Background: ESKD is a total or near-permanent failure in renal function. It is irreversible, progressive and ultimately fatal without peritoneal dialysis (PD), haemodialysis (HD) or kidney transplantation. Dialysis treatments can create new and additional problems for patients, one of which is foot amputation, as a result of non-healing wounds and vascular complications. The association between dialysis therapy and foot ulceration is linked to several factors: physical and psychological health; peripheral arterial disease (PAD); mobility; tissue oxygenation; manual dexterity; neuropathy; visual acuity; anaemia; nutrition; leg oedema; hypoalbuminemia; infection; inadequacy of dialysis; and leg/foot support during dialysis. The potential risk factors for foot ulceration may include: not routinely receiving foot care education; incorrect use of footwear; diabetes duration; neuropathy; and peripheral arterial disease. Aim: The aim of this review is to examine the factors that help or hinder successful implementation of foot care education programmes for ESKD patients receiving haemodialysis. Method: A comprehensive literature search was completed using five electronic databases. Medline; CINAHL; Embase; PsycINFO; and Cochrane Library. The Joanna Briggs Institute checklist (JBI) was used to quality appraise full text papers included in the review. The systematic review was not limited to specific categories of interventions to enable optimal comparison between interventions and provide a comprehensive overview of the evidence in this important field of foot care. Results: We found no previously published studies that considered foot care education programmes for haemodialysis patients who are not diabetic; thus, the present systematic review examined four studies on diabetic patients receiving haemodialysis exposed to foot care education programmes from various types of intervention designs. Conclusions: This systematic review has provided evidence that it is possible to influence foot care knowledge and self-care behaviours in both diabetic patients receiving haemodialysis and healthcare professionals. End-stage kidney disease (ESKD) is a worldwide public health issue characterised by significant impairment of kidney function . Foot prESKD is a total or near-permanent failure in renal function. It is irreversible, progressive and ultimately fatal without peritoneal dialysis (PD), haemodialysis (HD) or kidney transplantation . From 20However, dialysis treatments can create new and additional problems for patients, one of which is foot amputation, as a result of non-healing wounds and vascular complications . AmputatIn one observational study, dialysis nurses implemented a routine foot check in patients with diabetes on haemodialysis in the haemodialysis unit as part of standard clinic care at Fresenius Medical Care North America clinics and reported an association between prevalent foot ulceration and haemodialysis therapy . The potPatient education plays a vital role in nursing practice and can impact patient health and quality of life positively . FurtherMultiple studies suggest that patient education regarding foot care is effective in preventing foot ulcers and amputation in diabetic patients ,17,18,19To sum up, foot ulceration, amputation and other serious complications necessitate development of educational interventions to increase knowledge and shape behaviours in ESKD patients concerning foot ulceration risk factors, as well as promotion of self-care knowledge and positive foot self-care behaviours. The goal of educational interventions is to help ESKD patients receiving haemodialysis change behaviours to reduce the incidence of foot ulceration and amputation . PodiatrFoot care education programmes for diabetic patients are common, as diabetic foot ulceration is one of the major complications of diabetes. However, less is known about foot care education programmes for ESKD patients receiving haemodialysis despite the fact that patients with DM and without ESKD have prevalence rates of risk factors similar to those in ESKD patients without DM . FurtherThe search strategy was not limited to a set time frame. A systematic review search strategy was completed between December 2019 and May 2022 with the assistance of a university librarian. Studies were identified after a search of the following electronic databases: Medline; CINAHL; Embase; PsycINFO; and Cochrane Library. The search focussed on advanced searches using Boolean logic with the logical operators ‘AND’ and ‘OR’ see . Google Study participants who were aged over 18 years, diagnosed with ESKD and receiving dialysis.Education programmes in relation to preventing foot ulceration/amputation in patients receiving dialysis.Education programmes conducted by healthcare staff .Randomised control trials (RCTs), quasi-randomised controlled trials, experimental study designs  and prospective observational studies for inclusion (but not case reports).Published in English (because of limited resources for language translation).No criteria on year of publication were employed.Only primary studies were included; researcher opinion papers, reviews, dissertations, editorials and conference abstracts were excluded.This review included studies with the following characteristics:The systematic review protocol was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and flowchart  see Fig.During the identification phase, 504 publications were identified, of which 110 were duplicates and were removed, leaving a total of 394 titles and abstracts from all databases that four authors  initially screened independently for eligibility using inclusion and exclusion criteria. After initial screening, the review team read 