Safety Activity Research Articles

Running women or women runners: Does identity salience affect intention to exercise outside and feelings of safety?

AbstractSafety concerns for women are prevalent and influence their likelihood to exercise outside. While some women modify their exercise behaviour due to safety concerns, others exercise outside more freely. In this paper, two experiments are reported with women runners to examine whether making their identity as a runner or a woman salient changed their self‐reported likelihood of exercising outside, sense of safety and personal safety anxiety. While study 1 (n = 153) found no significant experimental effect, it revealed a trend: women whose runner identity was made salient were more likely to self‐report their willingness to exercise outside than those in the gender identity condition. Study 2 (n = 236) was conducted to examine this trend further. The second study employed a larger sample size and a more robust manipulation of social identity salience. A significant effect of the experimental condition on women's sense of safety was observed. Specifically, women in the runner identity salience condition had significantly greater feelings of safety than women in the gender identity salience condition. A similar trend emerged for self‐reported likelihood to exercise outside. These findings corroborate prior research on the impact of identity salience on intention to engage in health behaviours. They contribute to the existing body of literature on the intricate interplay between women's physical activity intentions and safety concerns. Furthermore, these findings could aid in the development of interventions to increase women's physical activity levels. Please refer to the Supplementary Material section to find this article's Community and Social Impact Statement.

Camrelizumab plus apatinib and SOX as first-line treatment in patients with alpha-fetoprotein–producing gastric or gastroesophageal junction adenocarcinoma: A single-arm, multi-center, phase 2 trial.

351 Background: Patients (pts) with AFP-producing G/GEJ adenocarcinoma generally respond poorly to first-line standard chemotherapy. We aimed to assess the efficacy and safety of first-line camrelizumab plus apatinib given concurrently with chemotherapy, followed by camrelizumab plus apatinib in AFP-producing G/GEJ adenocarcinoma pts. Methods: In this open-label, single-arm, multi-center, phase 2 trial (NCT04609176), pts with aged ≥18 years, clinical stage III-IV, unresectable/recurrent or metastatic G/GEJ adenocarcinoma with no prior systemic therapy, serum AFP > 2×ULN or AFP positive by the IHC staining method were enrolled. Pts received 4 cycles of standard S-1 plus oxaliplatin (SOX) and camrelizumab (200mg, iv, d1, q3w) plus apatinib (250mg, po, qd). Pts without disease progression then continued to receive camrelizumab plus apatinib for up to 24 months, or until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1; secondary endpoints included the duration of response (DoR), disease control rate (DCR), progression free survival (PFS), overall survival (OS) and safety. Results: A total of 36 pts were enrolled and received treatment between Dec 4, 2020 and Aug 4, 2023. 35 pts were evaluable for tumor response. Median age was 63 years (range: 28, 78), with 30 pts (83.3%) were male. 13 pts (36.1%) presented with GEJ. 34 pts (94.5%) were diagnosed with stage IV. 20 pts (55.6%) had distant lymph node involvement, 18 (50.0%) had liver metastasis, 8 (22.2%) had peritoneal metastasis, and 2 (5.6%) had lung metastasis. Median serum AFP level was 739.8 ng/ml (range: 77.7, 321847.0). At data cut-off (Sep 1, 2023), the median follow-up duration was 6.4 months (range: 0.7, 27.0). Efficacy was assessed in the FAS population (n = 36). 2 pts showed complete response (CR, all confirmed), 22 had partial response (PR, 18 confirmed) and 7 had stable disease (SD). In consequent, the unconfirmed ORR was 66.7% (24/36) and DCR was 86.1% (31/36), with a confirmed ORR of 55.6% (20/36). The median PFS and OS were still immature. However, the estimated 12-month PFS rate was 42.1%. Any grade treatment-related adverse events (TRAEs) occurred in 33 pts (91.7%) and grade ≥ 3 in 13 (36.1%) pts. The most common grade ≥ 3 TRAEs were decreased neutrophil count (13.9%), hypertension (8.3%) and diarrhea (5.6%). 16 pts (44.4%) experienced immune-related adverse events (irAEs) of any grade. No new safety signals were reported. Conclusions: In AFP-producing G/GEJ adenocarcinoma pts who had not previously received systemic therapy, camrelizumab plus apatinib with SOX followed by camrelizumab plus apatinib showed promising antitumor activity and acceptable safety profile. Clinical trial information: NCT04609176 .

