Patient Tolerance Research Articles

Efficacy of linaclotide in combination with polyethylene glycol for bowel preparation in Chinese patients undergoing colonoscopy polypectomy: protocol for a randomised controlled trial

BackgroundAdequate bowel preparation is essential for successful colonoscopy and polypectomy procedures. However, a significant proportion of patients still exhibit suboptimal bowel preparation, ranging from 18% to 35%. The effectiveness of...

Preparation Regimens to Improve Capsule Endoscopy visualization and diagnostic yield (PrepRICE); a multicentric randomized trial

Current guidelines recommend bowel preparation before small-bowel capsule endoscopy (SBCE). However, the optimal protocol is yet to be defined. To determine the best timing for preparation in SBCE, we compared small-bowel visualization quality (SBVQ), diagnostic yield (DY), and patient-reported outcomes across four purgative regimens. In this prospective, randomized (1:1:1:1), multicentric study, patients with suspected small bowel bleeding were randomized into four arms: G1 (1L of polyethylene-glycol + ascorbic acid [Moviprep®] the night before SBCE), G2 (1L in the morning, up to 2 hours before SBCE), G3 (0.5L up to 2 hours before + 0.5L after the capsule reached the duodenum), and G4 (1L after reaching the duodenum). To assess DY, lesions were categorized as having high (P2) or low (P0 or P1) bleeding potential. Small-bowel visualization quality (SBVQ) was assessed using the Brotz score. Transit times (TT) were measured, and patient tolerability was scored from 0 to 5 with higher scores indicating better tolerability. A total of 387 patients were included; 59% female with a median age of 73 years (IQR 23). The exam completion rate was lower in G1 (90%, p<0.001). Small bowel TT was shorter for patients receiving purgative during SBCE (G3 and G4, p=0.001). SBVQ was better in patients receiving purgative after reaching the SB (p<0.001): median of 7 for G1, 8 for G2, and 9 for G3 and G4. The overall DY of patients receiving intra-procedure purgatives (G3 + G4) was superior (42.7 vs 31.3%, p=0.02); significant differences were found in the second and third terciles. Likewise, G3 and G4 had higher angioectasia detection (p=0.04). Patients' satisfaction was significantly superior for G4 (median 4 points, IQR 1). The group that received the bowel preparation the night before SBCE had poorer outcomes. Intra-procedure purgative regimens reduced SBTT, enhanced visualization, improved DY, and increased angioectasia detection. G4 was the best-tolerated regimen.

A New Methodology for Evaluating the Potential Impact of Residual Refractive Astigmatism in Pseudophakic Patients.

To validate a new methodology to evaluate the impact of astigmatism in pseudophakia using an astigmatic defocus curve. Hospital Oftalmológico de Brasilia, Brazil. Non-randomized cohort study. For every point of the defocus curve, from -2.00 to +3.00 with 0.50D intervals, visual acuity was assessed with optically induced astigmatism (0.50D, 1.00D and 1.50D at 90 and 180 degrees) in pseudophakic patients implanted with a refractive-enhanced intraocular lens. Twelve patients were analyzed. A statistically significant difference was found between the 90° (ATR) and 180°(WTR) axis with 1.50D astigmatism, providing better visual acuity in ATR astigmatism (p < 0.05). This new methodology is reproducible, useful and may predict residual astigmatism tolerance in pseudophakic patients, which may help with surgery planning and IOL decision-making.

In vitro treatment with liposome-encapsulated Mannose-1-phosphate restores N-glycosylation in PMM2-CDG patient-derived fibroblasts

SummaryPMM2-CDG is the most common congenital disorder of glycosylation (CDG). Patients with this disease often carry compound heterozygous mutations of the gene encoding the phosphomannomutase 2 (PMM2) enzyme. PMM2 converts mannose-6-phosphate (M6P) to mannose-1-phosphate (M1P), which is a critical upstream metabolite for proper protein N-glycosylation. Therapeutic options for PMM2-CDG patients are limited to management of the disease symptoms, as no drug is currently approved to treat this disease. GLM101 is a M1P-loaded liposomal formulation being developed as a candidate drug to treat PMM2-CDG. This report describes the effect of GLM101 treatment on protein N-glycosylation of PMM2-CDG patient-derived fibroblasts. This treatment normalized intracellular GDP-mannose, increased the relative glycoprotein mannosylation content and TNFα-induced ICAM-1 expression. Moreover, glycomics profiling revealed that GLM101 treatment of PMM2-CDG fibroblasts resulted in normalization of most high mannose glycans and partial correction of multiple complex and hybrid glycans. In vivo characterization of GLM101 revealed its favorable pharmacokinetics, liver-targeted biodistribution, and tolerability profile with achieved systemic concentrations significantly greater than its effective in vitro potency. Taken as a whole, the results described in this report support further exploration of GLM101's safety, tolerability, and efficacy in PMM2-CDG patients.

