bluuebunny/crossref_metadata_2025 huggingface dataset:
Paucity of viral infection symptoms in patients with immune-mediated inflammatory diseases
Authors: Yalcin Mutlu Melek , Kleyer Arnd , Kroenke Gerhard , Fagni Filippo , Temiz Selahattin Alp , Meder Christine , Dietrich Peter , Orlemann Till , Mößner Johanna , Schoenau Verena , Bohr Daniela , Schuster Louis , Hartmann Fabian , Minopoulou Ioanna , Leppkes Moritz , Ramming Andreas , Pachowsky Milena L , Schuch Florian , Ronneberger Monika , Kleinert Stefan , Hueber Axel J , Manger Karin , Manger Bernhard , Atreya Raja , Berking Carola , Sticherling Michael , Neurath Markus F , Schett Georg , Simon David , Tascilar Koray
Published: January 2025

Objectives

Although patients with immune-mediated inflammatory diseases (IMID) are thought to be more susceptible to viral infections, it is unclear whether their presentation differs between patients with IMID and healthy controls. This study aimed to investigate the symptom pattern of common viral infections in patients with IMID and compare it with controls without IMIDs.

Design

A cross-sectional study conducted between 1 February and 30 April 2020, using a questionnaire.

Setting

Seven tertiary regional care centers in Germany, which specialised in the care of patients with IMID (namely, in gastroenterology, dermatology, rheumatology and immunology clinical care).

Participants

One thousand nine hundred nine participants completed the survey (757 patients with IMID; 1152 non-IMID controls).

Primary outcome measure

The occurrence of 11 common viral illness symptoms within the preceding 3 months in patients with IMID and non-IMID controls.

Results

Symptom data were clustered, based on number and co-occurrance, into 3 major clusters and 2 subclusters ranked by the average number of symptoms. Patients with inflammatory bowel disease and psoriasis were significantly overrepresented in the lower-frequency subcluster of the polysymptomatic cluster. Patients with rheumatoid arthritis were overrepresented in the lower-frequency subclusters of the intermediate and oligo-/asymptomatic clusters. Controls were over-represented only in the higher-frequency subclusters of each major cluster where none of the IMIDs were over-represented. Spondyloarthritis and other IMIDs were also overrepresented in the low-frequency subcluster, but the results were not significant. Overall, patients with rheumatoid arthritis patients reported fewer symptoms (rate ratio=0.68, 95% CI, 0.59 to 0.80) than non-IMID controls.

Conclusion

Patients with IMID are over-represented in low-frequency subclusters, even among individuals who have reported a broad range of viral infection symptoms. This pattern suggests that the manifestations of viral infections are different between patients with IMID and controls, thus challenging the accurate and early diagnosis of infections.
Effect of different intraoperative blood pressure regulation levels on postoperative myocardial injury in patients undergoing radical mastectomy for breast cancer after receiving neoadjuvant chemotherapy: a study protocol for a randomised controlled trial
Authors: Zhou Zhou , Liu Hongya , Wang Xinxin , Sang Xiaoqiao , Zhang Ying , Liu Yingge , Zhang Xiaobao
Published: January 2025

Introduction

For patients with breast cancer receiving preoperative neoadjuvant chemotherapy with anthracyclines, there is an increased risk of postoperative myocardial injury due to the cardiotoxicity of the chemotherapeutic agents. The optimal intraoperative blood pressure regulation regimen for these patients is unclear. This study is being conducted to determine whether targeting mean arterial pressure (MAP) to 100%–120% of the patient’s baseline blood pressure reduces the incidence of myocardial injury after non-cardiac surgery (MINS) compared with targeting MAP to 80%–100%. MINS is defined as elevated cardiac troponin levels within 30 days after non-cardiac surgery with or without clinical and electrocardiographic signs of cardiac ischaemia.

Methods and analysis

The study is a single-centre, single-blind, prospective randomised controlled trial. It is expected to enrol 166 subjects receiving neoadjuvant chemotherapy with anthracyclines, between the ages of 40 and 75 years, scheduled for radical mastectomy. Participants will be randomised 1:1 to a lower-level group:intraoperative MAP control at 80%–100% of baseline values or a higher-level group:intraoperative MAP control at 100%–120% of baseline values. The primary outcome is defined by the incidence of MINS at 6–8 hours, 24 hours and 48 hours postoperatively. The secondary outcomes are heart-type free fatty acid-binding protein values at 1–2 hours, 6–8 hours and 24 hours postoperatively; the incidence of acute kidney injury within 48 hours postoperatively; the Quality of Recovery-15 score at 24 hours, 48 hours postoperatively; post-anaesthesia care unit length of stay; other postoperative cardiovascular complications; the number of times rescue analgesia and antiemetics are required; the time to first ambulation and length of postoperative hospitalisation.

Ethics and dissemination

This study involves the participation of human subjects and has received approval from the Clinical Trial Ethics Committee at The Affiliated Lianyungang Hospital of Xuzhou Medical University (approval number: KY-20230915001). Study results will be presented at scientific meetings and in scientific publications.

Trial registration number

ChiCTR2300077675.
Effectiveness ofFewer Falls, an online group-based self-management fall prevention programme for people with multiple sclerosis: protocol of a randomised controlled trial
Authors: Tuvemo Johnson Susanna , Flink Maria , Gottberg Kristina , Walker Peterson Elizabeth , Meijer Ulrika , Bylinder Johanna , Kierkegaard Marie , Ytterberg Charlotte
Published: January 2025

Introduction

Fewer Fallsis a manualised self-management fall prevention programme co-developed for and with ambulatory and non-ambulatory people with multiple sclerosis (PwMS). Findings from a feasibility study indicate the necessity of a full-scale randomised controlled trial (RCT).

