Treatment Phase Research Articles

Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni.

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.

Single German centre experience with patient journey and care-relevant needs in amyloidosis: The German AMY-NEEDS research and care program.

Amyloidosis is a rare multi-system disorder associated with frequently delayed diagnosis, enormous disease burden and psychosocial distress. Systematic assessment of needs was performed by a subtype-spanning questionnaire-based survey within the AMY-NEEDS research and care program. 118 patients with proven amyloidosis (62.7% ATTR, 22.0% AL, 15.3% other forms) were included in August 2020 until February 2021 (mean age 71.2 ±11.3 years; 30% women). The median diagnostic delay between onset of symptoms and diagnosis was 9.0 (range: 2.5; 33.0) months. Local health care providers (HCPs) play a central role on the way to diagnosis. Diagnosis itself typically requires a clinical but not necessarily a university setting. In the treatment phase, the focus moves to the amyloidosis centre as primary contact and coordinator, with general practitioners (GPs) acting predominantly as a contact point in crisis and link to additional services. About half of patients reported impaired quality of life and one third suffering from anxiety and depressed mood, respectively. The majority of patients talk about their concerns with close caregivers and local HCPs. Advance care planning is a relevant, yet insufficiently met need. The journey of patients with amyloidotic disease, their contact partners and needs at different stages were characterized in detail within the German health care system. An amyloidosis-specific care concept has to master the multitude of interfaces connecting the numerous treatment providers involved with the amyloidosis centre and GPs as key players. Telemedical approaches could be a promising and well-accepted option allowing optimal coordination and communication.

Synergistic neuromodulation therapy for persistent spinal pain: a proof-of-concept trial on the use of spinal cord and dorsal root ganglion stimulation.

Persistent Spinal Pain Syndrome type 2 (PSPS-T2) poses a significant clinical challenge, demanding innovative therapeutic interventions. The integration of Spinal Cord Stimulation (SCS) and Dorsal Root Ganglion Stimulation (DRG-S) is emerging as a potent synergistic strategy for comprehensive pain management. This single patient-blind proof of concept (POC) trial explores the efficacy and synergistic potential of combined SCS and DRG-S in a patient with refractory PSPS-T2. A 45-year-old male with intractable PSPS-T2 underwent a unique, methodically structured study, involving three treatment phases: Phase A with SCS alone, Phase B with DRG-S alone, and Phase C The patient, blinded to the treatment modalities, provided pain assessments using the Visual Analogue Scale (VAS) and Douleur Neuropathique 4 Questions (DN4) conducted by clinical investigators at each phase. Baseline pain scores were ten and nine, respectively. Distinct responses were noted across the phases. Phase A demonstrated moderate pain relief, while Phase B offered further pain intensity reduction. However, Phase C, combining both strategies, yielded the most significant improvement, remarkably enhancing the patient's quality of life and functional capacity. This POC trial underscores the synergistic potential of SCS and DRG-S in managing complex cases of PSPS-T2, suggesting a paradigm shift towards integrated neuromodulation strategies for enhanced pain control. The development of dual intent implantable pulse generators (IPGs) capable of offering combination therapy simultaneously might be effective for pain management in select cases. The significant pain reduction and functional improvement observed advocate for further research in dual neuromodulation therapies. IRB 20190536.

Neferine alleviates ovariectomy-induced osteoporosis by enhancing osteogenic differentiation of bone marrow mesenchymal stem cells via regulation of the p38MAPK pathway

ABSTRACT Objective Osteoporosis, a skeletal ailment marked by bone metabolism imbalance and disruption of bone microarchitecture, Neferine, a bisbenzylisoquinoline alkaloid with diverse pharmacological activities, has received limited attention in the context of osteoporosis treatment. Methods We employed a bilateral ovariectomy (OVX) rat model to induce osteoporosis and subsequently administered Neferine treatment for four weeks following successful model establishment. Throughout the modeling and treatment phases, we closely monitored rat body weights. We assessed alterations in bone tissue microstructure through micro-CT, HE staining, and safranin O-fast green staining. Levels of bone formation and resorption markers in serum were evaluated using ELISA assay. Western blot analysis was employed to determine the expression levels of p38MAPK, p-p38MAPK, and bone formation-related genes in bone tissue. We isolated and cultured OVX rat BMSCs (OVX-BMSCs) and induced osteogenic differentiation while simultaneously introducing Neferine and the p38MAPK inhibitor SB203580 for intervention. Results Neferine treatment effectively curbed the rapid weight gain in OVX rats, ameliorated bone loss, and decreased serum levels of TRAP, CTX-I, PINP, and BALP. Most notably, Neferine promoted the expression of bone formation-related factors in bone tissue of OVX rats, while concurrently activating the p38MAPK signaling pathway. In in vitro experiments, Neferine facilitated the expression of bone formation-related factors in OVX-BMSCs, increased the osteogenic differentiation potential of OVX-BMSCs, and activated the p38MAPK signaling pathway. Nevertheless, SB203580 partially reversed Neferine’s promotive effect. Conclusion Neferine can boost the osteoblastic differentiation of BMSCs and alleviate OVX-induced osteoporosis in rats by activating the p38MAPK signaling pathway.