Selexipag in patients with pulmonary arterial hypertension associated with connective tissue disease (PAH-CTD): Real-world experience from EXPOSURE.

Selexipag is indicated for the treatment of pulmonary arterial hypertension (PAH), including PAH associated with connective tissue disease (CTD), and further insights into the management of selexipag-treated PAH-CTD patients in clinical settings are needed. These analyses of the ongoing, multicenter, prospective EXPOSURE (EUPAS19085) study describe characteristics, treatment patterns, tolerability, and outcomes of PAH-CTD patients initiating selexipag in Europe/Canada. All analyses were descriptive, with idiopathic PAH patients who typically display better prognosis included for context. Six hundred ninety-eight selexipag-treated patients had follow-up information; 178 (26%) had PAH-CTD.The median age was 68 years, patients were predominantly female (88%), and with WHO functional class III symptoms (63%); the median time since diagnosis was 1.7 years.There were 5% patients at low, 25% intermediate-low, 40% intermediate-high, and 30% high risk of 1-year mortality, according to the ESC/ERS 4-strata risk score. Most (80%) initiated selexipag as a triple oral therapy, and most of these (62%) remained on triple therapy 6 months post-baseline. Over a median (Q1-Q3) selexipag exposure period of 8.6 (2.5-17.2) months, 79 (44%) patients discontinued selexipag; 36 (20%) due to tolerability/adverse events. Sixty (34%) patients were hospitalized at least once; 120 hospitalizations occurred, with 49 (48%) deemed PAH-related. Survival at 1 year was 85%, and at 2 years was 71%; 29 (16%) patients died. These results describe the use of combination therapy with selexipag for patients with PAH-CTD. These findings suggest an opportunity to optimize the benefits of selexipag among patients with PAH-CTD by moving from escalating after years in response to clinical deteriorationto escalating sooner to prevent clinical deterioration.

Cross-Over Study Evaluating Photobiomodulation in Pain Control in the Lower Limb.

Introduction Photobiomodulation is an emerging treatment modality in dermatology, with increasing use in doctors' offices. Photobiomodulation is the use of various light sources in the red light (620-700 nm) and near-infrared (700-1440 nm) spectrums as a form of light therapy. Objective The objective of the present study was to evaluate the use of photobiomodulation to improve pain in patients who take analgesics daily for chronic non-arterial leg ulcers. Method A cohort trial was performed with 20 patients to evaluate the improvement in pain, patient tolerance to treatment, and evolution of chronic, difficult-to-heal leg ulcers treated with low-frequency laser. Data were entered into a MicrosoftExcel spreadsheet (Microsoft Corporation, Redmond, WA, US). Statistical analysis used the Stats Direct 3 program with significance being set at an alpha error of 5% (p-value <0.05). Results An improvement in pain immediately after the first session was experienced by 18/20 patients; these patients remained pain-free for at least four days. One patient had suffered much pain during the entire day; a biopsy with culture and antibiogram was performed with the pain improving after treating an infection with appropriate antibiotics. However, one other case reported no improvement in the pain. Conclusion Photobiomodulation is an optional adjuvant therapy to improve pain in the treatment of chronic, difficult-to-heal leg ulcers.

Development of a Web-Based Interactive Tool for Visualizing Breast Cancer Clinical Trial Tolerability Data.