Methods and analysis

A parallel-group RCT with a mixed methods process evaluation as well as a cost-effectiveness evaluation will be conducted. We aim to recruit 240 PwMS, who will be stratified by ambulation level and randomised 1:1 in blocks of eight to intervention or control. The group-based self-management fall prevention intervention involves eight 2-hour online synchronous sessions (approximately eight participants/group) facilitated by a licensed healthcare professional and home assignments to be completed by participants between sessions. The setting is online, and participants can be located anywhere in Sweden. The control and intervention groups will also receive a brochure on fall risk factors and fall prevention in addition to their standard MS care and rehabilitation. Data collection will be performed at baseline and 3, 6 and 12 months after the start of the intervention. Falls will be monitored via a short message service every week during 1 year from the start of the intervention. The primary outcome is fall frequency (falls/person/year). Secondary outcomes include injurious falls, falls control, fear of falling, falls self-efficacy, activity curtailment, perceived effect of MS, self-rated health and cost-effectiveness.

Ethics and dissemination

Ethical approval has been obtained from the Swedish Ethical Review Authority (registration numbers 2022-06667-01 and 2023-07723-02). The RCT will adhere to the Declaration of Helsinki. Written consent to participate will be obtained from all participants. Study-related information about participants will be stored securely at Karolinska Institutet. The results will be presented in peer-reviewed journals, through the patient organisation Neuro Sweden, at conferences, and in social media.

Trial registration number

ClinicalTrials.gov,NCT05789225.
Relationship between social support and depressive symptoms among internal migrant workers and the mediating role of healthy lifestyle: a cross-sectional study in China
Authors: Ye Beizhu , Chen Yiyang , Ma Mingze , Liu Jingru , Tarimo Clifford Silver , Han Shuo , Xue Kunyu , Zuo Binghe , Wang Yunyun , Song Yalin
Published: January 2025

Objectives

To investigate the association between social support and depressive symptoms among internal migrant workers with a focus on the mediating role of a healthy lifestyle.

Design

Cross-sectional study.

Setting

The research was conducted among internal migrant workers in Henan Province, China, in August 2023.

Participants

Internal migrant workers are defined as individuals residing outside their registered household location (excluding mobility within the municipal district) and participating in various social and economic activities, including employment, entrepreneurship and social services.

Primary outcome measures and analyses

Social support was measured using the Chinese version of the social support rating scale. The severity of depression among the study participants was evaluated using the Patient Health Questionnaire-9. A healthy lifestyle was assessed based on the questionnaire we developed based on the American Medical Association Healthy Lifestyle Scale. Statistical analyses, including logistic regression, Spearman’s correlation and mediation analysis, were deployed to explore the associations between social support, healthy lifestyle and depressive symptoms.

Results

Among 19 326 participants, 21.45% exhibited depressive symptoms, with a higher prevalence observed among males. Social support levels among internal migrant workers were found to be lower than those in the general population, and higher social support was significantly associated with a decreased risk of depressive symptoms (OR=0.102, 95% CI: 0.086 to 0.121). Mediation analysis revealed that a healthy lifestyle partially mediated the relationship between social support and depressive symptoms among internal migrant workers, with a mediation effect of −0.063, accounting for 18.75% of the total effect.

Conclusion

This study provides insights into the complex interplay between social support, healthy lifestyle and depressive symptoms among internal migrant workers in China. Implementing interventions aimed at enhancing social support and promoting healthy lifestyle behaviours can significantly improve the mental health and overall well-being of internal migrant workers.
Adherence to guidelines for natriuretic peptide testing in heart failure: a nationwide survey of healthcare professionals in Vietnam
Authors: Do Doan-Loi , Truong Thanh Huong , Kim Ngoc-Thanh
Published: January 2025

Objectives

This study aimed to determine doctors’ level of adherence to the natriuretic peptide testing guideline and to identify the factors influencing their adherence.

Design

Cross-sectional study.

Setting

Web-based survey.

Participants

Full-time doctors involved in heart failure (HF) treatment in Vietnam.

Primary and secondary outcome measures

Doctors using natriuretic peptide testing for diagnosis, differential diagnosis, treatment assessment and prognosis of patients with HF were classified as adhering to the guidelines. We assessed the practice of natriuretic peptide testing and stratified the doctors based on their professional qualifications. Univariate and multivariate logistic regression analyses were used to estimate the Odds Ratio (ORs) and 95% CIs for associations between guideline adherence and selected covariates.

Results

Over half of the participants adhered to the natriuretic peptide testing guidelines (57.4%). Cardiologists adhered more closely to the guidelines than other professionals; they had approximately four times higher odds of adherence than other doctors (univariate model, OR: 3.88, 95% CI: 2.56 to 5.89, p<0.001; multivariate model, OR: 4.24, 95% CI: 2.64 to 6.82, p<0.001). Cardiologists also had significantly higher rates of using natriuretic peptide testing for diagnosis (93.8% vs 84.1%, p<0.002), differential diagnosis (71.4% vs 53.5%, p<0.001), treatment assessment (87% vs 64.2%, p<0.001) and prognosis (68.2% vs 50.4%, p<0.001) than other professionals. More years of professional experience correlated with higher guideline adherence (<2 years was used as a reference point; >5 to <10 years, OR: 2.59, 95% CI: 1.45 to 4.60, p<0.001; ≥10 years, OR: 2.30, 95% CI: 1.30 to 4.09, p<0.004).