Durable efficacy of selpercatinib in patients with RET fusion+ solid tumors, with a focus on GI tumors: LIBRETTO-001.

746 Background: Selpercatinib, a first-in-class highly selective and potent RET kinase inhibitor with CNS activity, is approved in multiple countries for the treatment of RET-activated cancers. This update includes more patients (pts, n=52) and 16 months (mo) longer follow-up (data cut-off: 13Jan2023) in RET fusion+ solid tumors other than lung/thyroid with a focus on GI histologies. Methods: The phase 1/2 LIBRETTO-001 trial (NCT03157128) enrolled pts with locally advanced/metastatic RET fusion+ solid tumors. 51/52 pts received the recommended dose of 160 mg orally. The efficacy analysis set consisted of pts enrolled ≥6 months prior to the cut-off date. Primary endpoint was objective response rate (ORR) by independent review committee (IRC). Secondary endpoints included ORR by investigator (INV), duration of response (DoR), progression-free survival (PFS), and safety. Results: Of the 52 pts with RET-activated solid tumors other than lung or thyroid, 51.9% were female with a median age of 54.0 years. The majority (31/52) of patients had GI RET fusion+ tumor types, with pancreatic (N=13) and colorectal (N=13) as the most common (Table). 47 pts received prior systemic therapy (median prior lines: 2, range 0-9); 28.8% received ≥3 lines. In 52 efficacy-evaluable pts, confirmed ORR by IRC was 44.2% (23/52, 95% CI: 30.5, 58.7). ORR by IRC for pts with pancreatic tumors was 53.8% and for colorectal tumors was 30.8%. Clinical benefit (complete response + partial response + stable disease ≥16 weeks) was observed in 67.3% (35/52) of pts. Median DoR was 37.2 mo (95% CI: 13.3, NE) for overall pts (Table). No new safety signals were identified compared to previous reports. 4 grade 5 AEs were observed (unrelated to treatment by INV), and 2 pts discontinued due to treatment-related AEs per INV. Conclusions: Selpercatinib continued to demonstrate durable antitumor activity and tolerable safety in pts with RET fusion+ cancers across multiple tumor types and fusion partners, including difficult-to-treat GI cancers with poor results in standard-of-care options, such as pancreatic and colorectal. These results emphasize the importance of comprehensive genomic profiling across all tumor types in order to identify actionable oncogenic drivers, including RET fusions. Clinical trial information: NCT03157128 .[Table: see text]

Ezabenlimab (BI 754091) plus modified docetaxel, cisplatin, and 5-fluorouracil (mDCF) followed by chemoradiotherapy (CRT) in patients (pts) with stage III squamous cell anal carcinoma (SCCA): Early efficacy endpoint results from the phase II INTERACT-ION study.

