Standard Of Care For Patients Research Articles

PREVALENCE OF HAND OR WRIST-RELATED PAIN AND ITS FUNCTIONAL LIMITATION AMONG HEALTHCARE PRACTITIONERS

Background: Work-related hand and wrist injuries are among the most common occupational traumas, particularly affecting healthcare practitioners due to prolonged manual tasks and repetitive movements. These injuries significantly impact the practitioners' functional abilities and overall productivity. Addressing this issue is critical not only to enhance the health and well-being of healthcare workers but also to maintain high standards of patient care. This study aimed to evaluate the prevalence of hand and wrist pain and its associated functional limitations among healthcare practitioners. Objective: To assess the prevalence and impact of hand and wrist pain on functional limitations among healthcare practitioners in diverse healthcare settings. Methods: A cross-sectional study was conducted between March 2024 and July 2024, involving 70 healthcare practitioners aged 21 to 35 years from Madinah Teaching Hospital, Faisalabad International Hospital, Civil Hospital, Sahil Hospital, and Prime Care Hospital. Approval was obtained from the Ethical Institutional Review Board (Ref: TUF/IRB/329/24). Participants were selected using purposive sampling, including those with at least one year of clinical experience and a minimum of four working hours per day. Data were collected using validated tools: Pain Rated Wrist/Hand Evaluation (PRWHE), Numeric Pain Rating Scale (NPRS), and Michigan Hand Outcome Questionnaire (MHOQ). Exclusion criteria included unhealed fractures, arthritis, neurological disorders, neoplasms, diagnosed diabetes mellitus, smoking or drug abuse >2 years, and systemic conditions affecting musculoskeletal function. Results: The PRWHE, NPRS, and MHOQ showed mean values of 31.57 (SD 18.75), 3.64 (SD 1.75), and 66.25 (SD 12.29), respectively. Functional domains of MHOQ recorded percentages for Function (59.42%), Activities of Daily Living (70.06%), Work (58.28%), Pain (36.35%), Aesthetics/Appearance (83.75%), and Satisfaction (61.85%). Urologists demonstrated the highest pain levels (PRWHE: 41.64; NPRS: 4.57) and lowest functional outcomes (MHOQ: Function: 50.71%). Surgeons exhibited the highest overall hand functionality (MHOQ: 69.16%), while nurses and dentists reported significant limitations in pain and work-related capabilities. Conclusion: The study identified a considerable prevalence of hand and wrist pain and associated functional limitations among healthcare practitioners. These findings underscore the necessity of ergonomic interventions and workplace modifications to alleviate musculoskeletal strain and improve the well-being and productivity of healthcare workers.

Adjunct Therapies to Standard Care for IBS and IBD Patients: Digestive Symptoms Improvement and Quality of Life Optimization.

Background: The prevalence of both inflammatory bowel diseases (IBD) and Irritable Bowel Syndrome (IBS) is increasing, with persistent digestive symptoms, an altered quality of life, and higher rates of anxiety, chronic fatigue, and sleep trouble than the general population. Methods: This scoping review will analyze the latest clinical practice recommendations and clinical studies on non-pharmaceutical interventions such as diet adaptations, physical activity, cognitive behavioral therapies, and medical nutrition therapies such as probiotics, soluble fibers, chitin-glucan, and micronutrients for digestive symptoms relief, quality of life improvement and nutritional deficiencies correction in IBS and IBD patients. The objective is to help healthcare practitioners and dietitians to build personalized care program for IBD and IBS patients. Results: Mediterranean diet, physical activity, cognitive behavioral therapies and medical nutrition therapies such as selected probiotics, soluble fibers, chitin glucan, peppermint oil and micronutrients are effective as adjunct therapies. Conclusions: These adjunct therapies may help to reduce persistent digestive symptoms, correct nutritional deficiencies and improve quality of life of IBS and IBD patients.

Explainable machine learning versus known nomogram for predicting non-sentinel lymph node metastases in breast cancer patients: A comparative study