Conclusion

The level of adherence to natriuretic peptide testing guidelines among doctors treating patients with HF varies across Vietnam. Targeted interventions are needed to enhance understanding and proficiency, especially among non-cardiologists and those with limited experience. A dedicated fact sheet focusing on natriuretic peptide testing in HF management, separate from the existing guidelines, could bridge this gap.
Effect of tropical climates on the quality of commonly used antibiotics: the protocol for a systematic review and meta-analysis
Authors: Suleman Sultan , Hasen Gemmechu , Melaku Tsegaye , Belew Sileshi , Thitiri Johnstone , Shangala Jimmy , Obiero Christina W , Ngari Moses , Berkley James A
Published: January 2025

Introduction

Medicine quality can be influenced by environmental factors. In low- and middle-income countries (LMICs) with tropical climates, storage facilities of medicines in healthcare settings and homes may be suboptimal. However, knowledge of the effects of temperature and other climatic and environmental factors on the quality of medicines is limited. A better understanding of the effects of climates may assist in the development of control strategies to help reduce factors contributing to poor-quality medicines. Therefore, this systematic review aims to synthesise data from published studies describing the effects of storage conditions on the quality of antibiotic medicines commonly used in LMICs.

Methods and analysis

We will search literature from databases, including the PubMed, Web of Science, Scopus and Google Scholar, and grey literature between 1987 and 2022. Experimental studies that evaluate the influence of temperature, humidity and sunlight on the quality of antibiotics applicable to Africa and South Asia will be included. Experimental studies that assess naturally occurring and simulated storage conditions and medicines prepared from powder with water and stored in hospitals or at home to be used across several doses will be also included. The key search terms related to the tropical climate, quality and commonly used antibiotics, such as temperature, storage condition, humidity, sunlight and moisture; quality, assay, purity, dissolution, disintegration, hardness, friability, weight variation, weight uniformity, degradation, impurities and stability; and amoxicillin, ceftriaxone, azithromycin, ciprofloxacin, doxycycline, metronidazole, trimethoprim-sulfamethoxazole, erythromycin, ampicillin and gentamicin, respectively, will be connected using the appropriate Boolean operators (OR, AND). The search terms will be used in correspondence with Medical Subject Heading terms by keyword arrangement. The available evidence for the poor quality of commonly used antibiotics is summarised by the type of diagnosis, type of drug and region. Meta-analysis using random effects will be performed using RevMan software to determine the pooled effects of environmental exposures. The degree of heterogeneity will be evaluated by the inverse of variance (I2). Forest plots will be used to present the meta-analysis data.

Ethics and dissemination

Ethical approval is not required as the study is a systematic review. This review will be disseminated through open-access peer-reviewed publication.

PROSPERO registration number

CRD42023432848.
Cardiac arrhythmia assessment with patch electrocardiogram versus insertable cardiac monitor: a cohort study in endurance athletes with atrial fibrillation
Authors: Apelland Turid , Sellevold Andreas Berg , Letnes Jon Magne , Onarheim Sophia , Enger Steve , Tveit Arnljot , Delpire Boris , Claessen Guido , La Gerche Andre , Loennechen Jan Pal , Berge Trygve , Myrstad Marius
Published: January 2025

Objectives

The objective of this study was to assess the quality of ECG recordings and the concordance between the automatic detection of cardiac arrhythmia episodes by a patch ECG and an insertable cardiac monitor.

Design

Prospective cohort study.

Setting and participants

Endurance athletes diagnosed with paroxysmal atrial fibrillation (AF) and no other relevant comorbidities participating in a randomised controlled trial on the effects of training adaption.

Methods

A patch ECG (ECG247 Smart Heart Sensor) was sent to 29 non-elite endurance athletes with clinical paroxysmal AF. ECG247 continuously monitors, detects and categorises cardiac arrhythmias. The participants were simultaneously monitored with an insertable cardiac monitor (Confirm Rx, Abbott). ECG recording quality was assessed by an experienced physician. Training sessions were monitored using sports watches.

Results

Out of 29 invited athletes, 14 athletes (mean age 60.4 years, 2 women) made use of the patch ECG and were monitored for a total of 2987 hours and a median of 14 (range 1–17) days. During this period, the athletes performed a total of 112 training sessions. ECG quality varied between athletes and by type of exercise, with poor quality in 16% and 40% of recordings during cross-country skiing and running, respectively. In two athletes, the patch ECG detected AF episodes that were confirmed with insertable cardiac monitor recordings. One technical artefact was falsely classified as ventricular tachycardia by the ECG247 Smart Heart Sensor system.

Conclusion

Monitoring with patch ECG was feasible in endurance athletes, but ECG recording quality varied between athletes and by type of exercise.

Trial registration

NCT04991337(for the related randomised controlled trial).
Quality improvement on reducing neonatal mortality through intensive Clinical Mentorship Intervention: a case study in Biak Regional Hospital, Papua-Indonesia
Authors: Kresnawati Windhi , Froulina Liza , Syahrizal Bobby Marwal , Sinaga Nurlely Bethesda , Manuama Edit Oktavia , Rohsiswatmo Rinawati , Wandita Setya
Published: January 2025

Background

The neonatal mortality rate in Papua Province of Indonesia is unacceptably high. To address the issue, the Ministry of Health and UNICEF Indonesia initiated a hospital mentoring programme from 2014 to 2016 to improve the quality of care and health workers’ capacity to provide neonatal care. This study aimed to assess the impact of hospital mentoring on neonatal mortality.