Comprehensive Virtual Treatment for Severe Anxiety in Youth: A Case Report

Anxiety disorders and obsessive-compulsive disorder (OCD) are among the most common mental health conditions in children and adolescents and are associated with various impairments and long-term consequences. Evidence-based treatments exist but are often lacking in elements needed to effectively treat youth with more severe presentations. This case report illustrates a patient’s treatment course in an innovative program for children, adolescents, and young adults with severe anxiety. The program offers a continuum of outpatient, evidence-based care tailored to the severity of the patient’s condition. The case study focuses on “Jane,” an adolescent female with anxiety as well as obsessive-compulsive spectrum disorders, who had previously received extensive treatment without sustained improvement. Through the program’s three treatment phases, Jane and her parents demonstrated consistent engagement and adherence to treatment. Jane showed significant progress, with rapid reduction in symptoms and functional impairment. This case report underscores key elements of this treatment that address gaps in traditional approaches to care, particularly for patients with severe presentations, including the coordinated, team-based approach; the continuum of evidence-based, phased treatment titrated to need; the utilization of virtual individual, group and parent-focused care and between-session coaching to enhance learning generalization; and the use of measurement-based care. Further research is warranted to evaluate the generalizability and long-term outcomes of this program and its potential to transform the treatment landscape for pediatric anxiety and OCD.

ENDOCARDITIS TEAM? DESIGNING AN ORIGINAL AND TAILORED CLINICAL PATHWAY

Abstract Infective endocarditis (IE) remains a poorly understood disease that primarily affects either native or prosthetic heart valves. Its incidence has increased over the past two decades, now affecting 3 to 10 individuals per 100.000/year in the general population. Despite advances in early diagnosis and surgical intervention, IE continues to pose a significant challenge, often leading to severe complications and carrying a substantial burden of morbidity and mortality. Data from the EURO–Endo registry show a drastic change in IE and provide an accurate picture of IE disease today. In European countries, it tends to affect older patients with a remarkable 12% of cases occurring in those aged ≥ 80 years. The traditional care pathway is often fragmented into multiple and potentially dangerous steps, resulting in delayed diagnosis and treatment. Such a “patchy” approach may cause suboptimal patient management, especially in the subset of frail patients with important concomitant diseases and high surgical risk. Clinical pathways (CPs) are an evidence–based multidisciplinary care plans involving diagnosis, treatment and rehabilitation phases, through which to follow patients from hospital admission to discharge, in order to manage a specific health condition, aiming to optimize patient and hospital/team outcomes, while contributing to a better organized care processes. In 2018, a working group composed by healthcare managers, infectious disease specialists, cardiac surgeons, cardiologists, anesthesiologists, geriatricians and other professionals involved in the care of IE patients have engineered a dedicated CP for IE at our institution. The CP introduced significant changes in the management of patients with IE. As a result, the quality of care and services offered increased, a faster and more appropriate diagnosis and treatment were achieved, patient outcomes and safety improved and a better coordination and continuity of care between different settings was guaranteed. The growing burden of IE in western countries demands an evidence–based multidisciplinary care plan. The creation of a territorial network ensures continuity and appropriateness of care in conjunction with the referring physicians/hospital and rationalization of resources. Although some controversies still exist, we believe that CP will have a positive impact on quality in health care.

Combination Treatment With Varenicline and Nicotine Patch on Smoking Cessation Outcomes in Heavy Drinkers at 26-Week Follow-up.

People who smoke cigarettes and drink alcohol heavily are less likely to quit smoking compared with those who do not drink heavily. The current study examined the effects of a 12-week treatment phase of combination varenicline and nicotine patch compared with placebo and nicotine patch on smoking cessation (primary outcome) and alcohol consumption (secondary outcome) in heavy drinking smokers at 26-week follow-up. Participants were daily smokers who met heavy drinking criteria. They were randomly assigned to receive either varenicline and nicotine patch (n = 61) or placebo and nicotine patch (n = 61) for 12 weeks. At week 26, self-reports of point prevalence cigarette abstinence were biochemically confirmed, and past-month alcohol drinking days and heavy drinking days were assessed. At week 26, smoking quit rates did not differ by treatment group (25% varenicline and 26% placebo). Relative to week 12 outcomes, week 26 quit rates significantly dropped off in the varenicline group but not in the placebo group. Alcohol drinking reductions for the whole sample that were previously observed from baseline to week 12 were sustained at week 26, although they did not differ between treatment groups. In heavy drinking smokers, smoking cessation success was evident in a quarter of the total sample at 3 months postmedication discontinuation. At this time, quit rates were the same between those who received varenicline and nicotine patch and those who received nicotine patch alone. Future research is warranted to examine what may aid in longer-term smoking quit rates in heavy drinking smokers.