IntroductionAxillary lymph node dissection (ALND) is the standard of care for breast cancer patients with positive sentinel lymph nodes (SLN), which are the first lymph nodes that drain the breast. However, many patients with positive SLNs may not have additional positive nodes, making the prediction of non-sentinel lymph node (NSLN) metastasis challenging. Reliable prognostic tools are essential for accurately assessing NSLN metastasis. The Memorial Sloan Kettering Cancer Center (MSKCC) nomogram has demonstrated effectiveness in this context, but it requires further evaluation within the Iranian breast cancer population. While ALND remains the gold standard, its unnecessary application in patients without evidence of additional positive nodes raises concerns due to potential complications such as lymphedema, nerve injury, and shoulder joint dysfunction. Furthermore, integrating Artificial Intelligence (AI) and Machine Learning (ML) techniques presents an opportunity to enhance the precision of NSLN metastasis predictions. MethodThis study conducts an extensive comparative analysis between the MSKCC nomogram and various ML models to predict NSLN metastasis, utilizing a dataset of Iranian breast cancer patients. Employing eXplainable Artificial Intelligence (XAI) methodologies, we analyzed 16 clinical features across a cohort of 183 patients. Our methodology includes rigorous statistical evaluations and the training and validation of ML models to assess the precision and robustness of these models compared to the MSKCC nomogram. ResultsOur analysis revealed that the Random Forest (RF) model outperformed the MSKCC nomogram, achieving an accuracy of 72.2 % and an AUC of 0.77, compared to the nomogram's AUC of 0.73. Logistic Regression (LR) also demonstrated competitive performance with an accuracy of 65 % and an AUC of 0.73. The RF model exhibited high sensitivity (75 %) and precision (73 %), effectively identifying critical predictors of NSLN metastasis, including the presence of ductal carcinoma in situ (DCIS) and tumor characteristics such as type and grade. Explainable AI techniques, particularly SHAP values, provided insights into feature importance, enhancing model interpretability. ConclusionOur study offers a comprehensive comparison between ML models and the MSKCC nomogram for predicting NSLN metastasis among Iranian breast cancer patients. These findings contribute valuable insights to the discourse on personalized treatment approaches, emphasizing the need for tailored prognostic tools across diverse populations. The implications of this research extend to clinical decision-making, potentially improving the accuracy and efficacy of breast cancer management within the Iranian healthcare landscape.

Adjuvant chemoradiotherapy plus PD-1 inhibitor for pN3 gastric cancer: a randomized, multicenter, Phase III trial.

D2 surgery followed by adjuvant chemotherapy has been established as the standard of care for patients with locally advanced gastric cancer in Asian countries. However, its efficacy is still unsatisfactory, especially for pathological N3 disease. The RACING trial is a randomized, multicenter, Phase III trial designed to compare the efficacy and safety of chemotherapy alone versus chemotherapy in combination with PD-1 inhibitor and radiotherapy in patients with pN3 gastric or gastroesophageal junction adenocarcinoma. A total of 433 patients will be assigned at a 1:1 ratio to the two arms. The primary end point is the 3-year disease-free survival rate. The secondary end points include the 3-year overall survival rate, 3-year local recurrence-free survival rate, treatment-related adverse events and quality of life.Clinical Trial Registration: NCT04997837 (ClinicalTrials.gov).

Real-World Outcomes of Selective RET Inhibitor Selpercatinib in the United States: Descriptive, Retrospective Findings from Two Databases.

This study described real-world patient characteristics and outcomes among selpercatinib-treated patients in the United States, using the Flatiron Health electronic health record-derived deidentified database (FHD) for advanced/metastatic non-small cell lung cancer (a/mNSCLC) and Optum's de-identified Clinformatics® Data Mart Database (CDM). Patients initiating selpercatinib treatment between 08MAY2020 and 30JUN2023 were included. We evaluated real-world time to selpercatinib treatment discontinuation or death (rwTTDd) and time to next treatment or death (rwTTNTd) using Kaplan-Meier analyses. Medication possession ratio (MPR) was estimated as a measure of medication adherence in CDM patients. In a/mNSCLC patients from the FHD (N = 68), the median rwTTDd and rwTTNTd were 22.4 [95%CI: 13.3-NR] and 21.0 [95%CI: 11.6-NR] months, respectively. In CDM, these durations were 12.1 [95%CI: 9.6-NR] and 16.2 [95%CI: 9.6-NR] months for lung cancer (n = 43), while these were not reached for thyroid cancer (n = 24) patients. The median MPR was 0.98 [IQR: 0.84-1.00] among all patients in the CDM (N = 75), with 77.3% of patients adhering (MPR ≥ 0.80) to selpercatinib. Real-world outcomes in this older and frailer patient cohort align with phase 3 trial results, further supporting selpercatinib as the standard of care for patients with RET-altered cancers. Early testing for the detection of RET alterations remains essential.

