This research paper presents a study protocol for an exploratory clinical trial evaluating the safety and potential efficacy of autologous peripheral blood mononuclear cell (PBMNC)-loaded injectable cell scaffold (ICS-001) for angiogenic therapy in chronic limb-threatening ischaemia (CLTI). CLTI, the advanced stage of peripheral artery disease, presents significant therapeutic challenges.

Angiogenic therapy using ICS-001 with PBMNCs—a novel approach designed to enhance local cell retention and promote neovascularisation—will be explored. The study will address the pathophysiology of CLTI, the limitations of current treatments and the rationale for cell-based therapies, alongside the clinical trial design for evaluating the safety and efficacy of ICS-001. We hypothesise that ICS-001 will improve ulcer healing and reduce ischaemic rest pain in patients with CLTI. This paper outlines the methodology, including patient selection, CD34⁺ cell mobilisation, scaffold preparation, injection protocols, clinical assessments, data collection and safety monitoring. The anticipated results, discussion and conclusion will offer insight into the clinical significance and potential impact of ICS-001 as a pioneering angiogenic therapy for CLTI.

The institutional review boards of all participating hospitals approved this study protocol (latest version V.6.0, 5 June 2025). Final data will be made publicly available. A report detailing the study results will be submitted for publication in an appropriate peer-reviewed journal.

Data are available on reasonable request. Technical appendix, statistical code is available by contacting the corresponding author. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) licence, which permits others to distribute, remix, adapt, build on this work non-commercially, and licence their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

jRCT2052230115, Japan Registry of Clinical Trials.

Presenteeism, defined as reduced work efficiency due to health issues despite attending work, accounts for a substantial proportion of labour productivity loss. Although pain significantly impacts presenteeism, the relationship between pain and presenteeism remains poorly understood due to the multifaceted nature of pain, encompassing psychosocial factors and daily functioning. This study aimed to identify which of these factors are significantly associated with presenteeism among employees.

Cross-sectional study using self-administered questionnaires and generalised additive model analysis.

Multiple workplaces (including a university and hospitals) in Japan.

Employed individuals (n=212, age range: 20–65 years; 59 males and 153 females) participated. They were recruited through workplace bulletin boards, email announcements and direct invitations. Participants with and without chronic pain were included.

Participants completed self-report measures, including the Health and Work Performance Questionnaire (HPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Pain Catastrophising Scale (PCS), Beck Depression Inventory-second edition (BDI-II), State-Trait Anxiety Inventory (STAI) and WHO Disability Assessment Schedule 2.0 (WHODAS 2.0).

The results indicated that absolute HPQ was significantly associated with BDI-II scores (F=4.51, p=0.035). On the other hand, relative HPQ was influenced by SF-MPQ (F=3.76, p=0.005), PCS (F=4.16, p=0.014), STAI (F=5.62, p=0.019) and limited daily activities (F=13.25, p=0.00035).

These findings suggest that presenteeism is multifactorial, with pain, psychosocial factors and daily functioning playing critical roles. Moreover, the impact of depression on presenteeism differs from that of pain and anxiety. Therefore, tailored intervention approaches may be required for each factor, ultimately improving workplace productivity.

This study was preregistered at UMIN-CTR (UMIN000054797).