Efficacy of EMDR in Body Dysmorphic Disorder and Associated Cognitive-Emotional Features

Body dysmorphic disorder (BDD) is a severe psychological disorder that significantly impacts functioning and quality of life. Eeye movement desensitization and reprocessing (EMDR) presents as an emerging alternate psychological intervention. This study aimed to examine the efficacy of EMDR in BDD symptoms and associated cognitive-emotional features. These features include appearance-based rejection sensitivity, body shame, and self-compassion. Our study utilized a multiple-baseline across-subjects design, monitoring four randomly allocated female patients with BDD over a 10-session/90-minute EMDR treatment phase and two follow-up sessions at 1 and 3 months, respectively. Our results showed that EMDR significantly reduced BDD symptoms (recovery percentage [RP] = 60.54), appearance-based rejection sensitivity (RP = 36.56), and body shame (RP = 54.82) and increased self-compassion (RP = 51.79). Therefore, our study suggests that EMDR may be an effective treatment for BDD patients.

Treatment of localized rectal cancer in 2024

The management of localized rectal cancer has evolved significantly over the last two years. On one hand, intensification of treatments (radio-chemotherapy, chemotherapy, then surgery) for the most advanced tumors has shown an improvement in clinical results compared to less intense regiments. On the other hand, the possibility, as for prostate cancers, of opting for active surveillance without surgery in patients presenting a complete clinical response after a treatment phase, is now accepted. More recently, the Swiss recommendations for the surveillance of rectal cancer have been modified and now differ from those of colon cancers, by incorporating pelvic MRI and rectoscopy in addition, as well as special guidelines for tumors under active surveillance.

Antidyslipidemic effect of ethanol extract of <i>Irvingia wombolu</i> seeds in high fat diet induced dyslipidemic rat

The antidyslipidemic activity of Irvingia wombolu ethanol seeds extract was studied in high fat diet induced dyslipidemic rats.Forty five (45) Wstar rats were grouped into 5 groups of 9 rats each. The animals were allowed 7 days acclimatization period. Group 1 was the control group and it received normal rat chow and water throughout the study. Groups 2 to 5 were given high fat diet for 14 days after which they were given normal rat chow till the end of the study. At the end of the 14 days, group 2 was not treated while group 3-5 were treated with 250, 500 and 1000mg/kg b.w ethanol extract of Irvingia wombolu seeds respectively for 28 days. The lipid profile of animals was evaluated three times: first after 14 days induction period (phase 1) i.e day 0 of treatment, second was taken 14 days after treatment (phase 2), third was taken 28 days after treatment (phase 3). The study lasted for 49 days and dimethyl sulphoxide was used as a vehicle for the extract. In phase 1, all the groups fed with high fat diet showed an increase in low density lipoprotein (LDL) triglyceride, total cholesterol and a decrease in high density lipoprotein (HDL) levels. In phase 2 there was a decrease in LDL, triglyceride and total cholesterol level in addition to increase in HDL for animals in all the treatment groups. It was observed that in phase 3 only 250mg/kg group showed a progressive decrease in LDL, triglyceride, total cholesterol and an increase in HDL levels while 500 and 1000 mg/kg b.w showed an increase in LDL, triglyceride and total cholesterol level and a decrease in HDL. The result of the present study demonstrated the antidyslipidemic effect of ethanol extract of Irvingia wombolu seeds at lower dose.