The next generation of physician-researchers: undergraduate medical students’ and residents’ attitudes, challenges, and approaches towards addressing them

BackgroundUndergraduate medical education and residency training are critical periods for conducting research. Medical diagnoses and therapies are direct results of successful research efforts that have advanced several scientific fields. This review highlights the importance of incorporating scientific research training into the curricula of undergraduate medical education and residency programs.MethodsWe utilized key databases such as PubMed, Web of Science, and Google Scholar to conduct a narrative review of English-language articles published between 2002 and 2024. Ultimately, we selected 49 studies that examined the attitudes of undergraduate medical students and residents toward research, the common challenges they encounter while participating in research activities, and the strategies that support and encourage their involvement, all in alignment with our study objectives and keywords. In addition, we identified several relevant themes, including the value of research experience in shaping well-rounded medical professionals; the integrity of research practices in residency selection, which addresses concerns such as the arms race and misrepresentation, as well as the balance between quality and quantity; striking a balance between research and clinical training while promoting equity and inclusion; and effective programs and mentorship strategies to enhance research engagement.ResultsTranslating the positive attitudes of undergraduate medical students and residents into improved knowledge and practice necessitates the development of structured mentoring programs and advanced training systems. Institutions must provide the necessary tools, guidance, and support to overcome research barriers. This will help establish an environment in undergraduate medical education and residency training that values research, facilitates access to it, and integrates it into the curriculum.ConclusionsTo address the critical shortage of physician-researchers and improve evidence-based medical practice, it is crucial for medical schools to focus on research education and create avenues for student involvement. By tackling research challenges and implementing supportive strategies, these efforts empower the next generation of physician-researchers to embrace research, contribute to medical progress, and uphold the highest standards of patient care.

BN SO13 - Re-Audit of Biliary Pancreatitis Management: Enhancing Compliance with Timely Laparoscopic Cholecystectomy

Abstract Background Biliary acute pancreatitis requires timely management to prevent complications. Guidelines recommend laparoscopic cholecystectomy within two weeks of admission. A previous audit in our surgery department showed only 32.6% compliance with this guideline. This re-audit aimed to evaluate improvements in compliance, identify barriers, and provide insights for enhancing patient care. By retrospectively analyzing patient data from January to November 2023, we assessed progress and highlighted areas needing further improvement to align with established guidelines and ensure better patient outcomes. Method A retrospective analysis was conducted on a cohort of 32 patients admitted to the general surgery department with a diagnosis of biliary acute pancreatitis between January 2023 and November 2023. Patient records were reviewed to gather data on the timing of laparoscopic cholecystectomy performed within two weeks of the index admission. The compliance rate from this period was compared to a previous audit to assess improvements. Key barriers to timely intervention, such as the availability of ultrasound slots, hot gallbladder lists, and pre-assessment clinics, were also identified and analyzed. Statistical methods were used to confirm the significance of observed changes. Results he re-audit revealed a significant improvement in compliance with guidelines for the management of biliary acute pancreatitis. The percentage of patients undergoing laparoscopic cholecystectomy within two weeks of admission increased from 32.6% in the initial audit to 64.5% in the re-audit. However, the analysis identified persistent barriers to timely intervention, including limited availability of ultrasound slots, insufficient "hot gallbladder" surgical lists, and fear of difficulty of acute laparoscopic cholecystectomy. These findings highlight both the progress made and the areas needing further attention to enhance compliance and patient care. Conclusion The re-audit demonstrated a notable improvement in adherence to guidelines for the management of biliary acute pancreatitis, with a significant increase in timely laparoscopic cholecystectomy. Despite this progress, persistent barriers such as limited ultrasound availability, insufficient "hot gallbladder" lists, and pre-assessment clinics need to be addressed. Continuous evaluation and targeted interventions are essential to further enhance compliance, reduce complications, and improve patient outcomes. Ongoing efforts to refine clinical practices will help achieve the highest standards of care for patients with biliary pancreatitis.

The European Rare Kidney Disease Reference Network

Rare kidney diseases encompass awide range of congenital, inherited and acquired conditions. Two million Europeans are affected by rare kidney diseases. The European Rare Kidney Disease Reference Network (ERKNet) aims to improve the clinical management of patients with these diseases. ERKNet encompasses 95highly specialized adult and pediatric nephrology units at 72sites in 24European Union (EU) member states, as well as agroup of patient advocates (European Patient Advocacy Group, ePAG). ERKNet centers care for more than 65,000 rare kidney disease patients and pursues avariety of activities. An online consultation service helps improve the management of complex cases. Expert working groups develop clinical practice guidelines for individual groups of rare kidney diseases. In a3-year postgraduate program, junior physicians at ERKNet centers are trained by experts in the diagnosis and treatment of rare kidney diseases through webinars and case-based eLearning modules. Information brochures and online texts on rare kidney diseases for patients, relatives and the general public are produced and disseminated. Clinical research is supported by aEuropean Registry for Rare Kidney Diseases (ERKReg), which provides important information on demographics and disease progression and facilitates the identification of patient cohorts for therapeutic studies. In addition, the registry provides clinical performance statistics of reference centers and allows benchmarking to promote the harmonization and standardization of care for rare kidney disease patients across Europe.

