bluuebunny/crossref_metadata_2025 huggingface dataset:
A decade of change towards Value-Based Health Care at a Dutch University Hospital: a complexity-informed process study
Authors: van Engen Veerle , Buljac-Samardzic Martina , Baatenburg de Jong Rob , Braithwaite Jeffrey , Ahaus Kees , Den Hollander-Ardon Monique , Peters Ingrid , Bonfrer Igna
Published: August 2024

Background

While healthcare organizations in several countries are embracing Value-Based Health Care (VBHC), there are limited insights into how to achieve this paradigm shift. This study examines the decade-long (2012–2023) change towards VBHC in a pioneering Dutch university hospital.

Method

Through retrospective, complexity-informed process research, we study how a Dutch university hospital’s strategy to implement VBHC evolved, how implementation outcomes unfolded, and the underlying logic behind these developments. Data include the hospital’s internal documents (n = 10,536), implementation outcome indicators (n = 4), a survey among clinicians (n = 47), and interviews with individuals contributing to VBHC at the hospital level (n = 20).

Results

The change towards VBHC is characterized by three sequential strategies. Initially, the focus was on deep change through local, tailored implementation of multiple VBHC elements. The strategy then transitioned to a hospital-wide program aimed at evolutionary change on a large scale, emphasizing the integration of VBHC into mainstream IT and policies. Recognizing the advantages and limitations of both strategies, the hospital currently adopts a “hybrid” strategy. This strategy delicately combines deep and broad change efforts. The strategy evolved based on accumulated insights, contextual developments and shifts in decision-makers. The complexity of change was downplayed in plans and stakeholder communication. By the end of 2023, 68 (sub)departments engaged in VBHC, enabled to discuss patients’ responses to Patient Reported Outcomes Measures (PROMs) during outpatient care. However, clinicians’ use of PROMs data showed limitations. While pioneers delved deeper into VBHC, laggards have yet to initiate it.

Conclusions

VBHC does not lend itself to linear planning and is not easily scalable. While there appears to be no golden standard for implementation, blending local and larger-scale actions appears advantageous. Local, deep yet harmonized and system-integrated changes culminate in large scale transformation. Embracing complexity and focusing on the ultimate aims of (re)institutionalization and (re)professionalization are crucial.
Integrating knowledge graphs into machine learning models for survival prediction and biomarker discovery in patients with non–small-cell lung cancer
Authors: Fang Chao , Arango Argoty Gustavo Alonso , Kagiampakis Ioannis , Khalid Mohammad Hassan , Jacob Etai , Bulusu Krishna C. , Markuzon Natasha
Published: August 2024

Accurate survival prediction for Non-Small Cell Lung Cancer (NSCLC) patients remains a significant challenge for the scientific and clinical community despite decades of advanced analytics. Addressing this challenge not only helps inform the critical aspects of clinical study design and biomarker discovery but also ensures that the ‘right patient’ receives the ‘right treatment’. However, survival prediction is a highly complex task, given the large number of ‘omics; and clinical features, as well as the high degree of freedom that drive patient survival. Prior knowledge could play a critical role in uncovering the complexity of a disease and understanding the driving factors affecting a patient’s survival. We introduce a methodology for incorporating prior knowledge into machine learning–based models for prediction of patient survival through Knowledge Graphs, demonstrating the advantage of such an approach for NSCLC patients. Using data from patients treated with immuno-oncologic therapies in the POPLAR (NCT01903993) and OAK (NCT02008227) clinical trials, we found that the use of knowledge graphs yielded significantly improved hazard ratios, including in the POPLAR cohort, for models based on biomarker tumor mutation burden compared with those based on knowledge graphs. Use of a model-defined mutational 10-gene signature led to significant overall survival differentiation for both trials. We provide parameterized code for incorporating knowledge graphs into survival analyses for use by the wider scientific community.
Healthcare workers’ perceptions and user experiences of biometric technology in the selected healthcare facilities in Zambia
Authors: Hamapa Arnold M. , Zulu Joseph M. , Khondowe Oswell , Hangulu Lydia
Published: August 2024

Background

Biometric recognition, using traits like fingerprints, faces, and irises, has advanced significantly, enabling accurate identification. Despite progress, implementation in Zambian healthcare is limited. This study explored healthcare workers’ and patients' perceptions and experiences regarding biometric technology in Zambian healthcare settings, offering insights for informed decision-making and product design.

Methods

This phenomenological study explored the perceptions and experiences of healthcare workers and end-users (patients) concerning biometric technology in four healthcare facilities in Lusaka Province: Chilenje, Chawama, Kanyama (first-level hospitals), and Railways Urban Clinic. These facilities were purposefully selected for their active use of biometric services and involvement with the National Health Insurance Management Authority (NHIMA). The study included 20 healthcare workers and 16 patients. Face-to-face interviews with healthcare workers and patients, and focus group discussions with users, lasting 35 to 65 min, were conducted. Interviews were audio-recorded, transcribed verbatim, coded with Nvivo version 12, and analyzed using inductive thematic analysis.

Results

Facilitators included efficient system integration, investment in biometric equipment, workflow transformation, and patient recognition of benefits. Barriers included infrastructure limitations, technical challenges, patient resistance and misconceptions, and accessibility challenges for individuals with disabilities.