Longitudinal patient tolerability data collected as part of randomized controlled trials are often summarized in a way that loses information and does not capture the treatment experience. To address this, we developed an interactive web application to empower clinicians and researchers to explore and visualize patient tolerability data. We used adverse event (AE) data (Common Terminology Criteria for Adverse Events) and patient-reported outcomes (PROs) from the NSABP-B35 phase III clinical trial, which compared anastrozole with tamoxifen for breast cancer-free survival, to demonstrate the tools. An interactive web application was developed using R and the Shiny web application framework that generates Sankey diagrams to visualize AEs and PROs using four tools: AE Explorer, PRO Explorer, Cohort Explorer, and Custom Explorer. To illustrate how users can use the interactive tool, examples for each of the four applications are presented using data from the NSABP-B35 phase III trial and the NSABP-B30 trial for the Custom Explorer. In the AE and PRO explorers, users can select AEs or PROs to visualize within specified time periods and compare across treatments. In the cohort explorer, users can select a subset of patients with a specific symptom, severity, and treatment received to visualize the trajectory over time within a specified time interval. With the custom explorer, users can upload and visualize structured longitudinal toxicity and tolerability data. We have created an interactive web application and tool for clinicians and researchers to explore and visualize clinical trial tolerability data. This adaptable tool can be extended for other clinical trial data visualization and incorporated into future patient-clinician interactions regarding treatment decisions.

NEW STRATEGIES IN COMBATING FUNGAL PATHOGENS

Background. The relevance of the research is driven by the emerging trend of increasing resistance to existing drugs for the treatment of fungal infections. Addressing this issue is only possible by developing new formulations of antifungal agents or improving existing ones; studying the mechanisms of interaction of drugs with fungal cell walls and their exopolysaccharide matrices; refining delivery methods of antifungal agents, such as DectiSomes, for maximum effectiveness and minimizing side effects; expanding understanding of the immune response mechanisms to fungal infections and developing vaccines for the prevention of these diseases. The research aims to improve methods of diagnosis, treatment, and prevention of fungal infections to enhance the quality of life for patients and reduce the overall impact of these diseases on public health. Aim: To evaluate new treatment strategies for fungal infections to increase the effectiveness of antifungal agents, reduce their toxicity, and slow down the development of resistance. Materials and Methods: The materials for this study included publications of results from contemporary scientific research on the topic. The methods used for conducting the research were: a systematic approach and analysis, literary and critical analysis. Results. Prove the prospects for developing new strategies and techniques for antifungal therapy. By analyzing the results of clinical studies, including the assessment of the effectiveness of various antifungal drugs, it is possible to determine which ones are most effective under certain conditions and for specific types of fungal infections. New methodologies based on the principle of delivering or acting directly on the target area allow reducing the overall burden on the body. Better penetration of drugs into the skin and tissues allows for better control of fungal infection and accelerated healing process. Evaluating side reactions and patient tolerance levels to different drugs helps select antifungal agents that are the safest and most comfortable to use. Conclusion. Fungal infections continue to be a serious public health problem, and the development of new treatment and prevention methods is extremely important. Overall, research in these areas can help develop new therapeutic strategies that are more effective and safer for treating fungal infections, which pose a threat to humanity.

Comparison of Mindfulness-Based Cognitive Therapy and Integrated Transdiagnostic Psychotherapy for Emotion Regulation and Distress Tolerance

Introduction: Cardiac disease significantly impacts global health, causing substantial disability and mortality. This study compared the effectiveness of mindfulness-based cognitive therapy (MBCT) and integrated transdiagnostic psychotherapy (ITP) on emotion regulation and distress tolerance in patients with type D personality, characterized by social inhibition and negative affectivity. Methods: A semi-experimental design randomly assigned 60 cardiac patients with type D personality from Simorgh Heart Clinic, Mashhad, Iran, in 2022, to MBCT group (n = 20), ITP group (n = 20) and control group (n = 20). The MBCT and ITP groups received respective interventions, while the control group received no intervention. Emotion regulation and distress tolerance were assessed using validated scales before and after the interventions. Results: MBCT demonstrated significantly greater improvement in both emotion regulation and distress tolerance compared to ITP and the control group. Conclusion: This study suggests that MBCT may be a more effective intervention than ITP in improving emotion regulation and distress tolerance in cardiac patients with type D personality. Mindfulness-based approaches could offer valuable tools for managing emotional challenges in this population.

