Murine orthotopic lung transplant models: A comprehensive overview of genetic mismatch degrees and histopathological insights into chronic lung allograft dysfunction.

Currently, lung transplantation outcome remains inferior compared to other solid organ transplantations. A major cause for limited survival after lung transplantation is chronic lung allograft dysfunction. Numerous animal models have been developed to investigate chronic lung allograft dysfunction to discover adequate treatments. The murine orthotopic lung transplant model has been further optimized over the last years. However, different degrees of genetic mismatch between donor and recipient mice have been used, applying a single, minor, moderate, and major genetic mismatch. This review aims to reassess the existing murine mismatch models and provide a comprehensive overview, with a specific focus on their eventual histopathological presentation. This will be crucial to leverage this model and tailor it according to specific research needs.

Measurement properties of utility-based health-related quality of life measures in cardiac rehabilitation and secondary prevention programs: a systematic review.

PURPOSE: To identify utility-based patient-reported outcome measures (PROMs) for assessing health-related quality of life (HRQoL) in cardiac rehabilitation and secondary prevention programs (CR) and appraise existing evidence on their measurement properties. Secondly, to link their items to the International Classification of Functioning Disability and Health (ICF) and the International Consortium of Health Outcome Measures (ICHOM) domains for cardiovascular disease (CVD). METHODS: Eight databases were searched. The review followed the COSMIN and JBI guidelines for measurement properties systematic reviews and PRISMA 2020 reporting guidelines. Non-experimental and observational empirical studies of patients ≥ 18 years of age with CVD undergoing CR and assessed quality of life (QoL) or HRQoL using utility-based PROMs or one accompanied by health state utilities were included. RESULTS: Nine PROMs were identified with evidence on measurement properties for three measures: the German translations of SF-12, EQ-5D-5L, and MacNew heart disease HRQoL questionnaire. There was moderate quality evidence for responsiveness and hypothesis testing of the SF-12 and EQ-5D-5L, and high-quality evidence for responsiveness and hypothesis testing for the MacNew. All items of SF-12 and EQ-5D were linked to ICF categories, but four items of the MacNew were not classified or defined. All the PROM domains were mapped onto similar constructs from the ICHOM global sets. CONCLUSION: Three utility-based PROMs validated in CR were identified: the German versions of the EQ-5D and SF-12 and the MacNew questionnaire. These PROMs are linked to a breadth of ICF categories and all ICHOM global sets. Additional validation studies of PROMs in CR are required.

Care biography: A concept analysis.

In this article, we investigate how the concept of Care Biography and related concepts are understood and operationalised and describe how it can be applied to advancing our understanding and practice of holistic and person-centred care. Walker and Avant's eight-step concept analysis method was conducted involving multiple database searches, with potential or actual applications of Care Biography identified based on multiple discussions among all authors. Our findings demonstrate Care Biography to be a novel overarching concept derived from the conjunction of multiple other concepts and applicable across multiple care settings. Concepts related to Care Biography exist but were more narrowly defined and mainly applied in intensive care, aged care, and palliative care settings. They are associated with the themes of Meaningfulness and Existential Coping, Empathy and Understanding, Promoting Positive Relationships, Social and Cultural Contexts, and Self-Care, which we used to inform and refine our concept analysis of Care Biography. In Conclusion, the concept of Care Biography, can provide a deeper understanding of a person and their care needs, facilitate integrated and personalised care, empower people to be in control of their care throughout their life, and help promote ethical standards of care.