Conclusion

This study highlights the transformative potential of biometric identification systems in healthcare, emphasizing benefits in efficiency and data integrity. Successful integration requires addressing facilitators like education and infrastructure and mitigating barriers such as cultural resistance and technological limitations. Stakeholders, including policymakers and healthcare providers, can use these insights to align efforts with Sustainable Development Goals for improved healthcare access and reduced inequalities. Considering user perspectives is crucial for effective implementation, and continuous improvement can enhance healthcare delivery and patient outcomes.
Estimating highest capacity propulsion performance using backward-directed force during walking evaluation for individuals with acquired brain injury
Authors: LaCroix Kelli , Horelka Lauren , Hung Clif , Brown David A.
Published: August 2024

There are over 5.3 million Americans who face acquired brain injury (ABI)-related disability as well as almost 800,000 who suffer from stroke each year. To improve mobility and quality of life, rehabilitation professionals often focus on walking recovery soon after hospital discharge for ABI. Reduced propulsion capacity (force output of the lower limbs to counteract ground reaction forces) negatively impacts walking ability and complicates recovery during rehabilitation for brain injured people. We describe a method, using backward-directed resistance (BDR) in a robotic-based treadmill device, to allow measurement of maximum walking propulsion force (MWPF) that is not otherwise possible during overground walking assessment. Our objective was to test the construct validity of a maximum walking propulsion force (MWPF) measure that reflects a person’s propulsive strength against applied BDR, while walking on a robotic treadmill-based device for participants with acquired brain injury (ABI). Our study enrolled 14 participants with ABI at an in inpatient rehabilitation in Galveston, TX from 8/1/21 − 4/31/22. The range of weight-adjusted MWPF was 2.6–27.1% body weight (%BW), mean 16.5 ± 8.4%BW, reflecting a wide range of propulsive force capability. The strongest correlation with overground tests was between the 6-minute walk test (6-MWT) distance and the MWPF values (r = 0.83, p < 0.001) with moderate correlations between the 10-meter walk tests at comfortable (CWS) and fast speeds (FWS). The Five Times Sit-to-Stand (used as a standard clinical measure of functional lower extremity strength) and MWPF tests were poorly correlated (r = 0.26, p = 0.4). Forward model selection included 6-MWT distance, age, and overground CWS as significant partial predictors of MWPF. We conclude that this novel MWPF measure is a valid representation of maximum propulsive force effort during walking for people post-ABI. Additional research could help determine the impact of interventions designed to increase propulsive force generation during rehabilitation training to improve overground walking performance.
Effectiveness of de-implementation of low-value healthcare practices: an overview of systematic reviews
Authors: Kien Christina , Daxenbichler Julia , Titscher Viktoria , Baenziger Julia , Klingenstein Pauline , Naef Rahel , Klerings Irma , Clack Lauren , Fila Julian , Sommer Isolde
Published: August 2024

Background

Reducing low-value care (LVC) is crucial to improve the quality of patient care while increasing the efficient use of scarce healthcare resources. Recently, strategies to de-implement LVC have been mapped against the Expert Recommendation for Implementing Change (ERIC) compilation of strategies. However, such strategies’ effectiveness across different healthcare practices has not been addressed. This overview of systematic reviews aimed to investigate the effectiveness of de-implementation initiatives and specific ERIC strategy clusters.

Methods

We searched MEDLINE (Ovid), Epistemonikos.org and Scopus (Elsevier) from 1 January 2010 to 17 April 2023 and used additional search strategies to identify relevant systematic reviews (SRs). Two reviewers independently screened abstracts and full texts against a priori–defined criteria, assessed the SR quality and extracted pre-specified data. We created harvest plots to display the results.

Results

Of 46 included SRs, 27 focused on drug treatments, such as antibiotics or opioids, twelve on laboratory tests or diagnostic imaging and seven on other healthcare practices. In categorising de-implementation strategies, SR authors applied different techniques: creating self-developed strategies (n = 12), focussing on specific de-implementation strategies (n = 14) and using published taxonomies (n = 12). Overall, 15 SRs provided evidence for the effectiveness of de-implementation interventions to reduce antibiotic and opioid utilisation. Reduced utilisation, albeit inconsistently significant, was documented in the use of antipsychotics and benzodiazepines, as well as in laboratory tests and diagnostic imaging. Strategies within the adapt and tailor to context, develop stakeholder interrelationships, and change infrastructure and workflow ERIC clusters led to a consistent reduction in LVC practices.

Conclusion

De-implementation initiatives were effective in reducing medication usage, and inconsistent significant reductions were observed for LVC laboratory tests and imaging. Notably, de-implementation clusters such as change infrastructure and workflow and develop stakeholder interrelationships emerged as the most encouraging avenues. Additionally, we provided suggestions to enhance SR quality, emphasising adherence to guidelines for synthesising complex interventions, prioritising appropriateness of care outcomes, documenting the development process of de-implementation initiatives and ensuring consistent reporting of applied de-implementation strategies.

Registration

OSF Open Science Framework 5ruzw.
Hunger in the shadow of conflict: analyzing malnutrition and humanitarian challenges in Sudan
Authors: Mohamed Amira , Homeida Anmar
Published: August 2024

Background

Conflict has become a global reality, particularly impacting millions of children, with the majority of conflicts occurring in developing nations, where 90% of the world's children reside. The Horn of Africa, especially Sudan, has faced severe conflicts, with the year 2023 witnessing one of the toughest conflicts in the region, resulting in a high number of internally displaced persons and refugees. Children, especially in areas like Darfur, Khartoum, Gezira, and Kordofan, bear the brunt of ongoing large-scale conflicts, facing widespread human rights violations and resource damage.