2 Background: CRT is the standard of care for locally advanced SCCA. However, up to 50% of pts experience recurrence/definitive colostomy; there is an unmet need for novel treatment (Tx) options to improve pt outcomes. mDCF is a standard first-line Tx for advanced SCCA, and anti-programmed death protein-1 (PD-1) immunotherapy has been shown to be effective in a subset of chemorefractory SCCA. Preclinical and clinical data support the feasibility and the potential of combining mDCF with anti-PD-1 immunotherapy. Methods: INTERACT-ION (NCT04719988) is an open-label, single-arm study in pts with Tx-naïve Stage III (T4N0 or TxN+) SCCA to evaluate ezabenlimab (anti-PD-1 antibody) plus mDCF as induction therapy, followed by CRT and then maintenance with ezabenlimab. Pts received induction ezabenlimab (240 mg intravenously, every 3 weeks, 3 cycles) plus mDCF (D [40 mg/m2], C [40 mg/m2] on Day 1; F [1200 mg/m2/day for 2 days] every 2 weeks, 4 cycles). If there was no disease progression after 2 months, pts received an additional cycle of ezabenlimab plus 2 cycles of mDCF. Planned early efficacy endpoint analyses were performed after 2 months of Tx. Pts with radiological objective response (OR; RECIST v1.1), pathological (p) complete response (CR)/near CR (<10% viable tumor cells) by repeat biopsy, and molecular CR (undetectable human papillomavirus [HPV] circulating tumor DNA) by liquid biopsy, received involved nodetumor bed CRT with intensity-modulated radiation therapy (IMRT) followed by 7 cycles of ezabenlimab. All other pts received standard IMRT based-CRT. The primary endpoint is the clinical CR rate 10 months after Cycle 1 of ezabenlimab plus mDCF. Results: At analysis cut-off date,43 pts had been enrolled; 37 pts had preliminary early efficacy endpoint evaluation. All but 1 pt (97.3%) received the planned 4 cycles of ezabenlimab plus mDCF prior to evaluation; 1 pt presented with treatment-related capillary leak syndrome after Cycle 1 and died of a lung infection 3 months later. Radiological assessment was performed in 33 pts; 32 (97.0%) had radiological OR including 14 (42.4%) with CR. One HPV- pt had disease progression. Pathological response data were available for 21 pts; 16 (76.2%) had pCR/near pCR. For molecular response, 3 pts were HPV- (excluded). Among 23 HPV+ evaluable pts, 21 (91.3%) had a molecular CR. Two pts had a significant decrease at 2 months (decrease: 14/1 and 54/1); then molecular CR after radiotherapy. No safety signals were identified by an independent safety review committee. Conclusions: Preliminary results from this ongoing Phase II study show promising antitumor activity and manageable safety of ezabenlimab plus mDCF in pts with Tx-naïve, locally advanced SCCA. Further evaluation of this new treatment regimen is warranted. Clinical trial information: NCT04719988 .

Optimizing the Safety and Efficiency of Ngurah Rai Airport Runway, Bali through the Implementation of Stopbar Light

Ngurah Rai Airport is one of the airports with the busiest traffic in Indonesia. Maintaining runway safety and operational efficiency is crucial to the continuous growth of air traffic. Ensuring the safety and efficiency of airport runway operations is paramount in the aviation industry. This study investigates the implementation of Stopbar Lights as a measure to optimize the safety and efficiency of runway activities at Ngurah Rai Airport in Bali. Stopbar Lights serve as a visual aid to pilots, indicating the precise location where they should stop on the runway, contributing to the prevention of runway incursions, and enhancing overall safety protocols. The research method used is a descriptive qualitative method with data collection techniques in the form of observation, unstructured interviews, literature study, and documentation. Results indicate a notable enhancement in runway safety and efficiency following the introduction of Stopbar Lights. The technology not only reduces the risk of runway incursions but also streamlines ground movements, leading to improved operational timelines. Insights from this study provide valuable considerations for airport authorities and aviation professionals seeking to enhance runway management systems.

The role of psychological contract in enhancing safety climate and safety behavior in the construction industry

Purpose This study aims to explore the “psychological contract of safety” (PCS), a key factor in the safety climate (SC), which relies on the behavioral safety actions of workers at construction sites. While numerous factors have been identified in various sectors across different countries, there is a consensus among researchers that there is a dearth of common assessment factors specifically for the Indian construction industry (ICI). Therefore, this study undertakes a systematic review of existing literature to identify the factors that determine PCS in construction and to ascertain the relative importance index (RII) of these variables and their interrelationships using structural equation modelling (SEM). Design/methodology/approach A structured survey was conducted among 420 professionals in the ICI to collect data. This data was then analyzed using descriptive and inferential statistical methods to derive results. Findings The findings of the study indicate that PCS factors have a significant impact on the construction industry (CI). The inferential analysis ranks “Safety System” as the top factor with the highest RII value. The chi-square results highlight two key SC factors that enhance and regulate an organization’s safety performance. The SEM results reveal that SC factors contribute to the improvement of PCS and influence worker safety behavior. Originality/value The outcomes of this study will be beneficial for stakeholders aiming to improve safety at construction sites and enhance safety performance by fulfilling the mutual safety obligations of employers and employees and by improving safety norms, procedures and policy-making. This paper also provides a theoretical framework for scholars to reassess the results in various contexts.