Clinical service organisation for adults with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is an increasingly prevalent heart rhythm condition in adults. It is considered a common cardiovascular condition with complex clinical management. The increasing prevalence and complexity in management underpin the need to adapt and innovate in the delivery of care for people living with AF. There is a need to systematically examine the optimal way in which clinical services are organised to deliver evidence-based care for people with AF. Recommended approaches include collaborative, organised multidisciplinary, and virtual (or eHealth/mHealth) models of care. OBJECTIVES: To assess the effects of clinical service organisation for AF versus usual care for people with all types of AF. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and CINAHL to October 2022. We also searched ClinicalTrials.gov and the WHO ICTRP to April 2023. We applied no restrictions on date, publication status, or language. SELECTION CRITERIA: We included randomised controlled trials (RCTs), published as full texts and as abstract only, involving adults (≥ 18 years) with a diagnosis of any type of AF. We included RCTs comparing organised clinical service, disease-specific management interventions (including e-health models of care) for people with AF that were multicomponent and multidisciplinary in nature to usual care. DATA COLLECTION AND ANALYSIS: Three review authors independently selected studies, assessed risk of bias, and extracted data from the included studies. We calculated risk ratio (RR) for dichotomous data and mean difference (MD) or standardised mean difference (SMD) for continuous data with 95% confidence intervals (CIs) using random-effects analyses. We then calculated the number needed to treat for an additional beneficial outcome (NNTB) using the RR. We performed sensitivity analyses by only including studies with a low risk of selection and attrition bias. We assessed heterogeneity using the I² statistic and the certainty of the evidence according to GRADE. The primary outcomes were all-cause mortality and all-cause hospitalisation. The secondary outcomes were cardiovascular mortality, cardiovascular hospitalisation, AF-related emergency department visits, thromboembolic complications, minor cerebrovascular bleeding events, major cerebrovascular bleeding events, all bleeding events, AF-related quality of life, AF symptom burden, cost of intervention, and length of hospital stay. MAIN RESULTS: We included 8 studies (8205 participants) of collaborative, multidisciplinary care, or virtual care for people with AF. The average age of participants ranged from 60 to 73 years. The studies were conducted in China, the Netherlands, and Australia. The included studies involved either a nurse-led multidisciplinary approach (n = 4) or management using mHealth (n = 2) compared to usual care. Only six out of the eight included studies could be included in the meta-analysis (for all-cause mortality and all-cause hospitalisation, cardiovascular mortality, cardiovascular hospitalisation, thromboembolic complications, and major bleeding), as quality of life was not assessed using a validated outcome measure specific for AF. We assessed the overall risk of bias as high, as all studies had at least one domain at unclear or high risk of bias rating for performance bias (blinding) in particular. Organised AF clinical services probably result in a large reduction in all-cause mortality (RR 0.64, 95% CI 0.46 to 0.89; 5 studies, 4664 participants; moderate certainty evidence; 6-year NNTB 37) compared to usual care. However, organised AF clinical services probably make little to no difference to all-cause hospitalisation (RR 0.94, 95% CI 0.88 to 1.02; 2 studies, 1340 participants; moderate certainty evidence; 2-year NNTB 101) and may not reduce cardiovascular mortality (RR 0.64, 95% CI 0.35 to 1.19; 5 studies, 4564 participants; low certainty evidence; 6-year NNTB 86) compared to usual care. Organised AF clinical services reduce cardiovascular hospitalisation (RR 0.83, 95% CI 0.71 to 0.96; 3 studies, 3641 participants; high certainty evidence; 6-year NNTB 28) compared to usual care. Organised AF clinical services may have little to no effect on thromboembolic complications such as stroke (RR 1.14, 95% CI 0.74 to 1.77; 5 studies, 4653 participants; low certainty evidence; 6-year NNTB 588) and major cerebrovascular bleeding events (RR 1.25, 95% CI 0.79 to 1.97; 3 studies, 2964 participants; low certainty evidence; 6-year NNTB 556). None of the studies reported minor cerebrovascular events. AUTHORS' CONCLUSIONS: Moderate certainty evidence shows that organisation of clinical services for AF likely results in a large reduction in all-cause mortality, but probably makes little to no difference to all-cause hospitalisation compared to usual care. Organised AF clinical services may not reduce cardiovascular mortality, but do reduce cardiovascular hospitalisation compared to usual care. However, organised AF clinical services may make little to no difference to thromboembolic complications and major cerebrovascular events. None of the studies reported minor cerebrovascular events. Due to the limited number of studies, more research is required to compare different models of care organisation, including utilisation of mHealth. Appropriately powered trials are needed to confirm these findings and robustly examine the effect on inconclusive outcomes. The findings of this review underscore the importance of the co-ordination of care underpinned by collaborative multidisciplinary approaches and augmented by virtual care.

Surgical treatment of thymic epithelial tumors: a narrative review.