Evaluation of the Effectiveness of Using a Fixed Combination of Dorzolamide 2.0 % and Timolol 0.5 % in Primary Open-­Angle Glaucoma

The purpose of the work was to evaluate the effectiveness of the drug Domizia Duo® (OTCPharm JSC), which is a fixed combination (dorzolamide 20 mg/ml and timolol 5 mg/ml) in the treatment of patients diagnosed with primary open­angle glaucoma. The multicenter study involved 156 patients (280 eyes) with primary open­angle glaucoma (POAG) (136 patients — 243 eyes), primary angle­closure glaucoma (PACG) (8 patients — 15 eyes), ocular hypertension (12 patients — 22 eyes). 37 doctors from 22 medical institutions took part in the study. Patients aged 55–75 years with first­time POAG stages I–III, PAOG, ocular hypertension, as well as with abnormal intraocular pressure, patients with pseudophakia, if the diagnosis of glaucoma was made before cataract extraction and at least 6 months before the study, were included. According to the study results, intraocular pressure decreased significantly in all groups of patients and at all stages of treatment: primary open­angle glaucoma, primary angle­closure glaucoma, ocular hypertension. In 136 patients (243 eyes) with POAG, a 28 % reduction in IOP was achieved at an initial level of 25 (22–28) mm Hg. In the group of patients with PCOG (8 patients, 15 eyes), a decrease in IOP by 19 % was shown with an initial intraocular pressure of 20.1 (19.1–23.0) mm Hg. The high effectiveness of the drug Domizia Duo® (OTCPharm JSC) was established at all stages of POAG, so at stage I of newly diagnosed POAG, the reduction in IOP was 35.5 % within a month after the start of therapy, at stage II of newly diagnosed POAG by 28 %, at stage III by 44.4 %, in the group of patients with ocular hypertension, the degree of reduction in intraocular pressure was 27 % at an initial level of 26 (23–27) mm Hg. The data obtained from the study prove the high effectiveness of the fixed combination (FC) Domizia Duo® (OTCPharm JSC) against the background of good tolerability in patients with primary open­angle glaucoma (POAG) at stages I–III. The drug was also highly effective not only when prescribed as monotherapy, but also when switching from another drug or adding Domizia Duo® to treatment.

Elevated Plasma Levels of Growth Arrest Specific 6 (Gas6) Protein in Severe Obesity: Implications for Adipose Tissue and Inflammation.

BACKGROUND Preliminary data suggest an adipogenic role for growth arrest-specific 6 (Gas6), a pleiotropic molecule involved in inflammation, proliferation, and hemostasis through its Tyro3, Axl, and MerTK (TAM) receptors. This study compares Gas6 expression in plasma and visceral and subcutaneous adipose tissue in 42 adults with obesity (body mass index ≥40 kg/m²) and 32 normal-weight controls to elucidate its role in obesity and related metabolic alterations. MATERIAL AND METHODS Using a case-control design, we measured Gas6 levels in plasma via a validated sandwich enzyme-linked immunosorbent assay and in adipose tissues through quantitative polymerase chain reactio with specific probes. Medians and correlations were analyzed using Mann-Whitney and Spearman tests. A general linear model assessed the impact of covariates on the Gas6-anthropometric relationship, with statistical significance determined by P values. RESULTS Plasma Gas6 levels were significantly higher in the obese group than in controls (P=0.0006). While Gas6 mRNA expression did not significantly differ in subcutaneous adipose tissue between groups, it was notably higher in visceral than subcutaneous adipose tissue in controls (P<0.05). A significant correlation was found between plasma Gas6 levels and body mass index (P=0.001). CONCLUSIONS Gas6 plasma levels are elevated in morbid obesity, particularly in visceral adipose tissue, and are linked to altered glucose tolerance in female patients. These findings highlight the role of Gas6 in obesity-related metabolic complications and suggest avenues for further research and potential therapies.

Evolution of standardization of therapeutic and diagnostic allergens produced in Russia