Before the conflict that began in April 2023, Khartoum was home to numerous children's hospitals, but now only Elbuluk Hospital remains operational, facing a surge in admissions due to displacement and subsequent returns of civilians seeking medical care. Although malnutrition cases have increased, the case fatality rate associated with severe acute malnutrition has doubled from approximately 6% to 12% by March 2024, possibly due to uneven food distribution amid sporadic peace efforts.

Recommendations

Investing in grassroots organizations is crucial for facilitating effective humanitarian aid delivery, as they are uniquely positioned to identify and address local needs promptly and efficiently. Strengthening these organizations enhances their capacity to coordinate aid distribution and provide essential services tailored to regional conditions.

Persistent violations of International Humanitarian Law (IHL) in conflict zones impede humanitarian efforts. Robust collaboration between international and local stakeholders is necessary to uphold and enforce IHL, with a focus on protecting civilian lives and ensuring safe, unhindered access for humanitarian aid while respecting the dignity of all affected individuals.
Involvement of posterior hypothalamic CaMKII-positive neurons in ADHD-like behaviors in mice
Authors: Lee Changwoo , Woo Changsu , Ma Gyeong Ryeong , Choi Kyuhyun , Kang Shin Jung , Shin Ki Soon
Published: August 2024

This study explores the behavioral effects of modulating CaMKII-positive (CaMKII+) neurons in the posterior hypothalamus (PH). Utilizing a chemogenetic approach in mice, we discovered that the activation of CaMKII + neurons within the PH is associated with heightened locomotor activity, reduced social interaction, and impulsive behavior unrelated to anxiety or avoidance. These observed behaviors share a significant resemblance with characteristics commonly found in attention deficit and hyperactivity disorder (ADHD). Notably, treatment with clonidine, which is frequently prescribed for ADHD, effectively reduced impulsive behaviors in our mouse model. Our findings uncover the role of the PH that has not been previously explored and suggest a possible involvement of the PH in the manifestation of ADHD-like behaviors.
Small cell lung cancer: emerging subtypes, signaling pathways, and therapeutic vulnerabilities
Authors: Zhang Jing , Zeng Xiaoping , Guo Qiji , Sheng Zhenxin , Chen Yan , Wan Shiyue , Zhang Lele , Zhang Peng
Published: August 2024

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by early metastasis, rapid tumor growth and poor prognosis. In recent decades, the epidemiology, initiation and mutation characteristics of SCLC, as well as abnormal signaling pathways contributing to its progression, have been widely studied. Despite extensive investigation, fewer drugs have been approved for SCLC. Recent advancements in multi-omics studies have revealed diverse classifications of SCLC that are featured by distinct characteristics and therapeutic vulnerabilities. With the accumulation of SCLC samples, different subtypes of SCLC and specific treatments for these subtypes were further explored. The identification of different molecular subtypes has opened up novel avenues for the treatment of SCLC; however, the inconsistent and uncertain classification of SCLC has hindered the translation from basic research to clinical applications. Therefore, a comprehensives review is essential to conclude these emerging subtypes and related drugs targeting specific therapeutic vulnerabilities within abnormal signaling pathways. In this current review, we summarized the epidemiology, risk factors, mutation characteristics of and classification, related molecular pathways and treatments for SCLC. We hope that this review will facilitate the translation of molecular subtyping of SCLC from theory to clinical application.
Mapping the past with historical geographic information systems: layered characteristics of the historic urban landscape of Nanjing, China, since the Ming Dynasty (1368–2024)
Authors: Bai Xuefeng , Jiao Xinyu , Sakai Takeru , Xu Hao
Published: August 2024

The layering process of the historic urban landscape (HUL) has spatial and temporal characteristics. With the help of digital technology, building a database to collect and manage spatial information on HUL is an effective research method. Taking Nanjing since the Ming Dynasty (1368–2024) as an example, our paper proposes a framework for constructing a historical geographic information system (HGIS) for HUL. The results show that (1) ancient Chinese historical archives have good potential for use in the construction of historical landscape databases. The HGIS can visualize the evolution of HUL and realize the storage, expression, querying, and analysis of information in different formats. (2) The Republic of China is a turning point in the evolution of Nanjing’s HUL. In terms of spatial evolution, the main distribution areas of urban form and characteristic places, as well as the NACH (normalized angular choice) and NAIN (normalized angular integration) cores of the road network, all moved from the south to the north of the city. In terms of typological evolution, the urban form changes from a predominantly residential area to one that emphasizes residential, administrative, educational and industrial areas. The main types of characteristic places shifted from house gardens, temples and ancestral halls to scenic buildings and public gardens. (3) Political factors, urban planning, commercial ports, and land prices influence the layering process of the HUL. The constructed database guides the preservation of HUL from the digital heritage perspective and the construction of other historical databases with spatial characteristics.
Mechanically induced M2 macrophages are involved in bone remodeling of the midpalatal suture during palatal expansion
Authors: Li Lan , Zhai Mingrui , Cheng Chen , Cui Shuyue , Wang Jixiao , Zhang Zijie , Liu Jiani , Wei Fulan
Published: August 2024

Background

Palatal expansion is a common way of treating maxillary transverse deficiency. Under mechanical force, the midpalatal suture is expanded, causing local immune responses. This study aimed to determine whether macrophages participate in bone remodeling of the midpalatal suture during palatal expansion and the effects on bone remodeling.

Methods

Palatal expansion model and macrophage depletion model were established. Micro-CT, histological staining, and immunohistochemical staining were used to investigate the changes in the number and phenotype of macrophages during palatal expansion as well as the effects on bone remodeling of the midpalatal suture. Additionally, the effect of mechanically induced M2 macrophages on palatal osteoblasts was also elucidated in vitro.