Background and Objective: Thymic epithelial tumors (TETs) are scarce neoplasms of the prevascular mediastinum. Included in this diverse category of lesions are thymomas and thymic carcinomas (TCs). Surgery is the mainstay of treatment of tumors that are deemed resectable. However, up till now, optimal surgical access has been a subject of debate. The advent of new techniques, such as video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS), challenged the median sternotomy which was traditionally considered the access of choice. This review aims to demonstrate the current evidence concerning the surgical treatment of TET and to enlighten other controversial issues about surgery. Methods: PubMed research was conducted using the terms [surgery] AND [thymic epithelial tumors] OR [thymomas] and [surgical treatment] AND [thymic epithelial tumors] OR [thymomas]. Papers concerning pediatric cases and non-English literature papers were excluded. Individual case reports were also excluded. Key Content and Findings: Minimally invasive surgical techniques (MIST) such as VATS and RATS are increasingly applied in early-stage TET. Although numerous published studies have demonstrated better perioperative outcomes in early-stage TET, long-term follow-up data are still required to demonstrate the oncological equivalent of MIST to open surgery. Resection of stage III TET is more challenging. Thymectomy can be expanded en bloc to include the major vascular structures, lung, pleura, phrenic, or vagus nerve in these individuals. There is no agreement on the ideal surgical access and traditionally these patients underwent open sternotomy, sometimes combined with a thoracic access. Evidence concerning the treatment of stage IVA disease is mainly derived from retrospective case series which are highly heterogeneous in terms of the number of enrolled patients, histology, degree of pleural involvement, and timing of presentation. Conclusions: New techniques in the field of minimally invasive surgery are gaining acceptance for early-stage TET but longer follow-up periods are warranted to prove their oncological outcomes. On the contrary, these techniques should be used cautiously in case of locally advanced tumors. Surgeons must not forget that the main objective is the complete resection of the lesion, which is one major predictive factor for increased survival.

Clinical effectiveness of cardiac rehabilitation and barriers to completion in patients of low socioeconomic status in rural areas: A mixed-methods study.

OBJECTIVE: To investigate cardiac rehabilitation utilisation and effectiveness, factors, needs and barriers associated with non-completion. DESIGN: We used the mixed-methods design with concurrent triangulation of a retrospective cohort and a qualitative study. SETTING: Economically disadvantaged areas in rural Australia. PARTICIPANTS: Patients (≥18 years) referred to cardiac rehabilitation through a central referral system and living in rural areas of low socioeconomic status. MAIN MEASURES: A Cox survival model balanced by inverse probability weighting was used to assess the association between cardiac rehabilitation utilization and 12-month mortality/cardiovascular readmissions. Associations with non-completion were tested by logistic regression. Barriers and needs to cardiac rehabilitation completion were investigated through a thematic analysis of semi-structured interviews and focus groups (n = 28). RESULTS: Among 16,159 eligible separations, 44.3% were referred, and 11.2% completed cardiac rehabilitation. Completing programme (HR 0.65; 95%CI 0.57-0.74; p < 0.001) led to a lower risk of cardiovascular readmission/death. Living alone (OR 1.38; 95%CI 1.00-1.89; p = 0.048), having diabetes (OR 1.48; 95%CI 1.02-2.13; p = 0.037), or having depression (OR 1.54; 95%CI 1.14-2.08; p = 0.005), were associated with a higher risk of non-completion whereas enrolment in a telehealth programme was associated with a lower risk of non-completion (OR 0.26; 95%CI 0.18-0.38; p < 0.001). Themes related to logistic issues, social support, transition of care challenges, lack of care integration, and of person-centeredness emerged as barriers to completion. CONCLUSIONS: Cardiac rehabilitation completion was low but effective in reducing mortality/cardiovascular readmissions. Understanding and addressing barriers and needs through mixed methods can help tailor cardiac rehabilitation programmes to vulnerable populations and improve completion and outcomes.

Auranofin repurposing for lung and pancreatic cancer: low CA12 expression as a marker of sensitivity in patient-derived organoids, with potentiated efficacy by AKT inhibition.