Allergen-specific immunotherapy is based on the development of induced tolerance in patients. Natural extracts are most often used as therapeutic allergens worldwide.The article presents new approaches to biological standardization of subcutaneous administered allergens. It is established that own standard allergens have specific allergenic activity, which was determined on sensitized patients-volunteers. The Russian Federation uses its own units — EAA (Units of Allergenic Activity). 100 000 EAA/mL corresponds to the size of wheal in prick test equal to 8 mm. The internal reference material (RM) of allergenic activity of pollen allergens ”Microgen“ have different specific activity depending on the type of allergen. The most common series have allergenic (specific) activity in the range of 150,000 — 200,000 EAA/mL.The control of the specific activity of allergen drugs is carried out in accordance with the current certified standard samples of the company’s standards. A method of competitive enzyme-linked immunosorbent assay using specific sera containing specific IgE antibodies is used for this purpose.In addition, the specific activity of allergen preparations is certified through three additional characteristics: total protein content (using the Bradford method), protein profile (through electrophoresis in a polyacrylamide gel with sodium dodecyl sulfate under reducing conditions), and authenticity through the presence of major specific components, which is determined by the Western blot method using sera containing IgE antibodies specific for the corresponding allergen.Currently, in the Russian Federation, the standardization of therapeutic and diagnostic allergens is conducted simultaneously according to two indicators: protein nitrogen content, expressed in Protein Nitrogen Units (PNU), and allergenic (specific) activity expressed in units of allergenic activity per milliliter (EAA/ml). While the PNU indicator partially reflects the allergenic properties of the drug, it does not fully capture these properties, making it necessary to remove PNU from the list of quality indicators for allergen medicines. This would require changes to regulatory documentation and instructions for allergens.When evaluating the allergenic activity of allergens, it is now recommended to focus on units of EAA. The consistency of the protein composition and presentation in the drug ensures increased safety and efficacy of therapy, as well as allows for comparison between drugs.

Minute ventilation sensor-driven rate response as a part of cardiac resynchronization therapy optimization in older patients.

Chronotropic incompetence (CI) is common among elderly cardiac resynchronization therapy pacemaker (CRT-P) patients on optimal medical therapy. This study aimed to evaluate the impact of optimized rate-adaptive pacing utilizing the minute ventilation (MV) sensor on exercise tolerance. In a prospective, multicenter study, older patients (median age 76years) with a guideline-based indication for CRT were evaluated following CRT-P implantation. If there was no documented CI, requiring clinically rate-responsive pacing, the device was programmed DDD at pre-discharge. At 1month, a 6-min walk test (6MWT) was conducted. If the maximum heart rate was < 100bpm or < 80% of the age-predicted maximum, the response was considered CI. Patients with CI were programmed with DDDR. At 3months post-implant, the 6MWT was repeated in the correct respective programming mode. In addition, heart rate score (HRSc, defined as the percentage of all sensed and paced atrial events in the single tallest 10bpm histogram bin) was assessed at 1 and 3months. CI was identified in 46/61 (75%) of patients without prior indication at enrollment. MV sensor-based DDDR mode increased heart rate in CI patients similarly to non-CI patients with intrinsically driven heart rates during 6MWT. Walking distance increased substantially with DDDR (349 ± 132m vs. 376 ± 128m at 1 and 3months, respectively, p < 0.05). Furthermore, DDDR reduced HRSc by 14% (absolute reduction, p < 0.001) in those with more severe CI, i.e., HRSc ≥ 70%. Exercise tolerance in older CRT-P patients can be further improved by the utilization of an MV sensor.

Enhanced diaphragm excursion and exercise tolerance in COPD patients through inspiratory muscle training after standardised pulmonary rehabilitation: randomised controlled trial

Enhanced diaphragm excursion and exercise tolerance in COPD patients through inspiratory muscle training after standardised pulmonary rehabilitation: randomised controlled trial

Research Progress of Antibody-conjugated Drugs in Non-small Cell Lung Cancer

Lung cancer is the most common malignant tumor and the second most common malignant tumor in terms of mortality in the world. Non-small cell lung cancer (NSCLC) is the most common pathological type of lung cancer. Currently, the first-line standard treatment for advanced NSCLC is immunotherapy and targeted therapy. Although these treatments prolong the survival of patients, acquired drug resistance is still inevitable. Antibody-drug conjugates (ADCs) are a new type of anti-tumor drug made by coupling cytotoxic payloads to specific monoclonal antibodies via linkers. Compared with chemotherapy drugs, ADCs have the advantages of accurate recognition, local release, and high patient tolerance. In recent years, they have shown good clinical benefits in the treatment of NSCLC. This article provides an overview of the mechanism of action of ADCs, clinical studies progress in advanced NSCLC, and existing problems and challenges. .

