado, Lucas Clemons, Carol Stober, Gregory Pond, Arif Awan, Henry Conter, Demetrios Simos, Sukhbinder Dhesy-Thind, Mihaela Mates, Vikaash Kumar, John Hilton, Lisa Vandermeer, Mark Clemons. A randomised trial comparing 6-monthly dosing of adjuvant zoledronate with a single one-time dose in patients with early breast cancer (REaCT-ZOL): Quality of life and toxicity outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-01.

Abstract PO1-21-01: A Case of High Grade Metastatic Encapsulated Papillary Carcinoma and a Look at Current Treatment Guidelines

Abstract Background: Encapsulated papillary carcinoma is a well-documented malignancy in the world of breast surgery. It is often described as a less invasive form of breast cancer, with a more indolent clinical course. Most EPC pathology demonstrates low grade tumors, with rare findings of metastases at time of diagnosis. EPC currently accounts for 1-2% of all breast cancers. It is distinguished by its fibrovascular core, which is covered with epithelium with or without a myoepithelial layer. Despite EPC being well-recognized, current management remains controversial. Most commonly, however, it is treated and managed as an in-situ disease. Case Presentation: We present a case of a 64-year-old female who initially presented with a painless lump in her left breast, which on biopsy demonstrated DCIS involved with a papillary lesion. On excision, the patient was upstaged to IDC in a background of EPC. She then underwent re-excision with confirmed negative margins. Despite this, over the following months, the patient continued to have increased pain, swelling, and an episode of superficial thrombophlebitis. She was taken back to the OR at this time and was found to have a new mass with a large feeding vein. Pathology was significant for high grade multifocal EPC with small and large vessel lympho-vascular invasion. Lesion noted to be metachronous. Additionally, metastases to the axilla were identified, requiring an axillary dissection. Conclusion: High grade encapsulated papillary carcinoma is a rare member of the indolent papillary breast cancer family. This unusually invasive type of cancer should be treated and managed in a more aggressive fashion, like its clinically similar cousin invasive ductal carcinoma. The current management standard of treating EPC as in situ disease is not robust enough and can lead to disease recurrence and need for repeat resection and treatment. Citation Format: Nicholas Gore MD, Madeline Silva MD, Carissia Calvo-Strube MD. A Case of High Grade Metastatic Encapsulated Papillary Carcinoma and a Look at Current Treatment Guidelines [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-21-01.

Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence.Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.

Resin infiltration for white spot lesions: An in vitro experimental trial.

To evaluate the aesthetic outcome by varying the duration allowed for infiltrant penetration when treating white spot lesions with resin infiltration. An in vitro, experimental randomised study. Artificially created white spot lesions (WSLs) were induced on 100 extracted anterior teeth (T1). Teeth were divided into enamel and dentine groups depending on the extent of the lesion and then randomly assigned into different treatment protocol groups: penetration times of 3, 6 and 9 min. Resin infiltration treatment was applied according to the treatment protocol assigned (T2). Samples were thermocycled for 10,000 cycles (1 clinical year) (T3). The samples from the 3-min enamel and dentine groups were then randomly assigned into either a repeat treatment or no additional treatment group (T4). Samples were then thermocycled for an additional 10,000 cycles (T5). Spectrophotometric analysis was measured colour change (ΔE) for all groups. Mean ΔE values equal to or greater than the critical value (3.7) indicate a detectable clinical difference in colour of the treated WSL when compared to before WSL formation. Mean ΔE values, for the enamel groups, were slightly above or significantly below the critical value, and for the dentine groups, were significantly above the critical value. Mean ΔE values within the enamel and dentine groups both demonstrated a downward trend with increasing time allowed for resin infiltrant penetration (P < 0.05). No significant mean ΔE difference (P = 0.53) was found between groups that received a single or repeat treatment. After the first thermocycling event, no significant difference in colour change was observed in all groups except for the deep dentine lesion treated for 3 min. There was a significant difference in colour change for all groups except the enamel group that received a single treatment following thermocycling after a single or repeat treatment. Increasing the resin infiltrant penetration time to at least 9 min is advised as the most optimised treatment protocol. Resin infiltration treatment should be done only once to treat a particular white spot lesion as subsequent treatment for the same lesion results in marginal colour improvement. The colour improvement of WSLs resulting from the resin infiltration treatment can be expected to last for at least 1 year. Resin infiltration treatment of shallow lesions with a single and optimised infiltration technique can be expected to last an additional year.

Patient Perceptions and Experiences With Maggot Debridement Therapy for Managing Chronic Wounds.

The purpose of this study was to describe patient experiences and satisfaction with use of maggot debridement therapy (MDT) for hard-to-heal wounds. Descriptive, cross-sectional study. The sample comprised 60 participants, 60% were male (n = 36). Their mean age was 62.9 (SD = 20) years. Almost half of participants had lower extremity wounds (n = 26; 43.3%), diabetic foot ulcers (n = 18; 30%), and pressure injuries (n = 9; 15%). Most received maggot therapy via biobags (n = 36; 60%). Participants completed a questionnaire designed for purposes of the study that queried demographic and pertinent clinical characteristics, current health status including current topical therapies, and duration of their chronic wound. Nine items queried emotional responses prior to MDT, the amount and method of the maggot therapy, discomfort experienced during therapy, and sources of information regarding this treatment. Emotional responses before starting MDT included disgust (n = 30, 50%), anxiety (n = 26, 43.3%), doubts about its effectiveness (n =20, 33.3%), and disbelief (n = 11, 18.3%). Approximately one-third of participants reported feelings of biting, itching, and fear of the maggots. Despite these feelings, a majority (n = 38, 63.3%) indicated that they were pleased with treatment outcome and willing to undergo additional MDT if needed. While a majority of participants with nonhealing chronic wounds reported negative emotions association with MDT, more than half indicated that they were pleased with the outcome of treatment and willing to undergo repeat treatment if indicated.