Methods

The study was conducted at Biak District Hospital, Indonesia. The neonatal mortality was compared for three periods: preintervention (2011–2013), mentorship intervention phase (2014–2016) and postintervention (2017–2020). The mentoring programme is a combination of a direct-intensive-regular mentoring process and a scholarship programme for paediatricians. In the mentoring process, paediatricians, neonatal nurses and electromedical staff from national hospitals were sent to train the nurses on nursing management for sick neonates, clinical neonatal resuscitation, stabilisation and transportation. The neonatal mortality data were collected from birth registers, medical records, death case review reports and mentoring programme reports.

Results

A significant decrease in the percentage of death cases before 24 hours of hospitalisation and death cases due to asphyxia was observed in the three periods. In the death cases from referrals, a significant decrease from 70% in the intervention period to 39.7% in the postintervention period was observed (p<0.05). The survival rate of neonates with body weights under 1500 g and 1500–2500 g was compared in the intervention and postintervention period, a significant increase from 21% to 58% and 55% to 94% was observed, respectively (p<0.05).

Conclusion

The direct-intensive-regular mentoring intervention programme was found to be effective in reducing neonatal mortality through quality improvement in low-resource district hospitals.
Improving the evaluation of non-accidental trauma across multiple specialties at a single institution
Authors: Kroese Lani , Port Courtney , Hauda William
Published: January 2025

Background

Based on the presenting injury, patients undergoing abuse evaluation may be managed by different specialties. Our local child abuse specialist expressed concern over the variability in evaluation of patients presenting with injuries concerning for non-accidental trauma (NAT). The aim of this quality improvement project was to increase the percentage of patients for whom there is a concern for NAT who receive a guideline-adherent evaluation from 7.7% to 50% in 6 months’ time.

Methods

A committee of physician stakeholders developed criteria for a complete NAT evaluation which were integrated into an order panel with built-in clinical guidance for test selection within our electronic medical record. Data on the completeness of NAT evaluation in paediatric patients 0–18 years of age were collected before and after the order panel release and analysed by admitting service, injury category and equity factors.

Results

This initiative increased the percentage of patients with a guideline-adherent evaluation from a mean of 7.7% to 25% within 6 months’ time. The number of days between patients with complete evaluations decreased from 63 days to 35 days. Order panel utilisation increased to 55%, and the percentage of evaluation opportunities was more complete when the order panel was used (79% vs 92%).

Conclusions

Standardisation of NAT evaluations through creation of an order panel with a clinical decision tool resulted in more guideline-adherent evaluations. The potential reduction of bias in such evaluations remains an area of interest.
Enhancing end-of-life care practices on the medicine units: perspectives from nurses and families
Authors: Reid Julie C , Hoad Neala , Landau Lucinda , Boyle Anne , Hanmiah Rajendar , Cook Deborah J
Published: January 2025

Background

Death is a part of life. While most often a sombre event, opportunities exist to optimise the experience both for the dying patient and their loved ones. This is especially true in institutionalised settings, such as acute care hospitals where cure and recovery tend to be paramount.

Purpose

To understand ways to improve end-of-life (EOL) care from the perspective of frontline nursing staff and patient and family advisors (PFAs).

Methods

We conducted focus groups with frontline nursing staff (n=14) and PFAs (n=5) to understand ways to optimise EOL care. Using a videoconference platform, one researcher used a flexible interview guide while a second researcher took field notes. These focus groups were in follow-up to a comprehensive need assessment survey as part of a programme to enhance EOL care practices on the general internal medicine units at our hospital. We used source data from deidentified audio recordings and researcher field notes.

Results

Five important categories regarding current EOL care practices emerged: communication among key stakeholders, assessment and management of symptoms, engagement of the palliative care team, engagement of the spiritual care team and ongoing tests and interventions at the EOL. We identified challenges specific to each respondent group as well as common challenges from both the professional and public perspectives.

Conclusions

Views elicited from patients, families and nurses in this qualitative study have informed the development of strategies to enhance EOL practices in our hospital that may be useful in othercentres.
Mobile health van as an intervention to provide clinical support and health promotion to street children and marginalised populations in the National Capital Region of Delhi: a mixed-methods evaluation
Authors: Seth Rajeev , Girotra Tanu Girotra , Mohammad Id , Qaiyum Yawar , Taneja Indra , Raman Shanti
Published: January 2025

Background

Urban health challenges, particularly for street and slum-dwelling children and families, have emerged as one of the most significant health concerns in India. While there is little published on effective healthcare delivery to these populations, mobile health vans (MHV) have been proposed as a proactive pathway to providing outreach healthcare. Our aims were to evaluate the impact of Bal Umang Drishya Sanstha (BUDS) MHV in providing health and support services to the urban slum populations in Delhi National Capital Region (NCR), focusing on benefits to children.

Methods

This was a mixed-methods evaluation, using routinely collected data. We collated and reviewed available data recorded by the BUDS staff in their health record system from June 2017 to December 2023. Qualitative data were provided by two recent focus group discussions carried out in the community; one with 18 mothers and another with a mixed group of 12 adults—all had used MHV clinics for children in their families. We chose two typical case studies that were reported to the funding bodies.