Results

The number of macrophages increased significantly and polarized toward M2 phenotype with the increase of the expansion time, which was consistent with the trend of bone remodeling. After macrophage depletion, the function of osteoblasts and bone formation at the midpalatal suture were impaired during palatal expansion. In vitro, conditioned medium derived from M2 macrophages facilitated osteogenic differentiation of osteoblasts and decreased the RANKL/OPG ratio.

Conclusions

Macrophages through polarizing toward M2 phenotype participated in midpalatal suture bone remodeling during palatal expansion, which may provide a new idea for promoting bone remodeling from the perspective of regulating macrophage polarization.
Standard versus individualised positive end-expiratory pressure (PEEP) compared by electrical impedance tomography in neurocritical care: a pilot prospective single centre study
Authors: Spatenkova Vera , Mlcek Mikulas , Mejstrik Alan , Cisar Lukas , Kuriscak Eduard
Published: August 2024

Background

Individualised bedside adjustment of mechanical ventilation is a standard strategy in acute coma neurocritical care patients. This involves customising positive end-expiratory pressure (PEEP), which could improve ventilation homogeneity and arterial oxygenation. This study aimed to determine whether PEEP titrated by electrical impedance tomography (EIT) results in different lung ventilation homogeneity when compared to standard PEEP of 5 cmH2O in mechanically ventilated patients with healthy lungs.

Methods

In this prospective single-centre study, we evaluated 55 acute adult neurocritical care patients starting controlled ventilation with PEEPs close to 5 cmH2O. Next, the optimal PEEP was identified by EIT-guided decremental PEEP titration, probing PEEP levels between 9 and 2 cmH2O and finding the minimal amount of collapse and overdistension. EIT-derived parameters of ventilation homogeneity were evaluated before and after the PEEP titration and after the adjustment of PEEP to its optimal value. Non-EIT-based parameters, such as peripheral capillary Hb saturation (SpO2) and end-tidal pressure of CO2, were recorded hourly and analysed before PEEP titration and after PEEP adjustment.

Results

The mean PEEP value before titration was 4.75 ± 0.94 cmH2O (ranging from 3 to max 8 cmH2O), 4.29 ± 1.24 cmH2O after titration and before PEEP adjustment, and 4.26 ± 1.5 cmH2O after PEEP adjustment. No statistically significant differences in ventilation homogeneity were observed due to the adjustment of PEEP found by PEEP titration. We also found non-significant changes in non-EIT-based parameters following the PEEP titration and subsequent PEEP adjustment, except for the mean arterial pressure, which dropped statistically significantly (with a mean difference of 3.2 mmHg, 95% CI 0.45 to 6.0 cmH2O, p < 0.001).

Conclusion

Adjusting PEEP to values derived from PEEP titration guided by EIT does not provide any significant changes in ventilation homogeneity as assessed by EIT to ventilated patients with healthy lungs, provided the change in PEEP does not exceed three cmH2O. Thus, a reduction in PEEP determined through PEEP titration that is not greater than 3 cmH2O from an initial value of 5 cmH2O is unlikely to affect ventilation homogeneity significantly, which could benefit mechanically ventilated neurocritical care patients.
Improved flame retardancy and mechanical properties of bacterial cellulose fabrics via solvent exchange and entrapment of zein and gluten
Authors: Kim Hyunjin , Kim Hye Rim
Published: August 2024

This study aimed to improve the flame retardancy and mechanical properties of bacterial cellulose (BC) by introducing cereal proteins, namely zein and gluten. The production conditions were determined by observing residual masses of samples at 1000 ℃ using thermogravimetric analysis (TGA). According to the TGA results, the optimized production conditions for the BCs with zein and gluten were combined solvent exchange and entrapment of 20 weight% (wt.%) of zein, and entrapment of 40 wt.% of gluten, respectively. Surface characterization of BC prepared with zein and gluten under the optimal conditions confirmed that the cereal proteins were incorporated into the BC nanostructures via solvent exchange and/or entrapment and the original chemical and crystal structures of BC were not significantly changed. Limiting oxygen index (LOI) analysis confirmed that cereal proteins improved the flame retardancy of BC. In particular, the LOI of BC entrapped with gluten was 50%, which was better than that of cowhide leather. Char morphology analysis confirmed that the as-produced BCs with cereal proteins exhibited condensed-phase flame-retardant mechanism by forming intumescent chars. Analysis of the mechanical properties confirmed that compared with cowhide leather, as-produced BCs with cereal proteins possessed high tensile strength and dimensional stability, making them suitable leather substitutes.
Time to recovery from severe community-acquired pneumonia and its predictors among 6 to 59 months of age children admitted to South Wollo zone public hospitals, North East Ethiopia: a prospective follow-up study
Authors: Teferi Mekonnen , Addisu Elsabeth , Wodajo Shambel , Muche Amare , Endawekie Abel , Adane Bezawit , Dessie Tilahun , Kebede Natnael
Published: August 2024

Introduction

Ethiopia is one of those countries with higher burden of community acquired pneumonia among its people, under five children are the members of society that are highly affected by pneumonia particularly Severe Community Acquired Pneumonia. However, there are limited studies on time to recovery and its predictors in under-five children and most of them are retrospective which fails to address important variables that affect the time to recovery. Therefore, the aim of this study was to estimate the median time to recovery and its predictors among under five children admitted to South Wollo zone public hospitals, North East Ethiopia.

