bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementation of value-based healthcare in ophthalmology: a scoping review
Authors: Abubakar Zulkarnain , Sjaaf Amal Chalik , Gondhowiardjo Tjahjono Darminto , Giffari Makkaraka Moh Anfasa 
Published: March 2024

ObjectiveThis review aimed to identify and summarise how value-based healthcare (VBHC) is implemented in the field of ophthalmology.MethodsA scoping review was conducted by searching empirical and non-empirical articles from from electronic databases (PubMed, Science Direct, ProQuest and Scopus) and other methods starting January 2006 (the year Porter and Teisberg introduced VBHC) up to 31 December 2023.Results1.081 records were screened, and 12 articles (8 empirical studies and 4 non-empirical articles) were used for data extraction. Most articles were published in the UK. Most articles described the implementation of VBHC agenda by measuring outcomes and costs. All the included empirical studies reported implementation effect; otherwise, non-empirical articles were only described proposed implementation.ConclusionThe implementation of VBHC in ophthalmology has shown a positive impact on enhancing patient value and reducing healthcare costs. Nevertheless, the study highlighted that no provider or healthcare system has fully embraced and implemented VBHC, comprehensively addressing the entire value agenda.
Measuring evidence-based clinical guideline compliance in the paediatric intensive care unit
Authors: Hay Rebecca E , Martin Dori-Ann , Rutas Gary J , Jamal Shelina M , Parsons Simon J 
Published: March 2024

BackgroundEvidence-based clinical care guidelines improve medical treatment by reducing error, improving outcomes and possibly lowering healthcare costs. While some data exist on individual guideline compliance, no data exist on overall compliance to multiple nuanced guidelines in a paediatric intensive care setting.MethodsGuideline compliance was observed and measured with a prospective cohort at a tertiary academic paediatric medical-surgical intensive care unit. Adherence to 19 evidence-based clinical care guidelines was evaluated in 814 patients, and reasons for non-compliance were noted along with other associated outcomes.Measurements and main resultsOverall facility compliance was unexpectedly high at 77.8% over 4512 compliance events, involving 826 admissions. Compliance varied widely between guidelines. Guidelines with the highest compliance were stress ulcer prophylaxis (97.1%) and transfusion administration such as fresh frozen plasma (97.4%) and platelets (94.8%); guidelines with the lowest compliance were ventilator-associated pneumonia prevention (28.7%) and vitamin K administration (34.8%). There was no significant change in compliance over time with observation. Guidelines with binary decision branch points or single-page decision flow diagrams had a higher average compliance of 90.6%. Poor compliance was more often observed with poor perception of guideline trustworthiness and time limitations.ConclusionsMeasuring guideline compliance, though onerous, allowed for evaluation of current clinical practices and identified actionable areas for institutional improvement.
Evaluation of a medical after-care intervention among deselected elite male Academy football players: a pilot study
Authors: Carmody Sean , Ranson Joe , Iqbal Zafar , Massey Andrew , Kerkhoffs Gino , Gouttebarge Vincent 
Published: March 2024

ObjectiveThis pilot study aimed to evaluate the perception and satisfaction of deselected male Academy professional footballers towards a medical after-care intervention.MethodsA quasiexperimental study design, with deselected players (aged≥18 years) at a single Premier League Academy during the 2022/2023 season, were invited to participate. The intervention included individualised health recommendations, key medical information and signposting to key support resources. Participants’ perceptions and satisfaction were assessed through an electronic survey. Descriptive analyses (mean, SD, frequency and/or range) were performed for all variables.ResultsTwelve out of 15 eligible participants (80% response rate) provided informed consent and completed the survey (mean age: 19.5 years). All (100%) of the participants were satisfied with receiving the medical information. Ten out of 12 (83.3%) participants agreed that all Academy players should receive this medical intervention on deselection. Nine (75%) players felt more prepared for the next steps in their careers due to the medical information shared with them.ConclusionDeselected male Academy footballers expressed high satisfaction with an individualised medical intervention which shared key health information and signposted them to important resources (eg, mental health). Future studies across multiple clubs should explore the broader impact of this intervention among deselected male and female Academy footballers. Football clubs should consider integrating a medical after-care process for deselected players as part of routine care.
Absence of a pancreatic microbiome in intraductal papillary mucinous neoplasm
Authors: Pust Marie-Madlen , Rocha Castellanos Darío Missael , Rzasa Kara , Dame Andrea , Pishchany Gleb , Assawasirisin Charnwit , Liss Andrew , Fernandez-del Castillo Carlos , Xavier Ramnik J 
Published: March 2024