Results

Between 2017 and 2023, there were a total of 41 062 clinic visits for children<18 years, with visits increasing steadily and peaking at 8864 in 2023. Just under 10% of encounters were referred to specialist services, 122 children were diagnosed with disability. Health education sessions were provided mainly in group settings, to over 70 000 children. Themes extracted from focus group discussions were enhanced access to healthcare, quality of care, value adds from MHV and suggestions for improvement. Families expressed overwhelming appreciation of BUDS MHV. Case studies illustrated the benefits of facilitated access to tertiary healthcare.

Conclusions

MHV can serve as a valuable source of primary healthcare for street and slum-dwelling children and their families. Other benefits are empowering communities with health literacy and negotiating pathways to tertiary care.
Home high-flow therapy during recovery from severe chronic obstructive pulmonary disease (COPD) exacerbation: a mixed-methods feasibility randomised control trial
Authors: D'Cruz Rebecca F , Rossel Anne , Kaltsakas Georgios , Suh Eui-Sik , Douiri Abdel , Rose Louise , Murphy Patrick B , Hart Nicholas
Published: January 2025

Introduction

Patients recovering from severe acute exacerbations of chronic obstructive pulmonary disease (AECOPD) have a 30-day readmission rate of 20%. This study evaluated the feasibility of conducting a randomised controlled trial to evaluate clinical, patient-reported and physiological effects of home high-flow therapy (HFT) in addition to usual medical therapy, in eucapnic patients recovering from AECOPD to support the design of a phase 3 trial.

Methods

A mixed-methods feasibility randomised controlled trial (quantitative primacy, concurrently embedded qualitative evaluation) (ISRCTN15949009) recruiting consecutive non-obese patients hospitalised with AECOPD not requiring acute non-invasive ventilation. Participants were randomised to receive usual care or usual care and home HFT (37°C, 30 L/min) with weekly home-based follow-up for 4 weeks to collect data on: device usage, breathlessness (modified Borg scale, visual analogue scale, Multidimensional Dyspnoea Profile), health-related quality of life (COPD Assessment Test (CAT), Clinical COPD Questionnaire), pulse oximetry, spirometry and inspiratory capacity, parasternal electromyography and actigraphy. Semistructured interviews were conducted in week 4. Trial progression criteria were: ≥40% of eligible patients randomised, ≤20% attrition, ≥70% complete data, and no device-related serious adverse events (SAE).

Results

18 of 45 eligible patients were randomised (age 69±5 years, 44% female, body mass index 23±5 kg/m2, forced expiratory volume in 1 second 32±12%). One withdrew following non-respiratory hospitalisation. Complete outcome measures were collected in >90% of home assessments. There were no device-related SAE. Daily HFT usage was 2.7±2.2 hours in week 1, falling to 2.3±1.4 hours by week 4. Temperature and flow settings were modified for comfort in 6 cases. Higher HFT usage was associated with lower symptom burden (CAT p=0.01). Interviews highlighted ease of device use, reduced salbutamol usage, and improved sputum production and clearance.

Conclusions

The data from this feasibility study support the progression to a phase 3 randomised clinical trial investigating the effect of home (HFT) on admission-free survival in COPD patients recovering from a severe exacerbation.

Trial registration number

The study received ethical approval (REC19/LO/0194) and was prospectively registered (ISRCTN15949009).
Emergency response planning for sudden cardiac arrest in amateur football clubs in Germany (federal state Saarland)
Authors: Egger Florian , Ukaj Ana , Meyer Tim
Published: January 2025

Objective

While emergency care for sudden cardiac arrest (SCA) is strictly regulated in professional football, the situation in amateur football is unclear. This study investigated the emergency readiness for SCA in German amateur football clubs.

Methods

A cross-sectional survey of 253 German amateur football clubs (fifth division and lower) was conducted between January and August 2023. Club representatives participated in a 30-point questionnaire on automated external defibrillator (AED) availability, visibility, purchase, usage, frequency of staff trained in cardiopulmonary resuscitation (CPR) and AED usage, regular CPR and AED training, and the existence of an emergency action plan (EAP).

Results

161 of 253 eligible clubs (64% response rate) participated. An AED was available in 48/161 (30%) clubs. 46 of 161 clubs (29%) had no CPR-trained staff. A high availability of CPR- and AED-trained staff (>75% likelihood of being present at the pitch) was more likely during a match (61% and 84%) than training (40% and 51%), respectively. Retrospectively, over 7 years, five clubs reported that CPR-trained staff used an AED, resulting in a survival rate of 80%. 16 clubs (10%) had an EAP in the event of an SCA.

Conclusion

German amateur football clubs show low emergency readiness for SCA despite a promising survival rate when an AED is used by CPR-trained staff on-site. Regular CPR and AED training for club members, increased availability of AEDs, and the development of EAPs might be beneficial in responding adequately to an SCA during football training and matches.
Targeted inhibition of Aurora kinase A promotes immune checkpoint inhibition efficacy in human papillomavirus-driven cancers
Authors: Ghosh Soma , O'Hara Madison P , Sinha Pragya , Mazumdar Tuhina , Yapindi Lacin , Sastry Jagannadha K , Johnson Faye M
Published: January 2025

Background

Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent preclinical models of HPV-driven cancers.

Methods

We assessed the induction of apoptosis, DNA damage, and immunogenic cell death (ICD) in response to treatment with the Aurora A inhibitor alisertib in vitro and antitumor efficacy of alisertib as a monotherapy and in combination with ICIs that inhibit programmed cell death protein-1 (PD-1) or cytotoxic T-lymphocyte associated protein 4 (CTLA-4) in murine HPV-positive immune-competent tumor models. In each treatment group, we determined the tumor growth kinetics and long-term survival and assessed the tumor immune microenvironment using polychromatic flow cytometry.