HPB SO20 - Evaluating the Impact of Enhanced Recovery After Surgery Protocols Post Hepatectomy in Patients with Chronic Liver Disease: A Meta-Analysis

Abstract Background Defined criteria for the resectability of liver disease continue to be refined. In the era of enhanced recovery after surgery (ERAS), data regarding its safety and efficacy in specific patient populations is required. Patients with liver cirrhosis are particularly vulnerable, owing to both operative and peri-operative risk. However, the application of ERAS in cirrhotic patients undergoing hepatectomy is absent from the most recent ERAS Society Group recommendations from 2022. We present a meta-analysis assessing outcomes after liver resection in patients with cirrhosis following an ERAS protocol compared to standard post-operative care. Method A systematic literature search was performed using PubMed, Embase and Web of Science. Studies were included if comparing ERAS protocols versus standard post-operative care in patients undergoing liver resection in which more than 50% of the patient population had cirrhosis at time of surgery. The primary outcome analysed was overall complication rates with secondary outcomes of post-operative mortality, estimated blood loss, operation time, post-operative incidence of liver failure, readmission and reoperation rates. Statistical analysis was performed using Review Manager by the Cochrane Collaboration. Results 930 records were screened for eligibility. Five articles were eligible for inclusion(ERAS n = 425 vs control group n = 423 patients). Cirrhotic patients enrolled in an ERAS program post-hepatectomy had a significantly reduced risk of overall complications (OR 0.45, 95% CI 0.33, 0.61, p<0.00001) and a shorter hospital stay when compared to standard post-operative care by 1.8 days (mean difference -1.83, 95% CI -2.22, -1.45, p<0.00001). No significant differences were noted in post-operative mortality, estimated blood loss, operation time, post-operative incidence of liver failure, readmission or reoperation rates between the ERAS group and control. Conclusion Application of an ERAS protocol for patients undergoing liver resection is safe and feasible in cirrhotic patients. ERAS protocols were successful in significantly reducing overall complication rates and length of inpatient hospital stay, and did not negatively impact secondary post-operative outcomes or mortality. ERAS protocols should be reflected in future guidelines, specifically for cirrhotic patients undergoing hepatectomy, and additional research on the utility of ERAS in higher risk patients is encouraged.

Expert Opinion for Defining a Severe Bleeding Phenotype to Guide Prophylaxis in Patients with Nonsevere Hemophilia.

Prophylaxis is the standard of care for patients with severe hemophilia, patients with moderate hemophilia, or those with another congenital bleeding disorder that is associated with a severe bleeding phenotype and/or a high risk of spontaneous life-threatening bleeding. Patients with nonsevere hemophilia (factor VIII [FVIII] ≥ 1%) may also have a bleeding phenotype that requires prophylaxis. To date, however, there are no clear criteria as to when prophylaxis is indicated in these patients. Also, the term "severe bleeding phenotype (SBPT)" is neither included in the definitions of the International Society on Thrombosis and Haemostasis (ISTH) nor specified in the World Federation of Hemophilia (WFH) guidelines. Based on our personal experience and available evidence, we propose the criteria we use to define an SBPT and when we consider offering prophylaxis in patients with nonsevere hemophilia. Our proposals can be the basis for discussions in the community about the assessment of SBPT and the initiation of prophylaxis in patients with nonsevere hemophilia without inhibitors.

Association of phenylalanine and tyrosine metabolism with mortality and response to nutritional support among patients at nutritional risk: a secondary analysis of the randomized clinical trial EFFORT.

Elevated phenylalanine serum level is a surrogate marker of whole-body proteolysis and has been associated with increased mortality in critically ill patients. Tyrosine is a metabolite of phenylalanine and serves as a precursor of thyroid hormones and catecholamines with important functions in the oxidative stress response among others. Herein, we examined the prognostic significance of phenylalanine, tyrosine, as well as its metabolites nitrotyrosine, L-3,4-dihydroxyphenylalanine (DOPA), and dopamine regarding clinical outcomes and response to nutritional therapy in patients at nutritional risk. This is a secondary analysis of the Effect of Early Nutritional Support on Frailty, Functional Outcomes, and Recovery of Malnourished Medical Inpatients Trial (EFFORT), a randomized controlled trial investigating individualized nutritional support compared to standard care in patients at risk of malnutrition. The primary outcome was 30-day all-cause mortality. We analyzed data of 238 patients and found a significant association between low plasma levels of phenylalanine [adjusted HR 2.27 (95% CI 1.29 to 3.00)] and tyrosine [adjusted HR 1.91 (95% CI 1.11 to 3.28)] with increased 30-day mortality. This association persisted over a longer period, extending to 5 years. Additionally, trends indicated elevated mortality rates among patients with low nitrotyrosine and high DOPA and dopamine levels. Patients with high tyrosine levels showed a more pronounced response to nutritional support compared to patients with low tyrosine levels (HR 0.45 versus 1.46, p for interaction = 0.02). In medical inpatients at nutritional risk, low phenylalanine and tyrosine levels were associated with increased short-and long-term mortality and patients with high tyrosine levels showed a more pronounced response to nutritional support. Further research is warranted to gain a deeper understanding of phenylalanine and tyrosine pathways, their association with clinical outcomes in patients at nutritional risk, as well as their response to nutritional therapy. www.clinicaltrials.gov, identifier NCT02517476.