15 full-text articles and discussed the content to assess suitability for inclusion and resolve any disagreements concerning inclusion or exclusion. At this stage, 11 studies were excluded, as they did not meet the eligibility criteria; thus, four studies ultimately were included in the final review.The final phase of the process involved appraising the research quality of the four studies selected for inclusion.The JBI’s Critical Appraisal Checklist for Randomised Controlled Trials and Non-Randomised Controlled Studies  was used to evaluate all included studies critically . JBI is The JBI’s Critical Appraisal Tool for Analytical Quasi-Experimental Studies was used to screen the final list of quasi-experimental studies across different domains, including cause and effect, similarity of participants, similarity of treatment received other than the intervention being studied, control groups, pre- and post-intervention measurements, follow-up, consistency of participant measurement, reliability of outcome measurement and appropriateness of statistical analyses performed see .The review team assigned specific ratings to each of the included studies and evaluated each study as low, moderate or high quality. Rating scores were calculated by collecting the number of ‘yes’ responses to all individual criteria. Overall quality was measured by aggregating the number of ‘yes’ answers in all individual criteria. Depending on the criteria, studies could receive a score of up to 9. A score greater than 5 indicated a high-quality study, a score between 3 and 5 indicated a moderate-quality study and a score lower than 3 suggested a low-quality study.Using the appropriate JBI tool, the first named author (L.A.) implemented the first quality assessment of all included studies, which the review team  then reviewed.Data extraction is a method that describes the collection of necessary information about study characteristics and findings from studies included in a systematic review . In thisA narrative synthesis of research findings was conducted due to the diversity of the chosen methodology, interventions, topics, data heterogeneity and method of reporting outcomes.Altogether, 504 papers were identified from five databases. After 110 duplicates were removed, the remaining 394 studies were screened based on titles and abstracts, of which 379 were excluded, and then the remaining 15 were subjected to a full-text review. Another 11 did not meet the inclusion criteria after the full-text screening. Of these, one focussed on diabetic renal transplant patients , and fouTwo studies were conducted in the United Kingdom ,29, one The study participants were mainly patients, and the patient groups studied were those with diabetes and receiving haemodialysis ,27,28,29Instruments were used to measure outcomes across the studies reviewed in this article to evaluate knowledge behavioural outcomes following foot care education interventions. Most researchers used a questionnaire as their research tool. To evaluate behavioural outcomes, two studies used the Nottingham Assessment of Functional Footcare (NAFF) Questionnaire ,29. The From the existing literature, the duration of educational interventions and follow-ups ranged from four to eight months. Intervention evaluations were conducted every two months ,29, fourFour authors  assessed methodological quality independently using the appropriate JBI checklist, and assessment discrepancies were resolved through joint discussions until consensus was reached. If study sections were judged to be unclear (U) or not applicable (NA), they were assigned zero points, with total scores for each study on their corresponding scales tabulated. The scales used to grade papers assessed methodological processes, including the quality of literature search strategies, data presentation and use of consecutive participant inclusion. While this approach does not provide a comprehensive critical appraisal of a paper, it enables standard comparisons between papers. Each reviewed study’s methodological quality is summarised in . The stuThe educational interventions’ programme structure, delivery, content and implementation were analysed.n = 2) [n = 1) [n = 1) [n = 3) [One study used foot care education programmes as the intervention, comprising multiple education sessions  of varying frequency and duration  see Tab. Educatin = 2) ,27; grou [n = 1) ; and/or  [n = 3) ,29. A de [n = 3) ,27 and p [n = 3) . Foot ca [n = 3) ,27,28,29 [n = 3) ,28,29.All four studies focussed on assessing patients’ feet and providing foot care information to patients. The procedures for the educational interventions in each reviewed study are summarised in Brand et al.  showed oBrand et al.  showed oReda et al.  showed oNeil et al.  showed oEducational foot care interventions generally elicited positive outcomes see . The effIn terms of foot care knowledge outcomes, one study assessed the foot education programme’s impact on patients’ foot care knowledge . This stAll four studies highlighted the effect of patient education on foot self-care behaviours.Neil et al.  used a cTwo studies highlighted the effects from foot examinations by nurses, with change occurring following the intervention programme, suggesting that education provided by nurses encouraged study participants to conduct more regular foot examinations ,29. WhenThe four studies in this review reported that lower limb problems improved following educational interventions ,27,28,29Foot care referral pathways to podiatry increased in diabetic patients receiving haemodialysis ,29 see . No refeTo sum up, foot care education programmes reported in previous research indicated improvements in foot self-care knowledge, foot self-care