Evaluating the Nephroprotective and Hepato-protective Effects of Hypoestes rosea in Acetaminophen-Induced Toxicity in Albino Rats

The leaves of Hypoestes rosea are in use as traditional medicine in the Niger Delta areas in Nigeria and the Western part of Cameroun for the management of different ailments in children, such as anaemia, malaria, fever and other ailments. Regardless of its uses, scanty studies evaluating its organ protective effects exist. Therefore, this research study evaluates the nephroprotective and hepato-protective effects of Hypoestes rosea in acetaminophen-induced toxicity in Albino rats. The objectives of this research study are to evaluate the protective effect of Hypoestes rosea on the kidney and the liver of albino rats. Acetaminophen, which is frequently used as an analgesic and antipyretic drug at high doses, can be harmful to vital organs of the body, affecting the liver and kidneys. In this study, effects of an aqueous extract of Hypoestes rosea (AEHr) on liver function parameters and kidney function parameters of acetaminophen induced-toxicity in albino rats were evaluated using acute (15 days) and sub-chronic (30 days) duration of study and study group comprising of prophylactic (pre-treatment) and therapeutic (post-treatment) phases with six experimental groups in each phase. A total of 112 adult apparently healthy Albino rats weighing (180-220g) were used for this study, divided into six experimental groups of extract control (EC), negative control (NC), positive control (PC), AEHr100mg/kg b w., AEHr 200mg/kg b w., and AEHr 300mg/kg b w. groups each of six rats. At the end of the research study period, blood samples were collected through jugular puncture for liver and kidney function parameters. Results showed that acetaminophen-induced toxicity in albino rats caused toxicity to the kidney and toxicity to the liver, as evidenced by the raised levels of potassium, urea, creatinine and low bicarbonate from the renal function parameters and also as evidenced by significant elevation of bilirubin and liver enzymes with a significantly low total protein and albumin levels from the liver function parameters when compared with other experimental groups. Conversely, AEHr at different concentrations in a dose-dependent pattern at the different treatment phases and different duration periods were able to repair the injury to the kidney and liver caused by acetaminophen induction to normal. Consequently, the findings of this research propose that Hypoestes rosea contains active ingredients accountable for the nephroprotective and hepato-protective abilities in rats and can be recommended for more studies using higher mammals.

Proportion of inflammatory bowel diseases patients withsuboptimal disease control in daily clinical practice-Real-world evidence from the inflammatory bowel diseases-podcast study.

Crohn's disease and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by a progressive nature of the disease resulting in subsequent intestinal damage, limited efficacy of current treatments and suboptimal disease management and a significant burden for patients. The IBD-PODCAST study aims to estimate the proportion of Crohn's disease and UC patients with suboptimal disease control (SDC) in a real-world setting. A non-interventional and cross-sectional study was conducted across 103 sites in 10 countries (Austria, Belgium, Canada, Germany, Greece, Italy, Portugal, Spain, Turkey, and UK). Criteria for SDC were based on STRIDE-II criteria and adapted by an expert panel. 2185 patients (Crohn's disease: n=1,108, UC: n=1077) with a mean (SD) age of 44.0 (14.8) years and mean (SD) disease duration of 12.4 (9.2) years were included (52.2% male). Ileal involvement was present in 39.1% of Crohn's disease patients, 35.3% of UC patients had extensive colitis. 77.3% of Crohn's disease and 65.3% of UC patients were on targeted immunomodulators and, according to STRIDE-II-based treatment phases, 85.6% of Crohn's disease and 85.4% of UC patients were assigned to the long-term treatment phase. SDC was detected in 52.2% of Crohn's disease and 44.3% of UC patients predominantly due to impaired quality of life (QoL), clinically significant extraintestinal manifestations, steroid overuse, signs of active inflammation in UC and Crohn's disease, and active fistulas in Crohn's disease. More than one criterion was seen in 37% of patients with SDC. Opportunities for on-label treatment optimization were observed in 49% of Crohn's disease and 61% of UC patients on advanced therapy. The high percentage of SDC in this global, real-world cohort suggests a large disease burden and high unmet medical need in IBD patients. Future analysis should focus on monitoring and responding to SDC in this cohort and on patients' QoL.

Efficient Removal of Water Soluble Fraction of Diesel Oil by Biochar Sorption Supported by Microbiological Degradation

The contamination of the water bodies by diesel oil (DO) and its water-soluble fraction (WSF) represents one of the most challenging tasks in the management of polluted water streams. This paper contains data related to the synthesis and characteristics of the plum stone biochar material (PmS-B), which was made from waste plum stones (PmS), along with its possible application in the sorption of the WSF of DO from contaminated water. Techniques applied in sample characterisation and comparisons were: Elemental Organic Analysis (EOA), Scanning Electron Microscopy−Energy Dispersive X-ray Spectroscopy (SEM-EDX), Fourier Transform Infrared Spectroscopy (FTIR), pH (pHsus) and point of zero charge (pHpzc). In order to increase the overall efficiency of the removal process, sorption and bioremediation were subsequently combined. Firstly, PmS-B was used as a sorbent of WSF, and then the remaining solution was additionally treated with a specific consortium of microorganisms. After the first treatment phase, the initial concentration of diesel WSF was reduced by more than 90%, where most of the aromatic components of DO were removed by sorption. The sorption equilibrium results were best fitted by the Sips isotherm model, where the maximum sorption capacity was found to be 40.72 mg/g. The rest of the hydrocarbon components that remained in the solution were further subjected to the biodegradation process by a consortium of microorganisms. Microbial degradation lasted 19 days and reduced the total diesel WSF concentration to 0.46 mg/L. In order to confirm the non-toxicity of the water sample after this two-stage treatment, eco-toxicity tests based on a microbial biosensor (Aliivibrio fischeri) were applied, confirming the high efficiency of the proposed method.