Satisfactory outcomes following a second autologous hematopoietic cell transplantation for multiple myeloma in poor stem cell mobilizers: a retrospective study on behalf of the Chronic Malignancies Working Party of the EBMT.

Autologous hematopoietic cell transplants (auto-HCTs) remain the standard of care for transplant-eligible MM patients. The general practice has been to undergo upfront apheresis following induction to collect sufficient number of CD34+ cells to facilitate two auto-HCTs. However, 5-30% of MM patients do not initially mobilise a sufficient number of hematopoietic stem cells and are classified as poor mobilizers (PM). We compared the baseline characteristics and outcomes of 61 PMs and 816 non-PM patients who underwent a second auto-HCT and who were enrolled in the non-interventional CALM study (NCT01362972). Only patients who collected CD34+ prior to auto-HCT1 were included. Auto-HCT2 comprised both tandem and salvage transplants. PMs were re-mobilized with plerixafor (n = 24, 39.3%) or non-plerixafor-based regimens (n = 37, 60.7%). There were no significant differences in engraftment, progression-free survival (PFS) or overall survival (OS) after the second auto-HCT between PM and non-PM patients. There was a trend to shorter PFS in PM patients undergoing salvage auto-HCT (median 9.6 vs. 12.9 months; p = 0.08) but no significant difference in OS. The median OS was 41.1 months for PM and 41.2 months for non-PM patients (p = 0.86). These data suggest that salvage mobilization is effective and does not affect overall outcomes after a second auto-HCT.

PRO-P: evaluating the effect of electronic patient-reported outcome measures monitoring compared with standard care in prostate cancer patients undergoing surgery—study protocol for a randomized controlled trial

BackgroundWith over 65,000 new cases per year in Germany, prostate cancer (PC) is the most common cancer in men in Germany. Localized PC is often treated by radical prostatectomy and has a very good prognosis. Postoperative quality of life (QoL) is significantly influenced by the side effects of surgery. One possible approach to improve QoL is postoperative symptom monitoring using ePROMs (electronic patient-reported outcome measures) to accurately identify any need for support.MethodsThe PRO-P (“Influence of ePROMS in surgical therapy of PC on the postoperative course”) study is a randomized controlled trial employing 1:1 randomization at 6 weeks postoperatively, involving 260 patients with incontinence (≥ 1 pad/day) at six participating centers. Recruitment is planned for 1 year with subsequent 1-year follow-up. PRO-monitoring using domains of EPIC-26, psychological burden, and QoL are assessed 6, 12, 18, 24, 36, and 52 weeks postoperatively. Exceeding predefined PRO-score cutoffs triggers an alert at the center, prompting patient contact, medical consultation, and potential interventions. The primary endpoint is urinary continence. Secondary endpoints refer to EPIC-26 domains, psychological distress, and QoL. Aspects of feasibility, effect, and implementation of the intervention will be investigated within the framework of a qualitative process evaluation.DiscussionPRO-P investigates the effect on postoperative symptom monitoring of a structured follow-up using ePROMs in the first year after prostatectomy. It is one of the first studies in cancer surgery investigating PRO-monitoring and its putative applicability to routine care. Patient experiences with intensified monitoring of postoperative symptoms and reflective counseling will be examined in order to improve primarily urinary continence, and secondly other burdens of physical and psychological symptoms, quality-of-life, and patient competence. The potential applicability of the intervention in clinical practice is facilitated by IT adaption to the certification standards of the German Cancer Society and the integration of the ePROMs survey via a joint patient portal. Positive outcomes could readily translate this complex intervention into routine clinical care. PRO-P might improve urinary incontinence and QoL in patients with radical prostatectomy through the structured use of ePROMs.Trial registrationClinicalTrials.gov NCT05644821. Registered on 09 December 2022.