Objective
This study aims to validate the existence of a microbiome within intraductal papillary mucinous neoplasm (IPMN) that can be differentiated from the taxonomically diverse DNA background of next-generation sequencing procedures.

Design
We generated 16S rRNA amplicon sequencing data to analyse 338 cyst fluid samples from 190 patients and 19 negative controls, the latter collected directly from sterile syringes in the operating room. A subset of samples (n=20) and blanks (n=5) were spiked with known concentrations of bacterial cells alien to the human microbiome to infer absolute abundances of microbial traces. All cyst fluid samples were obtained intraoperatively and included IPMNs with various degrees of dysplasia as well as other cystic neoplasms. Follow-up culturing experiments were conducted to assess bacterial growth for microbiologically significant signals.

Results
Microbiome signatures of cyst fluid samples were inseparable from those of negative controls, with no difference in taxonomic diversity, and microbial community composition. In a patient subgroup that had recently undergone invasive procedures, a bacterial signal was evident. This outlier signal was not characterised by higher taxonomic diversity but by an increased dominance index of a gut-associated microbe, leading to lower taxonomic evenness compared with the background signal.

Conclusion
The ‘microbiome’ of IPMNs and other pancreatic cystic neoplasms does not deviate from the background signature of negative controls, supporting the concept of a sterile environment. Outlier signals may appear in a small fraction of patients following recent invasive endoscopic procedures. No associations between microbial patterns and clinical or cyst parameters were apparent.
Impact of the time of initiation and line of biologic therapy on the retention rate of secukinumab in axial spondyloarthritis (axSpA): data from the French multicentre retrospective FORSYA study
Authors: Dougados Maxime , Lardy-Cléaud Audrey , Desfleurs Emilie , Claudepierre Pascal , Goupille Philippe , Ryussen-Witrand Adeline , Saraux Alain , Tournadre Anne , Wendling Daniel , Lukas Cédric 
Published: March 2024

ObjectiveTo compare the 1-year retention rate of secukinumab in axial spondyloarthritis (axSpA) and its predisposing factors with regard to its time of initiation (eg, right after or remotely from its launch).MethodsStudy design: Retrospective multicentre French study of patients with axSpA. Study periods: Two cohorts were evaluated regarding the time of initiation of secukinumab: cohort 1 (C1)—between 16 August 2016 and 31 August 2018—and cohort 2 (C2)—between 1 September 2018 and 13 November 2020. Statistical analysis: The 1-year retention rate of secukinumab was estimated using the Kaplan-Meier method, and the log-rank test was used to compare the retention curves of the two cohorts. Preselected factors (eg, disease characterristics, line and time of secukinumab initiation) of secukinumab retention at 1 year were analysed by univariate and multivariate Cox model regression.ResultsIn total, 906 patients in C1 and 758 in C2 from 50 centres were included in the analysis. The 1-year retention rate was better in C2 (64% (61%–68%)) vs C1 (59% (55%–62%)) (HR=1.19 (1.02–1.39); p=0.0297). In the multivariate analysis, the line of biologic therapy was the single predictive factor of the 1-year retention rate of secukinumab picked up in both cohorts, with a better retention rate when prescribed as first-line biologic therapy.ConclusionThe better secukinumab retention rate remotely from its launch is explained by its use at an earlier stage of the disease, suggesting a change in the behaviour of prescribing physicians. Our results emphasise the relevance of iterative evaluations of routine care treatments.
Post-urethroplasty complications in hypospadias repair: a systematic review and meta-analysis comparing polydioxanone and polyglactin sutures
Authors: Borkar Nitinkumar , Tiwari Charu , Mohanty Debajyoti , Baruah Tridip Dutta , Mohanty Manoj , Sinha C K 
Published: March 2024