Investigation of the Recent Ice Characteristics in the Bohai Sea in the Winters of 2005–2022 Using Multi-Source Data

The safety of winter activities in the Bohai Sea requires more detailed information on ice characteristics and a more refined ice zone division. In the present study, 1/12°-resolution sea ice characteristic data were obtained based on the NEMO-LIM2 ice–ocean coupling model that assimilated MODIS satellite sea ice observations from the years of 2005 to 2022 to acquire new sea ice hindcasting data. On this basis, the ice period, ice thickness, ice concentration, ice temperature, ice salinity, and design ice thickness for different return periods in the 1/4°-resolution refined zoning were analyzed, which were then compared with the sea ice characteristics in the previous 21-ice-zone standard. The distribution of ice temperature and ice salinity was closely related to the distribution of ice thickness. The results of ice period, ice thickness, and ice concentration, as well as design ice thickness for different return periods, and the comparison with the previous 21-ice-zone standards, showed that the ice condition on the west coast of the Bohai Sea has significantly reduced.

Seasonal rockfall risk analysis in a touristic island: Application to the Tramuntana Range (Mallorca, Spain)

Rockfalls are an ever-present possibility in the mountainous context of the Tramuntana Region (Mallorca, Spain). Recent events have shown the high potential for direct and indirect impact on the safety of people and economic activities, lasting for weeks or even months. In the present study, we start from a probabilistic assessment of the rockfall hazard (spatial propensity and temporal recurrence), based on a detailed historical record of occurrences and rockfall modelling, which is subsequently superimposed on three exposure scenarios and on a social vulnerability assessment. Exposure considers the floating population at three seasons of the year, given the area's high tourist aptitude. Vulnerability considers on the one hand the intrinsic characteristics of individuals and, on the other, the characteristics of the surrounding territory that act to facilitate emergency operations, mitigate the immediate impact and enhance rapid recovery. Due to the characteristics of the island and the spatial distribution of tourism, the results show that the highest density of rockfall trajectories potentially affect areas of high exposure, whose access by emergency services is complex. Not being, in general, the areas of highest individual criticality, those areas have in most situations low support capability installed or nearby.The results constitute a useful tool for emergency and risk management planning in multiple sectors linked to risk governance. Despite the high geographic detail of the analysis, these studies do not replace exposure and vulnerability analysis at the building level, for which the contribution of georeferenced Census data is fundamental.

Experimental study of ion beam interaction with target surface aimed at developing a contactless method for space debris removal by an ion beam

Research and development in the field of space debris (SD) removal technologies is one of the most important and urgent tasks facing all spacefaring nations. By now, a large number of different concepts of removal have already been proposed. One of them is the SD removal by ion beam generated by an ion source installed on board a service spacecraft (SSC). A detailed understanding of the process of ion beam interaction with the SD surface is required to develop an optimal control algorithm for the virtual SSC-SD mated configuration in order to improve this method of SD removal. In addition, when designing the SSC, it is necessary to take into account back flows of the material sputtered from the surface of removed SD by the ion beam, which can contaminate the SSC operating surfaces during the removal maneuver. Within the framework of the presented work, experimental studies were performed to determine the coefficient of accommodation of the ion impulse during the ion beam interaction with the surface of the target simulating the external surface of the removed object. Besides, the flow density of the sputtered target material was experimentally evaluated during its exposure to the ion beam. To do this, we used the radio-frequency ion source (injector) with a beam diameter of 160 mm, which is supposed to be used as an actuating unit on board the SSC designed for transporting the SD objects to the disposal orbit or to the orbits with limited life. When measuring the ion beam accommodation coefficient, the presence of additional force arising on the target due to the flow of sputtered material leaving its surface, and the ion-electron emission process on the target, which could distort the experimental data, were taken into account. To estimate the magnitude of the flows of sputtered target material under the influence of the ion beam, a special experimental design was developed for simulating the presence of a point source of sputtered material. The results obtained in this work will be used for modeling the impact of the ion beam on the surface of real SD objects with complex geometry using the finite element method, for refining the control algorithm of the virtual SSC-SDO mated configuration and for developing proposals on the SSC layout, which should reduce or completely eliminate the negative impact associated with the material sputtering from the SDO surface onto the SSC elements. Successful implementation of the developed method of SDO removal will contribute to improving the safety of space activities for all countries and to the development of the rocket-and-space industry in the Russian Federation, in particular.