Role of immunohistochemical prognostic factors in various types of immunotherapy for metastatic melanoma: A retro-prospective study

Background. Anti-PD-1 immunotherapy (IT) is the standard of care for patients with metastatic melanoma. However, in the real world, IT is effective only in a fraction of patients. The lack of valid prognostic factors for various immunotherapy agents warrants a comprehensive and advanced study of this topic. Aim. To improve the outcomes of the first-line therapy for disseminated melanoma based on identifying immunohistochemical predictors of IT efficacy. Materials and methods. Data from 130 patients who were treated with immune checkpoint inhibitors nivolumab or prolgolimab in the first-line therapy for disseminated melanoma between 2017 and 2024 were analyzed. Results. The expression of PD-L110 on tumor cells was found to be a predictor of effective therapy: in the nivolumab group, the 2-year disease-free survival (DFS) with PD-L1 level 10% was high at 79% (95% confidence interval – CI 61–100); the 1-year DFS was 89% (95% CI 78–100) compared to 17% (95% CI 3.2–88) with a lower level of PD-L1 expression (p0.0001). In the prolgolimab group, the 2-year DFS with PD-L110% was also high at 78% (p0.0001; CI 54–100), the 1-year DFS was 94% (95% CI 84–100) compared to 35% (95% CI 17–73) with a lower level of PD-L1 expression (p0.0001). A less severe course of the disease was observed in patients with both peritumoral and intratumoral locations versus those with only peritumoral locations of the immune infiltrate. The study of the presence and form of lymphoid infiltration of the tumor showed the following direct relationship: in the nivolumab group, the 2-year DFS was 94% (95% CI 83–100) compared to 8.3% (95% CI 1.3–54), in the prolgolimab group, the 1-year DFS was 82% (95% CI 68–100) compared to 15% (95% CI 2.6–86); p0.0001. It was found that the predominance of CD8+ over CD4+ is associated with better results of IT: in the nivolumab group, the 2-year DFS was 87% (95% CI 74–100) compared to 19% (95% CI 4–91) in the absence of CD8+ predominance over CD4+; in the prolgolimab group, the 2-year DFS was 73% (95% CI 51–100) in patients with CD8+ predominance over CD4+ (p=0.0001). In patients without CD8 predominance over CD4, 2-year DFS was not achieved. The one-year DFS was 85% (95% CI 70–100) and 25% (95% CI 8.4–76), respectively; p=0.0001. Conclusion. The results of the study suggest that immunohistochemical characteristics such as a PD-L1 expression level 10%, the simultaneous presence of peri- and intratumoral lymphoid infiltration of the tumor, the ratio of the intensity of lymphoid infiltration with tumor-infiltrating lymphocytes (TILs), and the predominance of CD8+ over CD4+ can be considered predictors of IT efficacy with nivolumab and prolgolimab.

EPCO-43. DECONVOLUTION OF GLIOBLASTOMA RNA-SEQ REVEALS IMMUNE SUBPOPULATIONS PREDICTING THERAPEUTIC RESPONSE

Abstract Bulk RNA-seq is now among the standard of care for patients with newly diagnosed glioblastoma (GBM), but whether this data can predict therapeutic response is unclear. In silico deconvolution of bulk RNA-seq data allows for quantification of cell types comprising the tumor and its microenvironment. Our study tests whether cell type proportions predict therapeutic response in patients with GBM and high-grade glioma (HGG) enrolled in trials of investigational agents. 127 patients with GBM/HGG underwent post-resection/biopsy whole exome RNA-seq and reads were post-processed using standard computational pipelines. In silico deconvolution was performed using GBMDeconvoluteR, which generates cellular proportions comprising the RNA-seq reads. Multivariate Cox regression models were used to examine each cell proportion as a predictor of progression-free (PFS) and overall (OS) survival. Statistical significance was ascertained using Bonferroni correction for multiple comparisons. Among 54 patients treated with a PD-L1 inhibitor (nivolumab) and VEGF inhibitor (bevacizumab), the proportions of NK cells (p=0.0024), radial glial cells (p=0.0010), and mural cells (p=0.0025), was associated with increased PFS, while proportion of endothelial cells (p=0.0008) was associated with decreased PFS. Astrocyte (p=0.0022), macrophage (p=0.0015), NK cell (p<0.0001), and mural cell (p=0.0004) proportions were associated with longer OS, while endothelial cell proportion (p=0.0001) was associated with shorter OS. Among 21 patients treated with a tyrosine kinase inhibitor (ibrutinib) combined with radiation and temozolomide (RT/TMZ), cell proportions assessed at the time of diagnosis did not predict PFS or OS. In 52 patients with HGG treated with a JAK inhibitor (ruxolitinib) with RT/TMZ, only mural cell proportion was associated with a longer OS (p=0.0017). Our results highlight how bulk RNA-seq data can be used to predict therapeutic response. In GBM patients treated with immunotherapies, the proportion of NK cells may predict response. Further work will examine which gene programs are predictive of therapeutic response.