The application of neuronavigated rTMS of the supplementary motor area and rhythmic speech training for stuttering intervention.

Stuttering, a neurodevelopmental speech fluency disorder, is associated with intermittent disruptions of speech-motor control. Behavioural treatments for adults who stutter (AWS) concentrate on adopting speech patterns that enhance fluency, such as speaking rhythmically or prolonging speech sounds. However, maintaining these treatment benefits can be challenging. Neuroimaging studies suggest that supplementary motor area (SMA) which play a crucial role in speech initiation, planning and internal timing shows aberrant activation in speech production of AWS and may contribute to stuttering. Preliminary evidence suggests that brain stimulation may impact responsiveness to behavioural treatments. The present study aims to investigate whether excitatory repetitive transcranial magnetic stimulation (rTMS) of the SMA and rhythmic speech can consistently reduce stuttering severity across various measures. Ten self-identified Cantonese-speaking AWS participated in this double-blinded, sham-controlled clinical trial study (NCT05472181). The participants underwent 10 sessions of rhythmic speech training across two phases, combined with either neuronavigated rTMS or sham, with a 2-week washout period between phases. The stuttering severity was assessed through various outcome measures, including the percentage of syllables stuttered, self-perceived stuttering severity, and the brief version of Unhelpful Thoughts and Beliefs About Stuttering before and after each treatment phase. Results demonstrated improved speech fluency in various speaking contexts, with no significant difference between rTMS and sham conditions immediately and 1 week post-treatment. Notably, rTMS specifically led to less stuttering in tongue twister production (d = -0.70). Both treatment conditions effectively reduced self-perceived stuttering severity and negative thoughts and beliefs about stuttering. The findings of this study indicate that stimulating the SMA reduced stuttering, only in the production of tongue twisters that may require greater motor control and coordination. Furthermore, it indicates that rhythmic speech might help alleviate negative beliefs and anxiety related to stuttering. This research contributes to our understanding of neuromodulation in stuttering treatment and the role of the SMA in speech motor control and emphasises the need for more research on the potential benefits and limitations of applying rTMS in this condition. What is already known on the subject Behavioural treatments for adults who stutter concentrate on adopting speech patterns that enhance fluency, such as speaking rhythmically or prolonging speech sounds. However, maintaining these treatment benefits can be challenging. Neuroimaging studies indicate that aberrant neural activation in speech production regions, like the supplementary motor area (SMA), is involved in stuttering. The SMA plays a crucial role in initiating, planning, and sequencing motor behaviours. Preliminary evidence suggests that brain stimulation (e.g., transcranial direct current stimulation or transcranial magnetic stimulation) may impact responsiveness to behavioural treatments. What this paper adds to existing knowledge There is limited knowledge regarding the potential effects of stimulating the SMA to enhance speech fluency in people who stutter. Existing research primarily consists of single case studies that lack proper control conditions or involve only a single stimulation session. Due to their limited scope and power, these studies may not provide sufficient evidence. The current study expands upon existing research by investigating whether multiple sessions of repetitive transcranial magnetic stimulation over the SMA, combined with rhythmic speech, improve speech fluency in adults who stutter. Furthermore, it addresses the limitations of brain stimulation methods and proposes directions for future research. What are the potential or actual clinical implications of this work? This study implies that the stimulation of SMA reduced stuttering only in speaking contexts that may require greater motor control and coordination such as tongue twisters. Additionally, the research suggests that using rhythmic speech could potentially alleviate negative beliefs and anxiety associated with stuttering.