Patient safety and the principles of beneficence and non-maleficence

Patient safety actions represent a means to avoid unsafe practices during medical care, establishing rules to instruct health personnel not to be negligent or carry out behaviors that produce or increase the risks inherent to medical practice. On the other hand, bioethics constitutes a discipline to protect the dignity of the patient, against interventions in their entirety to recover, improve or preserve health. In particular, the principles of beneficence and non-maleficence of so-called principalist bioethics are fulfilled with those actions that are aimed at avoiding harm to the patient, through the observance of rules closely related to said principles.

Perceptions of psychosocial safety behaviour (PSB): Qualitative insights on workplace psychosocial safety perceptions & actions within a policing context

Recent behaviour-based approaches to workplace safety have articulated the need to operationalise psychosocial safety behaviour (PSB) as a unique construct within the safety behaviour literature. Research has yet to operationalise PSB according to context-specific psychosocial hazards, nor to identify the individual, interpersonal and systemic enablers and barriers to PSB performance. The present study addresses this gap by identifying the day-to-day psychosocial safety-focused actions and perceptions of psychosocial hazards within a cohort of road policing officers. Semi-structured interviews were conducted in a sample of frontline officers, supervisors, and peer support officers to operationalise context-specific psychosocial safety behaviours. Officer attitudes, control and normative beliefs associated with psychosocial safety behaviour domains were examined according to Ajzen’s (1991) Theory of Planned Behaviour. While examples of both compliance and participatory safety behaviours were cited across all work roles, PSB enactment was more likely characterised as participatory and interpersonally driven in nature. Participant responses consistently referenced the intergenerational effects of PSB role modelling and positive supervisor attitudes towards mental health on PSB awareness and enactment. Positive attitudes towards mental health, perceptions of behavioural control and trust in leadership were nominated as salient factors influencing PSB enactment. The findings of our study extend the existing nomological network of PSB by considering the influences of socio- cognitive and workplace systems influences on psychosocial safety enactment.

Ensuring the safety of business activities in the context of an acute sanctions policy on the part of foreign states (administrative and legal aspect)

The work is devoted to the study of the issue of ensuring the safety of entrepreneurial activity in the context of acute sanctions policies. Why the concept of an acute sanctions policy has been studied. Using historical and legal methods, cases of the application of economic and political sanctions between states in ancient times have been identified. The number of sanctions imposed on the Russian Federation after the events of February 2022 is given. Further, the author's concepts are given in the work: the safety of entrepreneurial activity in the conditions under consideration, ensuring the safety of entrepreneurial activity in a narrow and broad sense. This allows us to take a fresh look at the issue under study, the classification of economic and political sanctions is given. Legal phenomena such as legitimate and non-legitimate sanctions, which are used by various countries, are revealed. By the security of business activity, we mean the following: - the state of the business, formed from a set of constantly performed joint actions of employees of the company, its managers or owners, different in content and direction; - organization and orderly functioning of existing business processes, their protection; - the formation of a planned, progressive movement, goal-oriented development carried out within the framework of a short-term, medium-term and long-term business development strategy; - these actions are aimed at meeting the needs of society in order to systematically generate business profits regardless of internal and external challenges (threats). Ensuring the safety of entrepreneurial activity is impossible without ensuring the security of the state, ensuring the security of the state is impossible without ensuring the safety of entrepreneurial activity.