Clinical Effects of Venetoclax in the Treatment of Acute Myeloid Leukemia in the Elderly

Objective: To investigate the clinical efficacy of venetoclax in the treatment of elderly acute myeloid leukemia (AML). Methods: 50 cases of elderly AML patients receiving venetoclax for treatment in the hospital from January 2022 to January 2024 were selected, including 38 cases of patients whose primary treatment was not suitable for intensive chemotherapy and 12 cases of relapsed/refractory AML patients, to observe the therapeutic efficacy and safety of venetoclax. Results: Among the 38 patients whose primary treatment was not suitable for intensive chemotherapy, 5 cases were treated with venetoclax monotherapy, 33 cases were treated with venetoclax + azacitidine, and 25 patients (65.79%) achieved complete remission (CR) with incomplete hematologic recovery (CRi) after 28 days of treatment; 10 patients with relapsed/refractory AML were treated with venetoclax + azacitidine, and 2 patients were treated with venetoclax + azacitidine + chemotherapy, and 2 patients achieved optimal therapeutic response after 28 days of treatment and CR/CRi was achieved in 7 patients (58.33%). There were 47 (94.0%) patients with grade 3 or higher granulocytopenia, 46 (92.0%) patients with hemoglobin reduction, and 43 (86.0%) patients with thrombocytopenia, developed after 28 days of treatment. 11 patients developed infections after treatment and there was one case of tumor lysis syndrome. Conclusion: The response rate of venetoclax monotherapy and combination in elderly AML induction therapy is high, and the overall tolerability of elderly patients is good, so it can be popularized and applied.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders.

To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders (NMOSD). A total of 33 patients with NMOSD treated with inebilizumab (Group INB, n=15) or rituximab (Group RTX, n=18) in addition to high-dose glucocorticoids were included. Both groups underwent hormone shock therapy during the acute phase. Subsequently, Group INB received inebilizumab injections during the remission phase, while Group RTX received rituximab injections. A comparison of aquaporins 4 (AQP4) titer values, peripheral blood B lymphocyte counts, and visual function recovery was conducted before and 8wk after treatment. Additionally, adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes. Following inebilizumab treatment, there was a significantly improvement in the visual acuity of NMOSD patients (P<0.05), accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio (P<0.05). Moreover, inebilizumab treatment showed a partial effect in preventing optic nerve atrophy (P<0.05). However, there were no significant differences in other therapeutic effects compared to rituximab, which has previously demonstrated substantial therapeutic efficacy (P>0.05). Furthermore, inebilizumab exhibited higher safety levels than that of rituximab injections. The combination of inebilizumab and high-dose glucocorticoids proves to be effective. In comparison to rituximab injections, inebilizumab displays better tolerance and safety. Moreover, it demonstrates a partial effect in preventing optic nerve atrophy. Thus, it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

DIPG-67. RE-IRRADIATION PRACTICES AND OUTCOMES IN PATIENTS WITH DIPG/DMG: A REPORT FROM THE INTERNATIONAL DIPG REGISTRY

Abstract BACKGROUND Given that radiation therapy is the only treatment modality demonstrated to result in any clinical benefit for children with DIPG, re-irradiation therapy has been explored as a treatment option for progressive DIPG. Several studies suggest re-irradiation is feasible, and may lengthen survival for children with progressive DIPG. However, any re-irradiation benefits are unclear and no standard of care (dose, fractionation, volume, timing, clinical status) has been defined. The aims of this study are to evaluate re-radiation therapy practices for children with progressive DIPG/DMG and to define a historical cohort of children with DIPG/DMG who have received re-radiation (re-XRT) for progressive DIPG/DMG. METHODS Data was extracted from the International DIPG Registry, and analyzed with descriptive statistics. RESULTS Of 1214 patients in the iDIPG Registry, 113 receiving re-XRT. Patients were diagnosed between 2002-2022, with the majority of patients diagnosed over the last decade. Of those 113 patients with specified data, at re-irradiation, n=68 (60%) received photon and n= 4 (4%) were treated with proton radiation. The median dose at re-XRT was 25 Gy (20-30 IQR) in 10 fractions (10-14 IQR). Time between initial XRT and re-XRT was 41.5 weeks (29.5-54 weeks). OS from diagnosis was 18 months (range, 15-23 mo); OS from re-XRT was 6 months (range, 4-10 mo). CONCLUSIONS Re-radiation therapy for children with DIPG/DMG is becoming a more common practice and appears to have OS benefit, with post-progression OS of 6 mo comparing favorably to historical data of 2.3 mo. [Cooney T et al, Neuro Oncol 2017] Efforts are underway to define patient selection and tolerability. Data extraction from the SIOPE DIPG/DMG Registry is also ongoing; data from both registries will be collated and uniformly presented.