QLTI-05. EUROPEAN NEURO-ONCOLOGY QUALITY ASSURANCE (ENOQUA): AN EORTC BRAIN TUMOR GROUP STUDY

Abstract INTRODUCTION Neuro-Oncology, a complex and multidisciplinary field that is relatively recent, lacks well-established quality assurance measures and standards for patient care. METHODS We assessed the performance of 14 potential quality indicators across 19 EORTC Neuro-Oncology centers to validate these indicators as effective measures of quality. For each center, we abstracted records from 20 patients diagnosed with glioblastoma in 2018 who were not enrolled in an investigational study. We tested associations between patient survival, center characteristics, and the performance of these quality measures. RESULTS Most centers met several standard requirements, suggesting their potential acceptance for prospective validation. IDH expression data was universally recorded in the patients’ chart. Performing MRI within 72 hours of surgery and providing patient education for chemotherapy correlated with improved overall survival (OS). Standards met in the majority of centers were the presence of a multidisciplinary plan, a radiation plan and the extent of surgery recorded in the chart, as well as the referral for radiation within six weeks of diagnosis. Preliminary results indicate that academic centers outperformed others in most measures, although analysis is ongoing. Performance varied significantly across centers; some standards were consistently met poorly, highlighting areas needing improvement. Lack of universal acceptance of certain practices as necessary and/or important may render some standards inappropriate for further development. Final analysis will be presented at the meeting. CONCLUSION We are developing a comprehensive set of standards and measures for QA in neuro-oncology, which will require future prospective validation.

DDDR-37. OHSV AND RADIATION THERAPIES SENSITIZE GLIOBLASTOMA TO IGF1R-TARGETED THERAPY AND SYNERGIZE IN TRIPLE COMBINATION THERAPY

Abstract Glioblastoma (GBM) continues to have a dismal prognosis despite remarkable advances in the field due to both tumor-intrinsic factors (i.e., IDH1 or EGFRvIII mutations) and extrinsic factors (i.e., relating to the tumor microenvironment (TME)), necessitating therapeutic innovation. Oncolytic herpes simplex virus-1 (oHSV) is an FDA-approved therapy that has shown promising results in clinical trials; however, therapeutic efficacy is limited to a small subset of patients. Thus, elucidating both the tumor-TME interplay and feedback/feedforward tumor-cell signaling in the context of viro-immunotherapy is essential in augmenting therapeutic outcomes. We recently discovered a novel mechanism of resistance to oHSVs, in which infection increases secretion of Insulin-like growth factor 2 (IGF2), activating the Insulin-like Growth Factor-1 Receptor (IGF1R). Upregulation of the IGF1R signaling pathway in GBM is correlated with poor prognosis and has been implicated in resistance to conventional therapies including radiotherapy (RTx). Herein, we further elucidate the impact of oHSVs on IGF1R activation, demonstrating a dose-dependent enhancement of downstream signaling. While IGF1R targeting therapies (e.g., OSI-966, Picropodophyllin (PPP)) have displayed limited efficacy in clinical trials, they significantly increased oHSV-induced cytotoxicity in all tested primary GBM cells compared to either agent alone in vitro and in vivo, resulting in a dose-dependent increase in PARP and caspase 3 activity by western blot and immunohistochemistry. We further found that RTx-induced IGF1 secretion and subsequent IGF1R activation were enhanced when combined with oHSV treatment. Triple combination therapy with oHSV, IGF1R inhibition, and RTx significantly increased tumor cell killing in vitro and improved survival of orthotopic GBM tumor-bearing mice. Collectively, our study provides preclinical evidence of enhanced therapeutic efficacy of oHSVs and RTx in combination with IGF1R blockade, supporting future use of IGF1R inhibitors in combination with the standard of care and FDA-approved oHSV therapies in patients with GBM.

EPCO-27. CHROMATIN REMODELING REPROGRAMS THE TRANSCRIPTION NETWORK IN GLIOBLASTOMA

Abstract Fundamentally, cancer arises from genetic and epigenetic alterations that interplay to reprogram gene expression networks, leading to unrestrained proliferation. Glioblastoma (GBM) is the most prevalent and aggressive primary brain cancer, with a median survival of approximately one year and a 5-year survival rate of just 5%. The standard care for GBM patients has remained unchanged for decades, underscoring the need for a better understanding of GBM biology to develop more effective therapies. The relatively low genetic mutation burden in GBM highlights the significant role of epigenetic mechanisms in its pathogenesis. Our recent work shows that chromatin remodeling plays pivotal roles in GBM pathogenesis. The BRD8-driven EP400 chromatin remodeling complex maintains GBM by crippling p53-mediated tumor suppression in an unprecedented way through hijacking the histone variant H2AZ at p53 target loci, enforcing a repressive chromatin state that prevents p53-mediated transactivation. Targeting BRD8 in TP53WT GBM, which makes up ~71% of all GBM cases, enhances chromatin accessibility by evicting H2AZ. This restores p53-mediated transactivation of its targets, reestablishes cell cycle arrest, inhibits gliomagenesis, and prolongs survival in xenograft models of TP53WT GBM. Conversely, the NuRD chromatin remodeling complex driven by CHD5 governs the MYC-mediated oncogenic network to prevent gliomagenesis. Mechanistically, CHD5 forms a CHD3-containing but CHD4-independent NuRD complex that directly binds to the MYC promoter and super enhancers. Chd5 loss triggers the remodeling of chromatin, enhances chromatin accessibility at Myc loci, augments Myc expression, significantly impairs NSCs differentiation while promotes proliferation, transformation, and gliomagenesis in vivo. Furthermore, reactivating CHD5 in human GBM xenograft models significantly extends survival. Thus, our findings reveal previously unappreciated epigenetic mechanisms by which GBM cells reprogram both tumor-suppressive and oncogenic transcription networks to facilitate their outgrowth. This sheds new light on our understanding of GBM malignancy and provides promising therapeutic opportunities for treating patients with this devastating malignancy.