BackgroundPolyglactin (PG) and polydioxanone (PDS) sutures are extensively used based on the surgeon’s preference. The development of post-reconstruction urethrocutaneous fistula (UCF) is variably attributed to the choice of suture material for urethroplasty. This meta-analysis compares complications of hypospadias repair using PG and PDS sutures.MethodsThe systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The authors conducted thorough searches in databases including MEDLINE, EMBASE, CENTRAL, Scopus, Google Scholar, and clinical trial registries. Outcome measures included UCF, meatal stenosis, wound infection, urethral stricture, glans dehiscence, and overall complications. Quantitative analysis was used with fixed or random-effect models to find the pooled risk ratio and I2heterogeneity.ResultsThe criteria for inclusion were met by five comparative studies with the inclusion of 1244 children altogether. Pooled analysis failed to show a statistically significant difference in the incidence of meatal stenosis, urethral stricture, wound infection, and total complications using PG and PDS sutures. However, it showed a reduction in the incidence of UCF with PDS suture hypospadias repairs (risk ratio=0.66, 95% CI 0.48 to 0.92).ConclusionsPDS sutures are associated with decreased incidence of UCF than PG after hypospadias repair. The incidence of meatal stenosis, urethral stricture, wound infection, and total complications was not affected by the type of suture material used for repair.Clinical implicationsThis meta-analysis suggests decreased incidence of UCF when PDS sutures are used for hypospadias repair which may impact the choice of suture material for repair.PROSPERO registration numberCRD42023409710.
Abstract A018: A phase 2, open-label, single-arm, prospective, multicenter study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer
Authors: Dockery Lauren E. , Priebe Anna , Duska Linda , Green Angela K. , Mathews Cara , Musa Fernanda , O'Malley David , Puechl Allison , Ding Li , Schmid Anita N. , Navarro Willis H. , Slomovitz Brian , Moore Kathleen 
Published: March 2024

Abstract
Introduction/Objective: This trial in progress is designed to evaluate the anti-tumor activity of nab-sirolimus in combination with letrozole in patients with advanced or recurrent endometrioid endometrial carcinoma (EEC). Despite recent pivotal data demonstrating improved outcomes with immunotherapy plus chemotherapy, regardless of mismatch repair status, alternative treatment options, particularly for advanced or recurrent EEC remain necessary. Dysregulation of mammalian target of rapamycin (mTOR) signaling is implicated in the pathology of EEC, in which &gt;80% harbor PTEN or PI3K/AKT/mTOR pathway alterations. Moreover, crosstalk between mTOR and estrogen receptor signaling pathways is associated with endocrine resistance. GOG-3007 and other phase 2 studies have demonstrated that the combination of conventional mTOR inhibitors (mTORis) and endocrine therapy provides clinical benefit in patients with EC. nab-Sirolimus, a nanoparticle injectable form of mTORi, is approved in the USA for malignant perivascular epithelioid cell tumor. Preclinical data of nab-sirolimus demonstrated improved tumor accumulation, mTOR inhibition, and tumor growth suppression compared with conventional mTORis. We hypothesize that nab-sirolimus in combination with letrozole may produce synergistic antitumor activity in patients with recurrent EEC. Methods: In this phase 2, open-label, single-arm, multicenter study (NCT05997017), nab-sirolimus (100 mg/m2, intravenous, on days 1 and 8 of each 21-day cycle) and letrozole (2.5 mg, oral, daily) are administered to patients (~29 planned) with clinically confirmed, advanced, or recurrent EEC. Eligibility criteria include age ≥18 years, ≤1 prior chemo-based regimen, Eastern Cooperative Oncology Group performance status score 0 or 1, naïve to mTORi, and measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1). The primary endpoint is best overall response rate by RECIST v1.1. Key secondary endpoints include duration of response, progression-free survival, overall survival, and safety. The relationship between biomarkers and response outcomes is an exploratory endpoint.
Citation Format: Lauren E. Dockery, Anna Priebe, Linda Duska, Angela K. Green, Cara Mathews, Fernanda Musa, David O'Malley, Allison Puechl, Li Ding, Anita N. Schmid, Willis H. Navarro, Brian Slomovitz, Kathleen Moore. A phase 2, open-label, single-arm, prospective, multicenter study of nab-sirolimus plus letrozole in advanced or recurrent endometrioid endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr A018.
Abstract B014: Patient-derived organoid models for drug screening in molecular subtypes of endometrial cancer
Authors: Liu Dongli , Powell Elyse , Wan King Man , Athavale Ramanand , Loo Christine , Ford Caroline E. 
Published: March 2024