Methods

An institution-based prospective cohort study was conducted from March 10 to May 10, 2021, with 270 study subjects. A systematic random sampling technique was used. Data was collected by interview and chart review. The data were entered and analyzed using Epi Data version 3.1 and STATA version 14.0, respectively. Kaplan-Meier and Cox regression models were used to test the time and predictors of recovery from severe community-acquired pneumonia.

Results

The overall incidence of recovery rate (95% confidence interval) from Severe Community-Acquired Pneumonia was 20.45(17.84–23.46) per 100 person days observation with median (IQR) time to recovery of [3, 5] days. The predictors of time to recovery from Severe Community-Acquired Pneumonia were having comorbidities on admission [AHR = 0.49 (95%CI: 0.32,0.75)], reaching hospitals after 5 days of onset of symptoms [AHR = 0.35 (95%CI: 0.20,0.60)], having Middle Upper Arm Circumference < = 12.5 cm [AHR = 0.21 (95%CI: 0.12,0.37)], the presence of smoker in the house [AHR = 0.21 (95%CI: 0.10,0.42)] and being not fully immunized for age [AHR = 0.35 (95%CI: 0.24,0.53)].

Conclusion and recommendations

Generally the recovery time of children with Severe Community Acquired Pneumonia in the study area was within the recommended national standards. Due attention should be given to children with the identified predictors while treating them.
“But how true that is, I do not know”: the influence of written sources on the medicinal use of fungi across the western borderlands of the former Soviet Union
Authors: Prakofjewa Julia , Sartori Matteo , Kalle Raivo , Łuczaj Łukasz , Karbarz Małgorzata , Mattalia Giulia , Šarka Povilas , Prūse Baiba , Stryamets Nataliya , Anegg Martin , Kuznetsova Natalia , Kolosova Valeria , Belichenko Olga , Aziz Muhammad Abdul , Pieroni Andrea , Sõukand Renata
Published: August 2024

Fungi have been used for medicinal purposes for many centuries. This study, based on 35 historical written sources and 581 in-depth semi-structured interviews from eight countries in the western borderlands of the former Soviet Union, investigates the medicinal use of fungi by local communities. We compared the taxa and uses obtained from fieldwork and historical sources with works that advocated fungi use within Soviet herbals, representing the centralised medical system. During fieldwork, we identified eight locally used fungi and one lichen. The highest numbers of medicinal uses were documented in Russia, Estonia and Ukraine. Studies published before the Soviet era listed 21 fungal taxa and one lichen species used in the study region. However, only six of these taxa were mentioned as used by people in our field studies (Amanitamuscaria, Boletusedulis, Lycoperdon, Morchella, Phallusimpudicus and Cetrariaislandica). Notably, these same six taxa were consistently endorsed in Soviet herbals. Of the remaining three taxa recorded in the fieldwork, none were mentioned in historical written sources. However, they were promoted either in Soviet herbals (Inonotusobliquus, Kombucha) or later popular publications (Cantharelluscibarius). This highlights the significant influence of written sources on the use of fungi for medicinal purposes within the studied local communities.
Insights Into the Patient Experience of Hormone Therapy for Early Breast Cancer Treatment Using Patient Forum Discussions and Natural Language Processing
Authors: Sreenivasan Sameet , Fang Chao , Flood Emuella M. , Markuzon Natasha , Sze Jasmine Y.Y.
Published: August 2024

PURPOSE

Understanding the real-world experience of patients with early breast cancer (eBC) is imperative for optimizing outcomes and evolving patient care. However, there is a lack of patient-level data, hindering clinical development. This social listening study was performed to understand patient insights into symptoms and impacts of hormone therapy (HT) for eBC using posts from patient forums on breastcancer.org to inform future clinical research.

METHODS

Natural language processing (NLP) and machine learning techniques were used to identify themes related to eBC from a sample of 500,000 posts. After relevant data selection, 362,074 eBC posts were retained for further analysis of symptoms and impacts related to HT, as well as insights into symptom severity, pain locations, and symptom management using exercise and yoga.

RESULTS

Overall, 32 symptoms and nine impacts had significant associations with ≥one HT. Hot flush (relative risk [RR], 6.70 [95% CI, 3.36 to 13.36]), arthralgia (RR, 6.67 [95% CI, 3.53 to 12.59]), weight increased (RR, 4.83 [95% CI, 3.20 to 7.28]), mood swings (RR, 7.36 [95% CI, 5.75 to 9.42]), insomnia (RR, 4.76 [95% CI, 3.14 to 7.22]), and depression (RR, 3.05 [95% CI, 1.71 to 5.44]) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥one HT despite their low overall prevalence in eBC posts.

CONCLUSION

The social listening approach allowed the identification of real-world insights from posts specific to eBC HT from a large-scale online breast cancer forum that captured experiences from a uniquely diverse group of patients. Using NLP has a potential to scale analysis of patient feedback and reveal actionable insights into patient experiences of treatment that can inform the development of future therapies and improve the care of patients with eBC.
Preliminary results from a phase I expansion study of ZG005, a bispecific antibody targeting TIGIT and PD-1, as monotherapy in patients with advanced solid tumors.
Authors: Qin Shukui , Cheng Ying , Wang Qiming , Cheng Shuxia , Chai Xiaoli , Wu Lihua , Yu Yan , Shi Jianhua , Li Xiumin , Fan Lianlian , Xia Jin , Huang Yisheng , Ji Yinghua , Zhuang Zhixiang , Yang Lei , Jiang Ou , Zheng Qinhong , Liao Sihai , Yi Shanyong , Ye Huangyang
Published: August 2024