Влияние изменения климата на формирование границ природных зон на водосборах бассейна реки Асса-Талас

Based long-term climate data, a research database has been created for eight meteorological stations located in various natural-geographical zones of the Assa-Talas river basin; a linear-correlation model of climate indicators has been obtained, allowing to determine the rate of increase in the sums of air temperatures, radiation balance, evaporation from the open water surface or from excessively moistened soil during the biologically active period of the year, annual precipitation, natural moisture coefficient and hydrothermal dryness index, which perform important environment-forming and ecological functions. The results of the study showed that in general, in all natural-geographical zones of the Assa-Talas river basin, the sum of air temperatures, radiation balance, evaporation and hydrothermal dryness index have a positive growth rate, and annual precipitation and the coefficient of natural moisture are negative, contributing to the formation of a positive rate an increase in the deficit of water consumption of agricultural land and a shift in the boundaries of natural zones, which is a signal of the safety of agricultural activities.

Evaluation of quality classification and comfort of the territory of urban ecosystems in terms of “Environmental conditions”

This paper considers an evaluation of environmental conditions on the territory of urban ecosystems. The research was conducted within Jean Monnet Module project 101085133 – EUGREEN, which is co-funded by the European Union. The evaluation of environmental conditions is considered as a constituent part of the integral estimation of many factors affecting the population health. In urban planning, the assessment of climate and environmental conditions is one of the stages of determining the indicator of the quality and safety of life activities of the city population. To assess the quality of life of the population according to the “Environmental conditions” indicators, it is suggested to use bioclimatic characteristics, which are effective indicators of the thermal structure of the environment of human life, especially in conditions of climate change. The purpose of the study is to determine a qualitative assessment of the environmental conditions of various urban areas of Ukraine, as a certain background against which other functions of the city are performed, as well as for their further use to ensure comfortable microclimatic conditions in residential areas.

Comparison of the use of Metyrapone and Osilodrostat for Cushing Disease: A Systemic Review

Introduction: Cushing disease is characterised by excessive production of adrenocorticotropic hormone (ACTH) from the anterior pituitary, which results in increased release of cortisol from the adrenal glands. Nearly 10 to 15 million people per year have been reported to have this rare disease. As of today, there are different therapies available. The chances of recurrence and severe side effects are high. Objectives: To overcome the recurrence and side effects, we compared the drugs metyrapone and osilodrostat (class 11 beta-hydroxylase inhibitors) for their safety, efficacy, and other pharmacological actions before Cushing's disease. Methodology: Nine electronic databases were searched regarding the drugs metyrapone and osilodrostat for the treatment of Cushing's disease using the keywords. A total of 14 case studies were collected, which show different results and conclusions. Results and discussion: Based on the comparison, both drugs exhibited the same mechanism of action, but administering metyrapone showed more severe side effects than osilodrostat. While osilodrostat has greater efficacy, reducing the cortisol level faster, and also, the drug osilodrostat has a prolonged half-life, allowing it to be used only twice daily compared to the drug metyrapone, which requires six times daily dosing. Conclusion: Based on this, we conclude that the drug osilodrostat has a greater advantage over the drug metyrapone and is also the best treatment option for Cushing's disease.

Adherence to Covid-19 vaccination during the pandemic: the influence of fake news.

to understand how fake news has influenced adherence to Covid-19 immunization, from the perspective of health professionals. a qualitative, descriptive-exploratory study was conducted in Campo Grande - MS. Twenty nursing professionals working in vaccine rooms or managing immunobiologicals participated through semi-structured interviews. The interviews were audio-recorded, fully transcribed, and subjected to thematic content analysis. two categories emerged in which the professionals highlighted an increase in vaccine hesitancy among the population, influenced by fake news and denialist actions, which negatively interfered with the population's trust in vaccines and in the professionals administering them. concerns about vaccine safety and denialist actions by authorities and media outlets can contribute to the phenomenon of non-vaccination. The valorization of science, the promotion of educational actions, and raising public awareness about immunization were presented as strategies to increase vaccine coverage.