Results

Aurora A inhibition induced apoptosis, DNA damage, and ICD in vitro in multiple human and murine HPV-positive cancer cell lines. Importantly, Aurora A inhibition induced selective apoptotic depletion of myeloid-derived suppressor cells (MDSCs). In vivo experiments demonstrated that the combination of alisertib with ICIs, specifically anti-CTLA4, resulted in improved survival outcomes by altering the tumor immune microenvironment. This combination enhanced CD8 T-cell infiltration and decreased the frequencies of MDSCs, whereas neither alisertib nor ICIs (anti-PD-1/anti-CTLA-4) alone showed such effects.

Conclusion

Our study establishes the potential of Aurora A inhibition to sensitize HPV-positive tumors to ICIs, specifically anti-CTLA-4 treatment. This combination strategy resulted in enhanced antitumor efficacy, driven by systemic and intratumoral increases in CD8 T-cell responses and reduced immunosuppressive cell populations, specifically MDSCs. These findings offer insights into the synergistic effects of Aurora A inhibition and ICIs and argue for further investigation and optimization of this combination approach in HPV-driven cancers.
Anti-PD-1 amplifies costimulation in melanoma-infiltrating Th1-like Foxp3+regulatory T cells to alleviate local immunosuppression
Authors: Attias Mikhaël , Alvarez Fernando , Al-Aubodah Tho-Alfakar , Istomine Roman , McCallum Paige , Huang Fan , Sleiman Abrahim , Nishimura Tamiko , del Rincón Sonia V , Riazalhosseini Yasser , Piccirillo Ciriaco A
Published: January 2025

Background

Immune checkpoint inhibitors targeting programmed cell death protein-1 (PD-1) are the first line of treatment for many solid tumors including melanoma. PD-1 blockade enhances the effector functions of melanoma-infiltrating CD8+T cells, leading to durable tumor remissions. However, 55% of patients with melanoma do not respond to treatment. As Foxp3+regulatory T (Treg) cells play an important role in tumor-induced immunosuppression and express PD-1, we hypothesized that anti-PD-1 also increases the functions of melanoma-infiltrating Tregcells, which could be detrimental to treatment efficacy.

Methods

The cellular and functional dynamics of Tregcells were evaluated in C57Bl/6 Foxp3-reporter mice bearing highly immunogenic and PD-1 blockade-sensitive Yale University Mouse Melanoma Exposed to Radiation 1.7 (YUMMER1.7) tumors. Tregcell responses in tumors and lymphoid compartments were examined throughout tumor growth or therapy and were assessed ex vivo by multiparametric flow cytometry analysis, with in vitro suppression assays using tumor-infiltrating lymphocytes isolated by fluorescence-activated cell sorting (FACS) andin situthrough spatial proteomic and transcriptomic profiling.

Results

In this highly immunogenic melanoma model, anti-PD-1 monotherapy yielded high responders (HRs) and low responders (LRs). We show that the potent CD8+T cell responses characteristic of HR tumors paradoxically coincide with the expansion of highly-activated, Helios-expressing Tregcells. In both HRs and LRs, Tregcells co-localize with CD8+T cells in immunogenic regions of the tumor and display potent suppressive capacity in vitro. Further characterization revealed that melanoma-infiltrating Tregcells progressively acquire T-bet and interferon gamma expression, exclusively in HRs, and induction of this T helper cell 1 (Th1)-like phenotype in vitro led to CD8+T cell evasion from Tregcell-mediated suppression. Using spatial proteomic and transcriptomic profiling, we demonstrate that Tregcells display an increased activity of PI3K/Akt signaling in regions of HR tumors with an elevated CD8:Tregcell ratio.

Conclusions

PD-1 blockade promotes the expansion of a subset of highly-activated Tregcells coexpressing PD-1 and Helios. While these cells are potently suppressive outside tumor environments, costimulatory and inflammatory signals present in the tumor microenvironment lead to their local acquisition of Th1-like characteristics and loss of suppression of effector T cells.
CREB3L1 facilitates pancreatic tumor progression and reprograms intratumoral tumor-associated macrophages to shape an immunotherapy-resistance microenvironment
Authors: Xu Haiyan , Xue Shengbai , Sun Yang , Ma Jingyu , Li Shumin , Wang Yanling , Mao Tiebo , Ge Weiyu , Yue Ming , Shentu Daiyuan , Lu Wenxin , Wang Yongchao , Hu Jiong , Cui Jiujie , Zhang Xiaofei , Cai Li , Wang Yu , Wang Liwei
Published: January 2025

Background

To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play a vital role in carcinogenesis. However, it remains unclear whether they are involved in pancreatic ductal adenocarcinoma (PDAC) and how they relate to clinical outcomes. This study aims to investigate the biological function and mechanism of how a novel UPR sensor, CREB3L1 works in PDAC and further evaluate its clinical application prospect.

Methods

We tested UPR signaling including CREB3L1 in Thapsigargin-treated PDAC cells. Subsequently, we defined CREB3L1 expression and further analyzed its expression with clinical characteristics in PDAC. Then, we established gene-modified cells to determine whether CREB3L1 functions in cell proliferation and migration capacity. Besides, we constructed subcutaneously and orthotopically transplanted mice models to verify their progrowing function and pulmonary metastasis models to prove their proinvasion role. What’s more, RNAseq, qPCR, Western blotting, immunohistochemistry and multicolor flow cytometry experiments were used to explore the mechanism of how CREB3L1 worked in PDAC. Lastly, CREB3L1 expression correlation with PDAC immunotherapy outcome and immune cell signatures were explored in the patients with advanced PDAC who received PD-1 antibody therapy.