Evaluation of the offset couch parameter between kilovoltage on-board imaging and cone-beam computed tomography in patients with prostate cancer

Background: External Beam Radiation Therapy (EBRT) is a curative therapy technique for prostate cancer. Since the prostate is unstable and surrounded by the bladder and rectum, precision of the target location is critical. Image Guided Radiation Therapy (IGRT) can improve treatment precision. The bladder and rectum may alter volume during IGRT, shifting the prostate’s position and resulting in missed target volume doses and extra organs at risk (OARs) doses. Objective: To assess setup error and residual error during patient positioning, as well as the current IGRT protocol efficiency, in prostate cancer patients while recommending a planning target volume (PTV) margin. Materials and methods: The offset couch parameter of on-board imaging (OBI) and cone-beam computed tomography (CBCT) was computed to determine the error distribution, magnitude, and error difference between treatment phases. The systematic and random errors were calculated using the van Herk equation to determine the planning target volume (PTV) margin. Results: The setup error was -0.86 to 0.25 mm, and the residual error was -0.15 to 0.32 mm. The couch displacement percentage for OBI was 29.44% to 58.89%, and for CBCT was 8.10% to 34.12%. The systematic error was 1.65 to 3.21. The random error was 1.78 to 3.29. The setup error was greatest in the longitudinal (Lng) direction, residual error was greatest in the vertical (Vrt) direction, and systematic and random error were greatest in the Vrt and lateral (Lat) direction, respectively. The PTV margin was greatest in the Vrt direction, while the Lng direction was the narrowest margin for every treatment phase. Conclusion: The highest setup error occurs in the Lng direction for all treatment phases. For the 46 Gy and 60 Gy phases, the highest residual error is in the Vrt direction. However, in the 78 Gy phase, the error is relatively close to 0.01mm in every direction. The current IGRT protocol is effective in detecting setup and residual errors. The 78 Gy phase has the greatest PTV margin, whereas the 46 Gy phase shows the narrowest margins in all directions.

281 Effects of dietary Aspergillus oryzae postbiotic during gestation and lactation on sow and progeny performance

Abstract This study aimed to evaluate effects of Aspergillus oryzae postbiotic (AOP) supplementation in gestation and lactation diets on sow performance, litter performance, and offspring performance through the nursery period. Sows [n = 118; Landrace × Yorkshire; body weight (BW) = 238 ± 2.2 kg; parit y= 3.8 ± 0.32] were blocked by parity and assigned randomly to one of two treatments. Treatments were a control diet and a control diet supplemented with AOP (Biozyme Inc.) at 1.5 g/sow/d in gestation from 5 days before breeding until farrowing, and adjusted to 1.55 g•sow-1•d-1 during lactation. Sow BW and P2 backfat thickness were measured on d 0, 30, and 109 of gestation and 24 h postpartum and at weaning on d 20 ± 2. Litters were standardized to 13 piglets within 24 h of farrowing. Piglets were weighed individually at birth, after 24 h, and at weaning. At weaning, 369 pigs were allotted to pens within maternal dietary treatment (48 pens, with 7 or 8 pigs/pen) for a 42-d nursery trial. All pigs received a common nursery diet in 3 dietary phases. Sows fed AOP had a lighter (P < 0.01) BW than those in the control group on d 109 of gestation (234.1 vs 244.1 kg) and post-farrowing (227.4 vs 236.7 kg), respectively, but not at other time points. Moreover, sows fed AOP showed less (P < 0.01) BW loss from d 109 of gestation to weaning (-0.9 vs -7.8 kg) and from post-farrowing to weaning (4.1 vs -1.9 kg) compared with control sows. Total feed intake and average daily feed intake (Control: 6.0 vs AOP: 6.2 kg/d) during lactation were not impacted (P > 0.10) by dietary treatments. Supplementation of AOP did not influence (P > 0.10) litter size (14.8 vs 16.0), litter birth weight (17.4 vs 18.2 kg), percentage of low birth weight piglets (13 vs 12.5 %) or normal birth weight piglets (87.0 vs 87.5 %), stillbirths (1.2 vs 1.2/litter), or mummies (0.9 vs 0.5/litter) for Control and AOP sows, respectively. Across treatments, no differences (P > 0.10) were observed for litter weight gain (43.2 vs 40.4 kg), average piglet BW at weaning (5.1 vs 4.9 kg), or piglet mortality rate (12.4 vs 13.1 %) for Control and AOP sows, respectively. Piglets weaned from AOP sows tended (P = 0.07) to have an increased average daily feed intake (ADFI) during the first week after weaning compared with pigs weaned from Control sows (0.28 vs 0.26 kg), but AOP did not influence other performance parameters for the entire nursery period. There were no interactions between maternal dietary treatment and nursery phase (P > 0.10), suggesting consistent responses to maternal dietary treatments over time. In summary, feeding sows AOP reduced sow BW loss but had no impact on litter or nursery performance.

Treating taboo thoughts on a psychiatric intensive care unit: a four-phase mixed methods single case experimental design.