BACKGROUND: This study explores the repurposing of Auranofin (AF), an anti-rheumatic drug, for treating non-small cell lung cancer (NSCLC) adenocarcinoma and pancreatic ductal adenocarcinoma (PDAC). Drug repurposing in oncology offers a cost-effective and time-efficient approach to developing new cancer therapies. Our research focuses on evaluating AF's selective cytotoxicity against cancer cells, identifying RNAseq-based biomarkers to predict AF response, and finding the most effective co-therapeutic agents for combination with AF. METHODS: Our investigation employed a comprehensive drug screening of AF in combination with eleven anticancer agents in cancerous PDAC and NSCLC patient-derived organoids (n = 7), and non-cancerous pulmonary organoids (n = 2). Additionally, we conducted RNA sequencing to identify potential biomarkers for AF sensitivity and experimented with various drug combinations to optimize AF's therapeutic efficacy. RESULTS: The results revealed that AF demonstrates a preferential cytotoxic effect on NSCLC and PDAC cancer cells at clinically relevant concentrations below 1 µM, sparing normal epithelial cells. We identified Carbonic Anhydrase 12 (CA12) as a significant RNAseq-based biomarker, closely associated with the NF-κB survival signaling pathway, which is crucial in cancer cell response to oxidative stress. Our findings suggest that cancer cells with low CA12 expression are more susceptible to AF treatment. Furthermore, the combination of AF with the AKT inhibitor MK2206 was found to be particularly effective, exhibiting potent and selective cytotoxic synergy, especially in tumor organoid models classified as intermediate responders to AF, without adverse effects on healthy organoids. CONCLUSION: Our research offers valuable insights into the use of AF for treating NSCLC and PDAC. It highlights AF's cancer cell selectivity, establishes CA12 as a predictive biomarker for AF sensitivity, and underscores the enhanced efficacy of AF when combined with MK2206 and other therapeutics. These findings pave the way for further exploration of AF in cancer treatment, particularly in identifying patient populations most likely to benefit from its use and in optimizing combination therapies for improved patient outcomes.

A call for action to include psychosocial management into holistic, integrated care for patients with atrial fibrillation.

Contemporary management of atrial fibrillation (AF) has become increasingly complex. Therefore, strong efforts have been made during the past decade to develop models for structured, integrated care for patients with AF. These have also been incorporated in international guidelines for the management of patients with AF. However, implementation of integrated care approaches in daily clinical practice is scarce and far from optimal, and it may require a re-thinking of the structure of the healthcare system. The reasons for the poor implementation are many, from limited time and economic resources to deficits in postgraduate education of healthcare professionals, lack of involvement of patients in how integrated care should be designed, and fragmentation of the healthcare system. Moreover, patients' psychological challenges, which not only impact patients' adherence to treatment but, if untreated, increase their risk of morbidity, mortality, and poor quality of life, are not given sufficient attention. It is time to start a necessary discussion of what integrated care should be, what it should contain, and what is necessary to implement it in daily clinical practice.

The diagnosis and management of chronic lung allograft dysfunction.

PURPOSE OF REVIEW: Chronic lung allograft dysfunction (CLAD) remains a life-threatening complication following lung transplantation. Different CLAD phenotypes have recently been defined, based on the combination of pulmonary function testing and chest computed tomography (CT) scanning and spurred renewed interests in differential diagnosis, risk factors and management of CLAD. RECENT FINDINGS: Given their crucial importance in the differential diagnosis, we will discuss the latest development in assessing the pulmonary function and chest CT scan, but also their limitations in proper CLAD phenotyping, especially with regards to patients with baseline allograft dysfunction. Since no definitive treatment exists, it remains important to timely identify clinical risk factors, but also to assess the presence of specific patterns or biomarkers in tissue or in broncho alveolar lavage in relation to CLAD (phenotypes). We will provide a comprehensive overview of the latest advances in risk factors and biomarker research in CLAD. Lastly, we will also review novel preventive and curative treatment strategies for CLAD. SUMMARY: Although this knowledge has significantly advanced the field of lung transplantation, more research is warranted because CLAD remains a life-threatening complication for all lung transplant recipients.

Atrial fibrillation: epidemiology, screening and digital health.

Atrial fibrillation (AF) is highly prevalent with a lifetime risk of about 1 in 3-5 individuals after the age of 45 years. Between 2010 and 2019, the global prevalence of AF has risen markedly from 33.5 million to 59 million individuals living with AF. Early detection of AF and implementation of appropriate treatment could reduce the frequency of complications associated with AF. International AF management guidelines recommend opportunistic and systematic screening for AF, but additional data are needed. Digital approaches and pathways have been proposed for early detection and for the transition to early AF management. Mobile health (mHealth) devices provide an opportunity for digital screening and should be part of novel models of care delivery based on integrated AF care pathways. For a broad implementation of mHealth-based, integrated care for patients with chronic diseases as AF, further high quality evidence is necessary. In this review, we present an overview of the present data on epidemiology, screening techniques, and the contribution of digital health solutions to the integrated management of AF. We also provide a systemic review on current data of digital and integrated AF management.

A systematic review of patient-derived tumor organoids generation from malignant effusions.