Abstract
Introduction: The lack of reliable pre-clinical models has significantly impeded the progress of drug discovery for specific molecular subtypes of endometrial cancer. This study aimed to develop patient-derived organoid models for use in preclinical screening of novel and repurposed therapies in endometrial cancer molecular subtypes. Method: Endometrial cancer tissue (n=27) and ascites fluid (n=1) were collected for this study (ethics approval SESLHD HREC 2021_ETH11975 and 19/001) from patients of various subtypes (17 endometrioid, 3 high grade serous, 2 carcinosarcoma, 2 clear cell, 3 mixed) undergoing treatment at the Royal Hospital for Women and Prince of Wales Private Hospital in Sydney, Australia. Tumor cells were isolated, embedded in 70% Matrigel and cultured in defined culture medium to form organoids. Molecular subtyping of organoids and matched parental tissue was undertaken by mismatch repair (MMR) and p53 immunohistochemistry (IHC), and sequencing of POLE exonuclease domain mutations (EDMs). A unique matched two-dimensional (2D) cell line and three-dimensional (3D) organoid culture derived from ascites isolated from a high grade serous endometrial cancer patient was established. These molecularly stratified pre-clinical models were then used to test drug activity. As a proof of principle, response to paclitaxel and carboplatin was undertaken. Result: 20 organoids representing all major molecular subtypes were established (71% success rate), including one derived from ascites fluid. Organoids are presented with either a cystic or solid structure that highly resembles the morphology of the original tissue. Organoid culture can faithfully retain key features including MMR, p53 status as well as POLE EDMs of the parental tissue. The drug screening results identified contrasting responses of 2D and 3D models obtained from the same patient tissue, highlighting the importance of selecting appropriate pre-clinical models for drug development and testing. Conclusion: This study demonstrated that patient-derived organoids can successfully recapitulate the molecular characterization of endometrial cancer. Molecularly defined organoids represent a promising preclinical resource for drug screening in endometrial cancer. In addition, the model structure should be taken into account while conducting drug screening.
Citation Format: Dongli Liu, Elyse Powell, King Man Wan, Ramanand Athavale, Christine Loo, Caroline E. Ford. Patient-derived organoid models for drug screening in molecular subtypes of endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B014.
Abstract B018: MYC is sufficient to generate mid-life high-grade serous ovarian and serous endometrial carcinomas in a BRCA wild type p53-R270H mouse model
Authors: Blackman Alexandra , Rees Amy , Bowers Rob , Jones Christian , Vaena Silvia , Carter Shelby , Villamor Evan , Evans Della , Fullbright George , Long David , Spruill Laura , Romeo Martin , Helke Kristi , Emanuel Anthony , Delaney Joe 
Published: March 2024