2611

Background: ZG005, a PD-1 and TIGIT dual-specific antibody, is a promising immunotherapy for tumors as blocking these two pathways could synergistically activate T cells and enhance the anti-tumor activity of NK cells. Partial results from the dose-escalation stage of this first-in-human (FIH) study were revealed at ASCO 2023, and here we present the preliminary results from the dose-expansion stage. Methods: After a dose-escalation stage, patients (subjects) with solid advanced tumors were enrolled into this dose-expansion stage. Subjects in each cohort were randomized 1:1 to receive ZG005 treatment of either RP2D from the dose-escalation stage (10 mg/kg Q3W or 20 mg/kg Q3W) by intravenous infusion. Efficacy was assessed primarily according to RECIST v1.1. Results: The dose-escalation stage was completed with 32 subjects enrolled and the dose-expansion stage is currently ongoing. As of December 25, 2023, a total of 68 subjects were treated with ZG005 as monotherapy, including 33 males (median age 60) and 35 females (median age 58), wherein 33 had received PD-1/PD-L1 inhibitors before enrollment. Three subjects with either pancreatic neuroendocrine cancer, intrahepatic cholangiocarcinoma, or cervical cancer were treated for more than 20 cycles. The subject with cervical cancer maintained PR status for more than 35 weeks. A total of 1 CR, 6 PR, and 28 SD cases were reported from the 57 efficacy evaluable subjects, among them 1 CR, 5 PRs, and 8 SDs from the 17 subjects with cervical cancer. A total of 43 TRAEs (43/68, 63.2%) were reported, of which 6 were ≥ grade 3, including 2 liver function abnormalities, 1 elevated γ-glutamyl- transferase, 1 unknown death, 1 hypertriglyceridemia and lipase elevation, and 1 elevation in both aspartate aminotransferase and blood bilirubin. SAEs occurred in 19 subjects, 3 events were related to ZG005, including 2 liver function abnormalities (1 was a DLT event), and 1 unknown death. The death event occurred in one female, who received only one dose of ZG005, and the cause of her death was most likely due to poor underlying condition. The Cmax and AUC increased approximately in dose proportion. Conclusions: ZG005 has demonstrated a tolerable safety profile and encouraging anti-tumor activity during the FIH study. Expansion cohorts in specific advanced solid tumors are underway to warrant further development. Clinical trial information: CTR20220021.
A phase II clinical trial of metformin combined with FOLFIRI plus bevacizumab as second-line therapy in patients with RAS-mutant metastatic colorectal cancer.
Authors: He Wen-zhuo , Jiang Chang , Yi Jiahong , Xue Ju , Yin Zhao-feng , Dong Wen-jing , Xia Liang-Ping
Published: August 2024

3534

Background: Metastatic colorectal cancer (mCRC) patients with RAS mutations are confronted with limited novel targeted therapy. We previously reported that KRAS mutation mediated MATE1 down-regulation sensitizes colorectal cancer cells to metformin. Based on our preclinical research, we designed a study to explore whether metformin combined with FOLFIRI plus bevacizumab would improve efficacy in RAS mutant mCRC. Methods: This single-arm, multicenter trial (ChiCTR2000037943) recruited patients with RAS mutant mCRC that had failed to first-line bevacizumab plus an oxaliplatin-based regimen of systemic therapies. Patients received metformin 1000mg PO twice daily on day 1-14, plus irinotecan 180 mg/m² IV, calcium folinate 400 mg/m² IV, fluorouracil 400 mg/m² IV, and a 46-h CIV of fluorouracil 2400 mg/m², and bevacizumab 5 mg/kg IV, repeated every 14 days. We used Simon's two-stage design. The primary endpoint was objective response rate (ORR). The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: One hundred sixteen patients were recruited between July 2020 and March 2023. KRAS codon 12 mutations were present in 81 cases (69.8%), codon 13 mutations in 17 cases (14.7%), codon 61 mutations in 6 cases (5.2%), and codon 146 mutations in 3 cases (2.6%). For the 81 patients with KRAS codon 12 mutation, 42 were with G12D (51.9%), 21 with G12V (25.9%), 7 with G12A (8.6%), and 6 with G12C (7.4%) mutation. The ORR was 21.6% (25/116), and DCR was 76.7% (89/116). The median PFS was 8.0 months, and patients without liver metastasis had longer PFS than those with liver metastasis (9.5 months vs. 5.6 months, P < 0.001). For the 45 patients without liver metastasis, the administration of metformin combined with FOLFIRI plus bevacizumab as second-line therapy resulted in significantly longer PFS than the first-line bevacizumab plus an oxaliplatin-based regimen (9.5 months vs. 7.9 months, P = 0.037). The median OS was not reached. The most common treatment-emergent adverse events (TEAEs) were neutropenia (73.7%), nausea (56.9%), anemia (54.3%) and diarrhea (49.1%). Grade 3 and above TEAEs occurred in 52 (44.8%) patients. No treatment-related mortality occurred. Conclusions: Metformin combined with FOLFIRI and bevacizumab had promising efficacy and tolerable toxicity in RAS mutant mCRC patients as second-line therapy. Further study in phase 3 trials is warranted. Clinical trial information: ChiCTR2000037943.
Efficacy and safety of combination therapy with binimetinib, encorafenib, and cetuximab for BRAF non-V600E mutated metastatic colorectal cancer: Results from a phase 2 BIG BANG trial (EPOC1703).
Authors: Kotani Daisuke , Bando Hideaki , Taniguchi Hiroya , Masuishi Toshiki , Esaki Taito , Sunakawa Yu , Komatsu Yoshito , Shinozaki Eiji , Satoh Taroh , Nishina Tomohiro , Nakamura Yoshiaki , Mikamoto Yuichi , Wakabayashi Masashi , Sato Akihiro , Nomura Shogo , Ebi Hiromichi , Yoshino Takayuki
Published: August 2024