This review assesses the possibility of utilizing malignant effusions (MEs) for generating patient-derived tumor organoids (PDTOs). Obtained through minimally invasive procedures MEs broaden the spectrum of organoid sources beyond resection specimens and tissue biopsies. A systematic search yielded 11 articles, detailing the successful generation of 190 ME-PDTOs (122 pleural effusions, 54 malignant ascites). Success rates ranged from 33% to 100%, with an average of 84% and median of 92%. A broad and easily applicable array of techniques can be employed, encompassing diverse collection methods, variable centrifugation speeds, and the inclusion of approaches like RBC lysis buffer or centrifuged ME supernatants supplementation, enhancing the versatility and accessibility of the methodology. ME-PDTOs were found to recapitulate primary tumor characteristics and were primarily used for drug screening applications. Thus, MEs are a reliable source for developing PDTOs, emphasizing the need for further research to maximize their potential, validate usage, and refine culturing processes.

Patient journey mapping: emerging methods for understanding and improving patient experiences of health systems and services.

Patient journey mapping is an emerging field of research that uses various methods to map and report evidence relating to patient experiences and interactions with healthcare providers, services, and systems. This research often involves the development of visual, narrative, and descriptive maps or tables, which describe patient journeys and transitions into, through, and out of health services. This methods corner paper presents an overview of how patient journey mapping has been conducted within the health sector, providing cardiovascular examples. It introduces six key steps for conducting patient journey mapping and describes the opportunities and benefits of using patient journey mapping and future implications of using this approach.

Changes in healthcare utilisation during implementation of remote atrial fibrillation management: TeleCheck-AF project.

AIM: To evaluate changes in healthcare utilisation and comprehensive packages of care activities and procedures (referred in the Netherlands to as 'diagnose-behandelcombinatie (DBC) care products) during the implementation of the TeleCheck-AF approach (teleconsultation supported by app-based heart rate/rhythm monitoring) in a Dutch atrial fibrillation (AF) clinic. METHODS AND RESULTS: In the Maastricht University Medical Centre+ AF Clinic, data on healthcare utilisation and DBC care products for patients consulted by both a conventional approach in 2019 and the TeleCheck-AF approach in 2020 were analysed. A patient experience survey was performed. Thirty-seven patients (median age 68 years; 40% women) were analysed. With the conventional approach, 35 face-to-face consultations and 0 teleconsultations were conducted. After the implementation of TeleCheck-AF, the number of face-to-face consultations dropped by 80% (p < 0.001) and teleconsultations increased to 45 (p < 0.001). While 42 electrocardiograms (ECGs) and 25 Holter ECGs or echocardiograms were recorded when using the conventional approach, the number of ECGs decreased by 71% (p < 0.001) and Holter ECGs or echocardiograms by 72% (p < 0.001) with the TeleCheck-AF approach. The emergency department patient presentations showed no statistically significant change (p = 0.33). Overall, 57% of medium-weight DBC care products were changed to light-weight ones during implementation of the TeleCheck-AF approach. Patient satisfaction with the TeleCheck-AF approach was high. CONCLUSION: The implementation of TeleCheck-AF led to a change in healthcare utilisation, a change from medium-weight to light-weight DBC care products and a reduction in patient burden. These results created the basis for a new reimbursement code for the TeleCheck-AF approach in the Netherlands.

Understanding for whom, under what conditions, and how an integrated approach to atrial fibrillation service delivery works: a realist review.

AIMS: To understand for whom, under what conditions, and how an integrated approach to atrial fibrillation (AF) service delivery works (or does not work). METHODS AND RESULTS: A realist review of integrated approaches to AF service delivery for adult populations aged ≥18 years. An expert panel developed an initial programme theory, searched and screened literature from four databases until October 2022, extracted and synthesized data using realist techniques to create context-mechanism-outcome configurations for integrated approaches to AF service, and developed an integrated approach refined programme theory. A total of 5433 documents were screened and 39 included. The refined programme theory included five context-mechanism-outcome configurations for how clinical and system-wide outcomes are affected by the way integrated approaches to AF service delivery are designed and delivered. This review identifies core mechanisms underpinning the already known fundamental components of integrated care. This includes having a central coordinator responsible for service organization to provide continuity of care across primary and secondary care ensuring services are patient centred. Additionally, a fifth pillar, lifestyle and risk factor reduction, should be recognized within an AF care pathway. CONCLUSION: It is evident from our provisional theory that numerous factors need to interlink and interact over time to generate a successfully integrated model of care in AF. Stakeholders should embrace this complexity and acknowledge that the learnings from this review are integral to shaping future service delivery in the face of an aging population and increased prevalence of AF.