QL1604 plus paclitaxel-cisplatin/carboplatin in patients with recurrent or metastatic cervical cancer: an open-label, single-arm, phase II trial.

QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46). The median duration of response was 9.6 months (95% confidence interval [CI]=5.5-not estimable). The median progression-free survival was 8.1 months (95% CI=5.7-14.0). Forty-five (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can't tolerate bevacizumab, which needs to be further verified in phase III confirmatory study. Trial RegistrationClinicalTrials.gov Identifier: NCT04864782.

Autologous stem cell transplantation with low-dose cyclophosphamide to improve mucosal healing in adults with refractory Crohn’s disease: the ASTIClite RCT

Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of < 150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm [38 in 13 (100%) patients] than in the usual-care arm [16 in 4 (40%) patients]. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died. Conclusions Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use. Limitations The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive. Future work Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohn’s disease, including those with a stoma or multiple previous resections. Trial registration This trial is registered as ISRCTN17160440 and EudraCT 2017-002545-30. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 3. See the NIHR Funding and Awards website for further award information.

Selective synthesis of pyridazine-fused chromones and 3-pyridazinyl chromones through intermolecular chromone annulation of o-hydroxyphenylenaminones with aryldiazonium salts

A chemodivergent and skeleton-controllable annulation reactions of readily available o-HPEs and aryldiazonium salts was described for the synthesis of highly functionalized pyridazine-fused chromones with high antiviral activity and higher safety.

Camrelizumab combined with apatinib and nanoparticle albumin-bound paclitaxel in lung adenocarcinoma (CAPAP-lung): a single-arm phase II study

Platinum-doublet chemotherapy plus immunotherapy has been the standard of care for the first-line treatment of advanced non-small cell lung cancer lacking actional driver mutations. However, optimization of drug combinations is still needed to find a better balance between therapeutic efficacy and safety in the immunotherapy era. We aimed to investigate the efficacy and safety of platinum-free albumin bound paclitaxel (nab-paclitaxel) combined with camrelizumab and apatinib as first-line treatment for patients with advanced lung adenocarcinoma. In this multicenter open-label, single-arm phase II trial, patients with systemic treatment-naïve advanced lung adenocarcinoma without epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutations received a rational-based combination of camrelizumab (200mg intravenously, day one), apatinib (250mg, q.d., five continuous days per week), and nab-paclitaxel (135mg/m2 intravenously, days one and eight) every three weeks for four to six cycles in China. Patients with controlled disease were maintained with camrelizumab and apatinib. The primary end point was progression-free survival (PFS). This trial is registered with ClinicalTrials.gov (No. NCT04459078). Between August 26, 2020 and May 20, 2022, 64 patients were enrolled. The median PFS was 14.3 (95% CI: 9.9, not reached) months. The confirmed objective response rate was 64.1% (95% CI: 51.1, 75.7). The grade 3-4 hematologic treatment-related adverse events (TRAEs) were decreased neutrophil count (14.1%), decreased white blood cell count (7.8%), and anemia (3.1%). The most common non-hematologic TRAEs of grade 3-4 were increased alanine transaminase (18.8%) and aspartate transaminase (15.6%). No treatment-related death occurred. The quality of life was on average not clinically meaningful worse through treatment cycle14. Nab-paclitaxel plus camrelizumab and apatinib showed clinically meaningful anti-tumor activity and manageable safety, with few hematologic toxicities, and might be a potential treatment option in patients with advanced lung adenocarcinoma lacking EGFR/ALK mutations. Heath Research Foundation of Chinese Society of Clinical Oncology, Hunan Provincial Natural Science Foundation of China, Hunan Cancer Hospital Climb Plan, Sister Institution Network Fund of The University of Texas MD Anderson Cancer Center, The Science and Technology Innovation Program of Hunan Province, and Suzhou Sheng Diya Biomedical Co., Ltd, a subsidiary of Jiangsu Hengrui Pharmaceuticals Co., Ltd. (Shanghai, China).