3585

Background: BRAF mutations which are found in 8-12% of metastatic colorectal cancer (mCRC) can be classified into three groups; Class 1 and 2 tumors do not respond to anti-EGFR antibody therapy because of the RAS independent activity, while previous studies suggested potential anti-tumor activity of anti-EGFR antibody for class 3 tumor. Combination therapy with binimetinib, encorafenib, and cetuximab showed the substantial efficacy for BRAF V600E mutated mCRC in the BEACON CRC trial, however, the clinical activity of these triplet therapy for BRAF non-V600E mutated mCRC is unknown. Here, we conducted a multicenter phase 2 trial to assess the efficacy and safety of combination therapy with binimetinib, encorafenib, and cetuximab in patients with BRAF non-V600E mutated mCRC. Methods: We enrolled patients with RAS wild-type and BRAF non-V600E mutated mCRC, refractory or intolerant to at least one fluoropyrimidine-based chemotherapy, and no prior history of anti-EGFR antibody (primary analysis cohort) or refractory to prior anti-EGFR antibody (anti-EGFR antibody refractory cohort). Enrolled patients receive binimetinib (45 mg BID), encorafenib (300 mg QD), and cetuximab (initially 400 mg/m2 and subsequently 250 mg/m2, weekly) until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed confirmed objective response rate (ORR) in the primary analysis cohort with sample size of 21 patients. Results: Between May 2018 and March 2023, 12 and 20 patients were enrolled in the primary analysis cohort and the anti-EGFR antibody refractory cohort, respectively (same order in the following abstract). 7 and 19 patients had a history of ≥ 2 lines of previous chemotherapy, respectively. The most frequent mutation overall was BRAF D594G (n=14, 43.8%). There were each 2 responders in both cohorts, resulting in 16.7% (95%CI, 2.1-48.4%) and 10.0% (95%CI, 1.2-31.7%) of confirmed ORR, respectively. Among 7 patients harboring class 1 or 2 tumors in both cohorts combined, there were 2 responders (ORR 28.6%). Median progression-free survival was 3.3 months and 3.0 months, respectively. Grade 3 or higher adverse events occurred in 4 and 10 patients, respectively, and no new safety signals were identified. Conclusions: The combination therapy with binimetinib, encorafenib, and cetuximab showed modest efficacy for BRAF non-V600E mutated mCRC, with a manageable safety profile, although there was not enough statistical power due to slow accrual. Circulating-tumor DNA analyses at the timepoint of before and after treatment are ongoing. Clinical trial information: UMIN000031857. [Table: see text]
68Ga-FAPI-04 positron emission tomography/computed tomography (PET/CT) for detecting occult peritoneal metastasisin locally advanced gastric cancer: A single-center prospective cohort study.
Authors: Hu Qiancheng , Gou Hongfeng , Hu Jiankun
Published: August 2024

4081

Background: Occult peritoneal metastasis (OPM) is a common finding in patients diagnosed with advanced gastric cancer. Preoperative diagnosis of OPM is crucial for developing treatment strategies and for evaluating the prognosis of patients with locally advanced gastric cancer. To evaluate the accuracy of 68Ga-FAPI-04 PET/CT in diagnosing OPM in locally advanced gastric cancer. Methods: This was a prospective, observational, single-center, single-blind, cohort study. Patients with histologically proven locally advanced gastric or gastroesophageal junction adenocarcinoma on initial staging evaluation were recruited. Laparoscopic staging and cytological analysis of peritoneal washing served as reference standards for the final diagnosis. The primary outcome was the proportion of participants changing treatment strategy from curative to palliative treatment. Results: A total of 49 patients were recruited between November 2022 and July 2023 .Nine of the 49 patients were diagnosed with OPM following 68Ga-FAPI-04 PET/CT examinations. A total of 18.4% (n=9) of patients with locally advanced disease on initial staging evaluation by contrast-enhanced CT were upstaged to stage IV for peritoneal metastasis on 68Ga-FAPI-04 PET/CT. The sensitivity of 68Ga-FAPI-04 PET/CT in detecting OPM was 85.7%, and the specificity was 92.3%. The overall diagnostic accuracy of 68Ga-FAPI-04 PET/CT was 91.8%. Based on ROC curve analysis, the area under the curve (AUC) was 0.893 (95% CI: 0.734–1). Conclusions: The findings of this study suggest a significantly additional value of 68Ga-FAPI-04 PET/CT in detecting OPM. Thus, it would be useful to include 68Ga-FAPI-04 PET/CT in the guidelines for staging locally advanced gastric cancer, instead of laparoscopic staging. Clinical trial information: ChiCTR2300067591.
Hepatic artery infusion chemotherapy (HAIC) combined with tislelizumab and lenvatinib for initial unresectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus: A prospective, single-arm phase II trial.
Authors: Pan Long , Sun Ruirui , He Qiang , Zhou Yin , Li Jiachu , Gou Yang , Wu Chenrui , Fu Zixuan , Zhao Yaowu , He Qin , Huang Ping
Published: August 2024