Results

We first confirmed CREB3L1 could be induced by endoplasmic reticulum stressor and found its aberrant activation was associated with poorer overall survival in PDAC patients indicating the protumor function of the new UPR sensor. Functionally, we confirmed CREB3L1 contributing to PDAC malignant progression including growth and metastasis by multiple in in vitro and in vivo models. Mechanistically, CREB3L1 upregulated COL3A1 and promoted dense stroma formation for facilitating PDAC and knocking down COL3A1 disrupted CREB3L1 protumor function. Furthermore, CREB3L1-induced TAM polarization toward an M2 phenotype and reduced the infiltration of CD8+T cells. Clinically, CREB3L1 correlated with immune cell signatures as well as immune checkpoint blockade (ICB) treatment response and outcome that CREB3L1aberrant activation indicated poorer efficacy and worse prognosis than the low in PDAC which might empower clinical decision.

Conclusions

Collectively, this study revealed CREB3L1 facilitated PDAC progression, shaped an immune exclude tumor microenvironment and distinguished therapy response and outcome of ICB therapy indicating CREB3L1 could be a promising novel molecular target and biomarker for PDAC treatment.
Nivolumab plasma concentration and clearance associated with overall survival in patients with renal cell carcinoma
Authors: Maritaz Christophe , Combarel David , Dalban Cécile , Blondel Louis , Broutin Sophie , Marabelle Aurelien , Albiges Laurence , Paci Angelo
Published: January 2025

Background

Nivolumab is an immune checkpoint inhibitor (ICI) that selectively inhibits programmed cell death protein 1 activation, restoring antitumor immunity. ICIs are indicated for various types of advanced solid tumors; however, not all patients benefit from them, and tools that could be used in the clinic to predict response to treatment represent an unmet need. Here we describe the development of a new population pharmacokinetic (PPK) model in patients treated with nivolumab in clinical trials. Applying the model to a patient population with renal cell carcinoma identified nivolumab clearance and plasma concentration as predictors of overall survival (OS).

Methods

A custom liquid chromatography with tandem mass spectrometry method for quantifying nivolumab plasma concentration was developed and validated following the European Medicines Agency guidelines for bioanalytical method validation. The PPK model was developed using data from patients treated in the NIVIPIT (n=38) and NIVOREN (n=137) trials of nivolumab in metastatic melanoma and renal cell carcinoma, respectively. The PPK model was used to determine pharmacokinetic (PK) parameters such as baseline clearance and simulate individual clearance changes over time. The relationship between PK characteristics (including clearance at Cycle 1 (CLC1), plasma concentration at Cycle 3 and clinical outcomes was assessed in 137 patients treated in NIVOREN. Kaplan-Meier methodology was used in time-to-event analyses.

Results

In 137 patients, the median nivolumab CLC1 was 6 mL/hour and the median plasma concentration at Cycle 3 was 48 µg/mL. Median follow-up was 21.0 months (95% CI 20.2 to 22.5 months) with a survival rate at 6 months of 91.2% and 77.9% at 12 months. In univariate analysis, OS was significantly higher in patients with CLC1<6 mL/hour versus ≥6 mL/hour (HR 2.2 (95% CI 1.2 to 4.1), p=0.0146). Shorter OS was observed in patients with plasma concentration at Cycle 3 below the median (48 µg/mL) versus those above the median (HR 0.4 (95% CI 0.2 to 0.8), p=0.0069). Multivariate analysis showed a trend towards lower clearance, but this did not reach statistical significance (p=0.0694).

Conclusions

Results of the study may potentially be used to predict outcomes of nivolumab therapy in patients with renal cell carcinoma. Additional applications may include guiding dose adjustments of nivolumab in those who are less likely to respond to the initial dose.
Association between resolution of MRI-detected inflammation and improved clinical outcomes in axial spondyloarthritis under long-term anti-TNF therapy
Authors: Torgutalp Murat , Rademacher Judith , Proft Fabian , Hermann Kay-Geert , Althoff Christian , Haibel H , Protopopov Mikhail , Sieper Joachim , Rios Rodriguez Valeria , Poddubnyy Denis
Published: January 2025

Objectives

In this post-hoc analysis of ESTHER trial, we aimed to investigate the longitudinal relationship between inflammation on MRI and the achievement of inactive disease/low disease activity in patients with axial spondyloarthritis (axSpA) treated with long-term tumor necrosis factor (TNF) inhibitor etanercept.

Methods

Of the 76 patients with active axSpA in the ESTHER trial, we included all patients treated with etanercept for at least 6 months for main analysis. All clinical and MRI data from 4.5 years of follow-up were used in the analysis. MRIs of the spine and sacroiliac (SI) joints were performed at baseline, week 24, week 48 and yearly thereafter and were evaluated for active inflammatory lesions according to the Berlin MRI score.

Results

Longitudinal analysis showed that higher SI joint osteitis score was associated with higher Axial Spondyloarthritis Disease Activity Score (ASDAS) at the same time point (β=0.08, 95% CI (0.05; 0.11)) and at the next time point 6 months later (β=0.05, 95% CI (0.02; 0.07)). Furthermore, resolution of osteitis in the SI joint (Berlin MRI osteitis score of ≤1) was associated with lower ASDAS at the next time point (β=−0.26, 95% CI (−0.42; −0.09)), higher odds of achieving ASDAS low disease activity (OR=5.61, 95% CI (1.06; 29.67)) and inactive disease status (OR=2.23, 95% CI (1.01; 4.94)) at the next time point.