Well-designed evaluations of psychological interventions on psychiatric intensive care units (PICUs) are a rarity. To evaluate the effectiveness of cognitive behaviour therapy for intrusive taboo thoughts with a patient diagnosed with bipolar affective disorder admitted to a PICU due to significant ongoing risk of harm to self. This was a four-phase ABC plus community follow-up (D) mixed methods n=1 single case experimental design. Four idiographic measures were collected daily across four phases; the baseline (A) was during PICU admission, the first treatment phase (B) was behavioural on the PICU, the second treatment phase (C) was cognitive on an acute ward and the follow-up phase (D) was conducted in the community. Four nomothetic measures were taken on admission, on discharge from the PICU, discharge from the acute ward and then at 4-week follow-up. The participant was also interviewed at follow-up using the Change Interview. Compared with baseline, the behavioural and the cognitive interventions appeared effective in terms of improving calmness, optimism and rumination, but the effects on sociability were poor. There was evidence across idiographic and nomothetic outcomes of a relapse during the follow-up phase in the community. Eleven idiographic changes were reported in the interview and these tended to be unexpected, related to the therapy and personally important. Single case methods can be responsive to tracking the progress of patients moving through in-patient pathways and differing modules of evidence-based interventions. There is a real need to implement robust outcome methodologies on PICUs to better evaluate the psychological aspects of care in this context.

Abstract PO3-11-11: Reproductive concerns of Japanese young women with breast cancer: a longitudinal study

Abstract Background: Treatment-related infertility is one of the major concerns of young women with breast cancer. We explored the longitudinal change and factors associated with reproductive concerns of Japanese young women in a prospective cohort study. Method: Women under the age of forty with newly diagnosed, histologically confirmed, operable breast cancer were recruited to “Hope for YBC Project” (UMIN000034481). The participants were asked to respond to anonymous self-written questionnaire regarding reproductive concern, anxiety and depression, perception of motherhood and socio-economic status at baseline and 6M. Result: Among 215 participants who were enrolled in the study, the mean age of 143 participants who responded to both the questionnaire at baseline and 6M was 35.7 (range 25-39): 78 (54.5%) had a university degree or higher, 104 (72.7%) had a partner, 65 (45.5%) had more than one child, and 84 (58.8%) had a household income more than 5 million yen. 57 (39.9%) had desire for having a baby, 37 (25.9%) were unsure and 43 (33.6%) were not interested. Among 143, 33 (23%) attempted fertility preservation. Baseline score of Reproductive Concerns After Cancer scale (RCAC) had weak correlation with the total scores of Hospital Anxiety and Depression Scale (HADS) (r=.397, p< .001) and Decision Conflict Scale (DCS) (r=.365, p< .001), respectively. Perceived “sufficient explanation of the risk of recurrence” and “sufficient explanation of the necessity and benefit of pharmacotherapy” were significantly associated with reduced DCS score at baseline (p< 0.001). The desire for having a baby changed in 15 women (10.5%) at 6M. Although both DCS and HADS significantly lowered at 6M, there was no difference between RCAC score at baseline and at 6M. RCAC score at 6M had correlation with RCAC(r=.793, p< .001), DCS(r=.439, p< .001), and HADS (r=.401, p< .001) scores at baseline. RCAC score at 6M was also associated with younger age (r=.311), non-existence of partner (p=.001), non-existence of child (p=.014), desire for having a baby (p< .001) at baseline, attempt of fertility preservation (p=.025) and not receiving endocrine treatment (p=.047). Conclusion: Reproductive concerns of young women remained throughout the treatment, and concerns at later treatment phase were associated with decision conflict and anxiety at diagnosis. These results shows that young women, especially those who have higher risk of having reproductive concern, need psychological and decision support at diagnosis, including thorough explanation of risk of recurrence and benefit of systemic treatment from oncologists. Citation Format: Chie Watanabe, Hiroko Bando, Akemi Kataoka, Mai Okazaki, Tadahiko Shien, Eriko Tokunaga, Takashi Kuwayama, Chikako Shimizu. Reproductive concerns of Japanese young women with breast cancer: a longitudinal study [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 PO3-11-11.

Abstract PO1-20-02: MiRaDor: A proof-of-concept study of treatment efficacy by monitoring Minimal Residual Disease (MRD) using circulating tumor DNA (ctDNA) in hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer (EBC)