Abstract
Genetically engineered mouse models (GEMM) have fundamentally changed how cancer etiology, early detection, and treatment can be understood. Mouse models have been developed that support the fallopian tube as the origin of some ovarian cancers. However, serous endometrial cancer is a much rarer gynecologic cancer with fewer models available. The genetics of serous endometrial cancer are very similar that of high-grade serous ovarian cancer. The most common mutation found in both high-grade serous ovarian cancer and serous uterine cancer is p53 and in humans, MYC is amongst the most amplified genes in both tyeps of cancer. We developed a GEMM of high-grade serous ovarian cancer by using a fallopian tube epithelium specific promoter Ovgp1 to express MYC and dominant negative mutant p53-R270H. Female mice developed lethal cancer at an average of 15.1 months. Histopathological examination of mice revealed HGSOC characteristics including nuclear p53 and nuclear MYC in clusters of cells within the fallopian tube epithelium and ovarian surface epithelium. Unexpectedly, nuclear p53 and MYC clustered cell expression was also identified in the uterine luminal epithelium, possibly from intraepithelial metastasis from the fallopian tube epithelium. Extracted tumor cells exhibited strong loss of heterozygosity at the p53 locus, leaving the mutant allele. Copy number alterations in these cancer cells were prevalent, disrupting a large fraction of genes. Transcriptome profiles most closely matched human HGSOC and serous endometrial cancer. Histological and transcriptomic findings are consistent with the hypothesis that serous uterine cancer may originate from the fallopian tube epithelium.
Citation Format: Alexandra Blackman, Amy Rees, Rob Bowers, Christian Jones, Silvia Vaena, Shelby Carter, Evan Villamor, Della Evans, George Fullbright, David Long, Laura Spruill, Martin Romeo, Kristi Helke, Anthony Emanuel, Joe Delaney. MYC is sufficient to generate mid-life high-grade serous ovarian and serous endometrial carcinomas in a BRCA wild type p53-R270H mouse model [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B018.
Abstract B020: A clinically relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids
Authors: Gorman Megan , Gowthaman Divya , Katcher Arielle , Chung Charlie , Yueh Brian , Barbi Mali , Garcia Libia , Frimer Marina , Goldberg Gary L. , Beyaz Semir 
Published: March 2024

Abstract
Uterine carcinosarcoma (CS) is a rare but aggressive endometrial malignancy. The incidence of CS has been increasing and is projected to continue to rise. African American women in particular have an increased incidence of CS and overall increased mortality related to endometrial cancer, underscoring known disparities in cancer care across racial and ethnic groups. Compared to other histologic subtypes, CS remains rare and understudied on a molecular and cellular basis, and under-represented in clinical trials. Therefore, current treatment therapies available for CS have been extrapolated from treatments used in other histologies of endometrial cancer, highlighting a significant need for effective treatment targeted at this subtype. Due to this paucity of data surrounding targeted therapies for CS, patients who are diagnosed with this aggressive and lethal cancer tend to have worse outcomes. We have developed a clinically relevant CS murine model by injecting human CS patient-derived organoids (PDO) from diverse ancestries into the endometrium of immunocompromised mice. Tumor progression in the mice was monitored with physical examination, PET/CT scan, contrast enhanced CT scan, ultrasound, and bioluciferase imaging. The tumor was established after three months, and the mice were sacrificed following the experiment. The diagnosis of invasive CS was confirmed by macroscopic and histologic analyses in the orthotopic model. Our orthotopic CS PDO transplantation model has many potential applications for studying tumor biology of CS in the pre-clinical setting. Future directions include trialing the efficacy of standard of care chemotherapy in the orthotopic model. Using this model, we aim to identify targeted therapy for CS and potentially advance to Phase I human clinical trials.
Citation Format: Megan Gorman, Divya Gowthaman, Arielle Katcher, Charlie Chung, Brian Yueh, Mali Barbi, Libia Garcia, Marina Frimer, Gary L. Goldberg, Semir Beyaz. A clinically relevant orthotopic endometrial carcinosarcoma mouse model using human patient-derived organoids [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B020.
Abstract IA003: The future of endometrial cancer research: possibility and purpose
Authors: Doll Kemi 
Published: March 2024

Abstract
This talk will review the growing problem of endometrial cancer in the United States, discussing the state of the science, ongoing investigations, and promises of future progress along the entire endometrial cancer care continuum. An emphasis on health equity, workforce diversity, and patient-centeredness will be included.
Citation Format: Kemi Doll. The future of endometrial cancer research: possibility and purpose [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr IA003.