Recombinant Human Thyrotropin Plus Radioactive Iodine Among Patients With Thyroid Cancer

Radioactive iodine (131I or RAI) therapy has long been the standard of care for most patients with differentiated thyroid cancer (DTC) after primary surgery. However, no multicenter prospective studies have identified the optimal administered activity and stimulation method for RAI therapy in patients with intermediate-risk DTC. To compare the efficacy and safety of recombinant human thyrotropin (SNA001) with thyroid hormone withdrawal (THW) plus 3.7 GBq RAI in patients with intermediate-risk DTC. This noninferiority, open-label, phase 3 randomized clinical trial was conducted at 19 sites in China from April 16, 2020, to September 9, 2021, with a follow-up period of 8 months. Patients aged 18 to 70 years with DTC who had undergone a total or near-total thyroidectomy and had no distant metastasis were enrolled in the trial. Statistical analysis followed the full analysis and per-protocol analysis sets and was performed between November 18, 2021, and April 18, 2022. Patients were randomly assigned 1:1 to receive SNA001, 0.9 mg, intramuscular injection daily for 2 days or to undergo thyroid hormone withdrawal for 3 to 6 weeks. The primary end point was the success rate after 6 to 8 months of RAI therapy. Success was defined as a negative diagnostic whole-body scan result and a stimulated thyroglobulin level less than 1.0 ng/mL. A total of 307 patients (192 females [62.5%]; median [range] age, 40 [19-69] years) were randomized: 154 to the SNA001 group and 153 to the THW group. Baseline characteristics were evenly matched between the 2 groups. Noninferiority in the success rate of RAI therapy between groups was met, with success rates of 43.8% in the SNA001 group and 47.1% in the THW group (risk difference, -3.3; 95% CI, -14.8 to 8.3 percentage points). Forty-six patients (29.9%) in the SNA001 group reported adverse events compared with 90 (58.8%) in the THW group during RAI therapy (P < .001). No treatment-related adverse events leading to discontinuation and drug modification occurred in the SNA001 group. This randomized clinical trial showed that SNA001 was noninferior to THW plus 3.7 GBq RAI in patients with predominantly intermediate-risk DTC. SNA001 also demonstrated a favorable safety profile compared with THW and had a lower incidence of adverse events. Chinese Clinical Trial Registry Identifier: ChiCTR2100046907.

Effects of single- and double-shift work on hand and cognitive functions in nurses.

This study aims to examine the influence of single and double-shift work schedules on hand function and cognitive capacities, specifically working memory, attention, and response time in nurses. Shift work, particularly in extended formats, is known to affect various physical and cognitive functions critical to nursing duties. Understanding these impacts is vital for managing nurse schedules to minimize health risks and maximize performance. With an increase in demands on healthcare systems, nurses often endure prolonged working hours, which may impair their cognitive and manual abilities, thereby affecting patient care quality. This study involved 45 nurses aged 20-40 years from shift-oriented units providing direct patient care. Hand function was assessed using the Nine-Hole Peg Test (9-HPT). Cognitive functions such as working memory, attention, and response time were evaluated using the digit span task and the Stroop test, respectively. Two-way analysis of variance (ANOVA) was used for statistical analysis, assessing the interactions of time and shift type, with a significance level set at p<0.05. The results revealed significant changes in all tested variables between pre- and post-shift assessments and between single and double-shift conditions. Notably, the double-shift work significantly exacerbated declines in all measured functions. These findings suggest that double shifts may intensify the deterioration of essential nursing skills, potentially compromising patient care. This study underscores the detrimental effects of extended shift work on nurses' cognitive and manual functions. These insights should guide healthcare institutions in revising nurse scheduling practices to safeguard their well-being and maintain high standards of patient care.