(101) SHOCKWAVE THERAPY FOR THE TREATMENT OF POSTPARTUM STRESS URINARY INCONTINENCE: A PILOT STUDY

Abstract Introduction Stress urinary incontinence (SUI) is estimated to affect approximately 15% of adult women. Low-intensity extracorporeal shock wave therapy (Li-ESWT) is a form of electrohydraulic acoustic shockwave that has been shown to be effective in animal models of SUI. The Urogold100® is a Li-ESWT device that is FDA-cleared for improving blood flow, connective tissue activation, and pain relief, and it has been shown in multiple studies to be effective for mild to moderate erectile dysfunction and chronic pelvic pain in both men and women. While Li-ESWT has been investigated for related urologic conditions, minimal research exists as to its potential effectiveness for SUI in women. Objective Our aim was to evaluate the effectiveness of Li-ESWT for women with postpartum stress urinary incontinence in a pilot study. Methods Email recruitment was carried out in a single sexual medicine practice. Four women underwent weekly treatments with Li-ESWT for 4-6 weeks. All patients were postpartum women between ages 43-55. Treatment specifics included 1000 shocks at 2.5 Hz (initial visit) and 3.0 Hz (subsequent visits) distributed over the perineum and urethral opening. Energy level was based on patient tolerance, beginning with 0.06 Mj/mm2 and increased up to 0.08 Mj/mm2 for subsequent visits. Evaluation measures included the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Bladder Diary, both administered prior to treatment initiation and after treatment completion. The ICIQ-SF allowed patients to self-assess their urine leakage over the past several weeks (amount and frequency) while the Bladder Diary required patients to record specific leakage incidences throughout a single day. Results Prior to treatment initiation, patients reported 1-3 small daily urine leaks via the NIDDK Bladder Diary. All patients either improved or remained the same in this assessment post-treatment; all patients reported 1 small daily leak after treatment completion. Results from the subjective ICIQ-SF varied: 1 patient reported worsening from 1 daily leak to 2-3 daily leaks, which she attributed to increased water intake. Two patients reported improvements (several daily leaks to 1 weekly leak; several daily leaks to 2-3 weekly leaks). One patient reported no change. Subjective reporting from patients indicated 3 of the 4 felt the treatment was improving their symptoms, and the fourth patient reported no changes. Conclusions Our pilot study indicates that 3 of 4 patients showed improvements in their objective Bladder Diary recordings with reduced frequency of urine leakage, and 2 of 4 patients noted improvements in their subjective ICIQ-SF reporting. 3 of 4 provided positive verbal feedback as well. Despite the limited sample size, the improvements seen in the objective leakage frequency recordings are encouraging findings that warrant future investigation in a larger cohort. Given the noninvasive nature, ease of use, and high patient tolerability of Li-ESWT, this treatment modality should be considered for investigation in a larger cohort with the goal of relieving symptoms of SUI. Disclosure No.

Harnessing Metal Nanoparticles: Revolutionizing Cancer Therapy Through Targeted Drug Delivery and Tumor Microenvironment Modulation

Cancer remains a significant global health burden, claiming countless lives annually and incurring substantial direct and indirect economic costs. Despite advancements in therapeutic modalities, conventional cancer treatments, including chemotherapy, radiotherapy and surgery, are often hampered by limitations such as insufficient efficacy, dose-dependent side effects, high costs and patient tolerability. This has spurred extensive research into novel therapeutic approaches for this life-threatening disease. Metal nanoparticles (MNPs) have emerged as promising tools in cancer therapy due to their unique physicochemical properties spanning the past two decades. Owing to their size similarity to biological molecules, MNPs possess the inherent ability to penetrate cellular barriers, making them ideal carriers for targeted drug delivery. These multifunctional nanoplatforms offer distinct advantages over conventional therapeutics by enabling targeted delivery of anticancer agents to specific tumor sites, thereby enhancing therapeutic efficacy and minimizing systemic side effects. Photodynamic therapy and sonodynamic therapy represent particularly promising strategies that leverage MNPs for cancer treatment. This review delves into the potential applications of MNPs in modulating the tumor microenvironment, paving the way for the exploration of this vast and rapidly evolving field of nanomedicine.