4103

Background: The combination of immune checkpoint blockade and multikinase inhibitor has been proven to improve clinical outcomes of advanced HCC. Hepatic arterial infusion chemotherapy is an intra-arterial procedure that has been widely used in Asia, with high response rate. The aim of this trial was to evaluate the efficacy and safety of HAIC combined with tislelizumab and lenvatinib for initial unresectable HCC with portal vein tumor thrombus (PVTT). Methods: This is a prospective, single-arm phase II study. Patients with histologically or cytologically diagnosed or clinically confirmed hepatocellular carcinoma and accompanied by PVTT, no previous systemic treatment were eligible for inclusion. Patients received HAIC(FOLOFOX), combined with intravenous tislelizumab (200mg, q3w) and lenvatinib (8/12mg, qd) for six cycles, followed by maintenance therapy with tislelizumab and lenvatinib until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST 1.1 and mRECIST. Results: Between Sep, 2021 to Nov, 2023, a total of 29 eligible patients were enrolled and evaluable for efficacy analyses: median age 54 years (M/F:25/4; CNLC stage IIIa/IIIb: 24/ 5). Portal vein tumor thrombus PVTT Ⅰ-Ⅱ/PVTT Ⅲ-Ⅳ:19/10. An average of 4.35 times of HAIC were underwent in these patients. With a median follow-up of 11 months (interquartile range [IQR] 7.5-21.5), the confirmed ORR was 68.97% (95%CI 49.19-84.72)and 58.62%(95%CI 38.94-76.48)per mRECIST and RECIST v1.1, respectively. The disease control rate (DCR) according to mRECIST and RECIST v1.1 were both 93.10% (95%CI 77.23-99.15). Median progression-free survival (PFS) was 15 months (95%CI 10-22). Median overall survival (OS) was not reached. 7(24.1%) patients became eligible for surgical resection. 1 of them received surgical resection and was confirmed as pathological CR; 6 of them refused surgical treatment and received tislelizumab and lenvatinib treatment continuously. 27(93.1%) patients had mild treatment related adverse events (TRAEs) (grade 0-2). Common TRAEs included hypoproteinemia (93.10%), abdominal pain (72.41%), nausea (68.97%) and leukopenia (65.52%). There were no deaths due to TRAEs. Conclusions: HAIC (FOLOFOX) combined with tislelizumab and lenvatinib afforded promising efficacy and safety in tumor control in patients with advanced HCC with PVTT in short-term observation and an eligible surgical conversion rate was observed. Clinical trial information: CHiCTR2100051717.
Overall survival outcomes of phase II GECCOR-GB trial, a multicentre trial of adjuvant adjuvant gemcitabine plus cisplatin (GC) and capecitabine with concurrent capecitabine radiotherapy (Cape-RT) for operated gallbladder cancer (GBC).
Authors: BHARGAVA PRABHAT GHANSHYAM , Patkar Shraddha , Ostwal Vikas S. , Engineer Reena , Parulekar Manali , Mandavkar Sarika , Srinivas Sujay , KRISHNATRY RAHUL , Gudi Shivakumar , Kapoor Akhil , Pandey Durgatosh , Patel Swapnil , Shinghal Abhishek , Goel Alok , Dora Tapas Kumar , Chaudhary Debashish , Ankathi Suman Kumar , Goel Mahesh , Ramaswamy Anant
Published: August 2024

4124

Background: The optimal adjuvant treatment for gallbladder cancer (GBC) after surgery remains unclear. We previously reported 1 year of disease-free survival (DFS) of adjuvant gemcitabine plus cisplatin (GC) or capecitabine with concurrent capecitabine radiotherapy (Cape-RT). Here, we present the secondary endpoint of the 3-year outcomes of the GECCOR-GB study. Methods: We conducted a multicenter, open-label, non-comparative randomized phase II trial of adjuvant GC or Cape-RT in patients with resected GBC. Patients were randomized 1:1 to receive either GC (gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 of a 21-day cycle for 6 cycles) or Cape-RT arm {Capecitabine 1000 mg/m2 BD on days 1–14, q 3 weeks for 2-4 cycles followed by chemoradiation (RT: 45 Gy over 25 fractions concurrent with capecitabine: 825 mg/m2 BD) followed by 2-4 cycles of capecitabine for a total of 6 cycles}. The primary endpoint was DFS, and the secondary endpoints were overall survival (OS), safety, and treatment completion rates. Results: We enrolled 90 patients at 3 centers in India between May 2019 and February 2022 and randomly assigned 45 patients to each arm. In the GC arm, the median age of patients was 56 (33–72) years, and 23 (51%) patients were in stage II. While in the cape-RT arm, the median age was 55 (26–69) years, with 27 (60%) patients in stage II. The 3-year DFS was 54.3% in the GC arm and 70.7% in the Cape-RT arm, respectively. The 3-year OS was 75% in the GC arm and 73% in the Cape-RT arm, respectively. The 3-year OS in stage II patients (n = 23) in the GC arm was 91.3%, while in the cape-RT arm (n = 27), it was 91.9%. Median OS in stage III patients (n = 22) was 39.1 (95% CI, 33.4–44.6) months in the GC arm, while in the cape-RT (n = 18), it was 23.2 (95% CI, 7.0–39.4) months. Conclusions: Adjuvant GC arm patients, especially those in stage III, had encouraging OS at 3 years, while both GC and adjuvant Cape-RT arms had excellent 3-year OS, reaching more than 90% in patients with stage II-operated GBC. Further studies are needed to compare and validate these findings for GBC patients. GECCOR-GBwas led by Tata Memorial Hospital (TMC), Mumbai. Clinical trial information: CTRI/2019/05/019323.