Conclusions

The presence of inflammation on SI joints-MRI is associated with higher disease activity in axSpA. Resolution of inflammation on MRI is associated with better clinical outcomes in the long-term follow-up. Thus, achieving complete resolution of inflammation is favourable for meeting the treatment goals in axSpA.

Trial registration number

NCT00844142.
Evaluation of rheumatoid arthritis-associated interstitial lung disease in patients treated with JAK inhibitors: a MAJIK-SFR cohort study
Authors: Triboulet Félicien , Juge Pierre-Antoine , Truchetet Marie-Elise , Pham Thao , Roux Nicolas , Flipo René-Marc , Leské Charles , Roux Christian Hubert , Seror Raphaele , Basch André , Brocq Olivier , Chazerain Pascal , Coury-Lucas Fabienne , Damade Richard , Dernis Emanuelle , Gottenberg Jacques-Eric , Ramon André , Ruyssen-Witrand Adeline , Salmon Jean Hugues , Shipley Émilie , Tournadre Anne , Prati Clement , Dieudé Philippe , Avouac Jerome
Published: January 2025

Objective

To examine the course of interstitial lung disease associated with rheumatoid arthritis (RA-ILD) in France on treatment with Janus kinase inhibitors (JAKis) using the MAJIK-SFR registry.

Methods

Prospective national multicentre observational study identifying patients with RA-ILD from the MAJIK-SFR registry. Pulmonary assessment data were collected at JAKi initiation and follow-up visits (6 months, 12 months and a median of 21 months postinclusion), including chest high-resolution CT (HRCT), pulmonary function tests (forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO)), acute exacerbations of ILD, respiratory infections and lung cancers.

Results

We enrolled 42 patients (26 women, 62%) with RA-ILD with a mean age of 61±13 years and a mean disease duration of 16±10 years. Compared with the 778 RA patients without ILD from the MAJIK registry, RA-ILD patients were older, displayed more severe and active disease and had more prevalent comorbidities. Non-specific interstitial pneumonia and usual interstitial pneumonia accounted for 46% and 43% of the chest HRCT ILD patterns, respectively. No significant changes in FVC and DLCO were observed during the follow-up period. Chest HRCT lesions remained stable in 69% of patients. Progressive ILD was identified in 8 patients (19%). 16 (38%) respiratory tract infections were observed. Only one acute regressive exacerbation of ILD was noted, and no lung cancer was diagnosed. No deaths occurred. JAKi was discontinued in 17 patients including 8 for inefficacy on joint involvement and 5 for intolerance.

Conclusion

The analysis indicates stability of RA-ILD in patients treated with JAKi. The tolerance profile of JAKi in this higher risk population did not reveal new safety signal.
Combination of clinical factors predicts successful glucocorticoid withdrawal in systemic lupus erythematosus (SLE): results from a multicentre, retrospective cohort study
Authors: Katechis Spyridon , Pitsigavdaki Sofia , Nikoloudaki Myrto , Silvagni Ettore , Repa Argyro , Marangoni Antonio , Flouri Irini , Avgoustidis Nestor , Parperis Konstantinos , Govoni Marcello , Sidiropoulos Prodromos , Boumpas Dimitrios T , Fanouriakis Antonis , Bertsias George , Bortoluzzi Alessandra
Published: January 2025

Objective

Glucocorticoid (GC) tapering and withdrawal to reduce damage represents a key aspect of the European Alliance of Associations for Rheumatology (EULAR) SLE recommendations. However, optimal strategies for relapse-free GC cessation remain ill-defined. We characterised clinical predictors and their combined effect on flares in patients with SLE who discontinued GC.

Methods

Retrospective cohort of 324 patients with active SLE (PGA ≥1.5 and/or SLEDAI-2K ≥6) who received GC as part of treatment intensification (median follow-up 60 months). Survival and generalised linear models estimated SELENA-SLEDAI flare risks and their predictors.

Results

GCs were discontinued in 220 (67.9%) patients with 1-year risks for overall and severe flares of 50% and 25%, respectively (HR: 1.48; 95% CI: 1.12 to 1.96 for overall flares; HR: 1.52; 95% CI: 1.03 to 2.25 for severe flares, compared with non-withdrawers). Flare risk was lowered when GCs were ceased during remission (DORIS) or Lupus Low Disease Activity State (LLDAS; excluding remission) (HR for severe flares: 0.23; 0.12 to 0.43 and 0.30; 0.18 to 0.50, respectively), with each additional month in targets providing further protection. Hydroxychloroquine prevented total (HR: 0.37; 0.26 to 0.53) and severe flares (HR: 0.33; 0.21 to 0.52), while mycophenolate and azathioprine reduced overall flares. Prednisone tapering from 7.5 mg/day to 0 over >6 months improved severe flare-free outcome (HR: 0.57; 0.37 to 0.90). Random survival forests identified DORIS/LLDAS, hydroxychloroquine use and slow GC tapering as top predictors, whose coexistence reduced overall and severe flares by ~25 fold and ~50 fold, respectively. This combination reduced damage (IRR: 0.31; 0.08 to 0.84) without inducing flares (IRR: 0.52; 95% CI: 0.18 to 1.16) compared with GC non-withdrawers.

Conclusion

Low or absent disease activity, slow tapering and hydroxychloroquine use minimise the risk of flares, facilitating GC discontinuation—a major goal in SLE.