Abstract Background: Detection of MRD through ctDNA has been consistently associated with high risk of relapse. Longitudinal evaluation of ctDNA to monitor MRD is a minimally invasive tool that may predict disease recurrence and treatment response. MiRaDor aims to improve the clinical utility of ctDNA and understand its applicability in high-risk, HR+/HER2- EBC patients (pts). Trial Design: MiRaDor (NCT05708235) is a multicenter, open-label, non-comparative, phase II trial. Selection criteria include pts: a) with HR+/HER2- EBC at high risk of relapse, b) on adjuvant treatment with endocrine therapy (ET) for at least 2 years with 3 additional years of planned ET, c) no prior treatment with cyclin-dependent kinases 4/6 inhibitors or fulvestrant, and d) had surgery for their primary BC in the last 5 years. The trial has two phases, ctDNA surveillance (n=1260) and treatment (n=40-60). The surveillance phase will analyze ctDNA, with the FoundationOne® Tracker, every 3 months for the 1st year and every 6 months thereafter until ctDNA detection, end of the adjuvant ET, or completion of treatment phase accrual. Pts with positive ctDNA without radiological disease progression (PD) will be allocated to 1 of the treatment arms (n=10): A) standard ET; B) giredestrant; C) giredestrant + abemaciclib; or D) giredestrant + inavolisib (if PIK3CA mutation). Treatment will continue until evidence of PD, physician’s and/or patient’s decision, or until the end of study treatment (abemaciclib/inavolisib for up to 2 years, 5 years for ET). Tumor assessments will be periodically performed to rule out radiological PD. The primary objective is to evaluate the rate of pts with at least 90% decrease or clearance in ctDNA after 3 months of treatment. Key secondary objectives include the proportion of pts with 90% decrease in baseline ctDNA at 6, 9, and 12 months, 70%, and 50% decrease in ctDNA at 3, 6, 9, and 12 months, and treatment safety and tolerability. A cohort expansion up to 20 pts in 1 or 2 arms will occur if at 3 months a 90% ctDNA decrease is observed in at least 30% of pts and if, after 3 additional months, a 90% ctDNA decrease is maintained in at least 20% of pts. Citation Format: Antonio Llombart-Cussac, José Manuel Pérez-García, María Gion, Daniel Alcalá-López, Janet Fazal-Salom, Alexandros Lazaris, Mario Mancino, Eileen Shimizu, Susana Victorino, Rui Rui Zhang, Zuzana Machackova, Frauke Schimmoller, Matthew Wongchenko, Joseph Gligorov, Peter Schmid, Javier Cortés. MiRaDor: A proof-of-concept study of treatment efficacy by monitoring Minimal Residual Disease (MRD) using circulating tumor DNA (ctDNA) in hormone receptor-positive/HER2-negative (HR+/HER2-) early breast cancer (EBC) [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 PO1-20-02.

Abstract PO3-28-08: Triple Hormone Receptor Signatures as Novel Prognostic Markers in Breast Cancer

Abstract Background Tumor phenotype across various cancers, including breast cancer, is predominantly shaped by a synergy between genomic alterations and the cell-of-origin from which the tumor emerges. These elements collectively influence crucial aspects like tumor aggressiveness, treatment response, and patient prognosis. While existing research highlights that the cell-of-origin often leaves a lasting imprint on the molecular architecture of tumors, leveraging this information for actionable clinical insights has proven challenging. Specifically, in the realm of breast cancer, utilizing cellular ancestry signatures could be a key factor in tailoring effective therapeutic strategies and improving patient outcomes. Methods In this study, we developed a unique signature anchored in the expression levels of triple hormone receptors (THR)—namely androgen (AR), estrogen (ER), and vitamin D (VDR)—in normal breast cells. Building on this, we formulated two distinct mRNA markers, THR-50 and THR-70, aimed at categorizing breast tumors based on their THR expression profiles. These markers were rigorously validated across 65 independent breast cancer studies, involving a total of 6,679 patients, utilizing Kaplan-Meier survival curves, Cox proportional hazards models, and unsupervised clustering analyses. Results Our findings indicate that both THR-50 and THR-70 are robustly associated with overall survival and recurrence-free survival in breast cancer patients across all datasets evaluated. Importantly, these THR signatures demonstrate broad applicability across various breast cancer subtypes, grades, and treatment phases—unlike conventional prognostic markers that tend to be subtype-specific. Additionally, the THR signatures have revealed four unique patient clusters with divergent survival outcomes, three of which are ER-positive and one ER-negative. When augmented with an immune-based signature (i20), THR-70 identifies a specific ER-negative breast cancer subgroup with a highly favorable prognosis, comparable to ER-positive subtypes, as well as another ER-negative subgroup characterized by exceedingly poor survival outcomes. Conclusion The THR-based cellular ancestry signatures open a new avenue in understanding the intricacies of breast cancer biology. These signatures offer a robust and stable framework for developing other prognostic markers, thus providing an enhanced stratification of existing breast cancer categories as well as creating new classifications. Citation Format: Mohamed Omar, Chuck Harrell, Rulla Tamimi, Luigi Marchionni, Tan Ince. Triple Hormone Receptor Signatures as Novel Prognostic Markers in Breast Cancer [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 PO3-28-08.