behaviours, foot examination, rates of lower limb problems and referral rates in older ESKD patients receiving haemodialysis and haemodialysis nursing staff.Four studies found several barriers that affected implementation of educational interventions in foot care programmes. These barriers can be grouped into three categories: data-related barriers; organisational barriers; and patient-level barriers.Commonly reported data-related barriers included the risk of bias due to small sample size ,27 or unIn relation to organisational-level barriers, ,29 reporBarriers at the patient level are due to some patients misunderstanding education in relation to nail cutting and the use of dangerous tools, such as knives or razor blades . FurtherFour studies identified potentially beneficial practices in the implementation of foot care interventions. The perception of participants (staff nurses) was the most important facilitator and education sessions and support from advocates were the most common facilitators . ParticiIn this systematic review, we searched the literature for publications on interventions to describe foot care programme structure and delivery for ESKD patients receiving haemodialysis. No limitation on the year of publication was applied, as the purpose was to identify all relevant foot-related interventions or study designs (except for case reports). The systematic review was not limited to specific categories of interventions to enable optimal comparison between interventions and provide a comprehensive overview of the evidence in this important field of foot care. This study aimed to examine the factors that help or hinder successful implementation of foot care education programmes in ESKD patients receiving haemodialysis. However, we found no previously published studies that considered foot care education programmes for haemodialysis patients who are not diabetic; thus, the present systematic review examined four studies on diabetic patients receiving haemodialysis exposed to foot care education programmes from various types of intervention designs. Two review studies used a quasi-experimental design ,27, and The studies focussed on improving patient foot care knowledge and foot self-care behaviours, as well as on foot care educational interventions, including a complex intervention in which both patients and health professionals  were educated. Regarding foot examination, two studies examined healthcare professionals, with one focussing on a nurse, podiatrist and doctor  and the All these studies focussed on diabetic patients receiving haemodialysis, which is understandable because diabetic foot syndrome is one of the common complications of diabetes mellitus (DM). However, other conditions that affect the feet also require healthcare interventions. For example, adult ESKD patients receiving haemodialysis and who are not diabetic are at high risk for serious foot complications, including foot ulceration and foot amputation, and the risks of ulceration and amputation are similar to those with diabetes . ESKD isThe educational interventions were complex interventions with multiple components. The structure of patient education can take many forms and use various methods , different intervals , varying lengths of treatment and different educators . All foot care education programmes were provided by personnel trained in the research field who had health and medical science backgrounds . The benefit of this approach is the provision of quality information to older patients . Four stThe instruments that have been used to measure outcomes varied across the studies reviewed in this article. Several instruments were used to evaluate knowledge and behavioural outcomes following foot care education interventions. Most researchers used a questionnaire as their research tool. To evaluate behavioural outcomes, two studies used the NAFF Questionnaire ,29, a 29To prevent foot complications, such as ulceration and amputation, constant care and observation of potential changes in foot health are required by both patients and healthcare professionals ,27,28,29This systematic review identified several foot health interventions that are recommended for use and development, but to ensure that studies are conducted at a high methodological level, the use of rigorous scientific methods and validated instruments is encouraged strongly. Furthermore, patients’ capacity and understanding of health education also may affect the success and development of foot health interventions. However, in all these studies, educational intervention on foot self-care behaviour was not included for caregivers if their patients suffer, e.g., from retinopathy with a visual disability. Li et al.  stated tTo our knowledge, this is the first review to identify factors that act as barriers to or facilitators of implementation of foot care education programmes for patients with ESKD receiving haemodialysis. Four studies found several barriers that affected implementation of educational interventions in foot care programmes. These barriers can be grouped into three categories: data-related barriers; organisational barriers; and patient-level barriers. Commonly reported data-related barriers included the risk of bias due to small sample size ,27 or unThis review identified potentially beneficial practices in the implementation of foot care interventions. The perception of participants (staff nurses) was the most important facilitator and education sessions and support from advocates were the most common facilitators. Among the factors that act as facilitators to implementation, the researcher focussed on nurses, as they are key personnel in healthcare delivery and play a vital role in delivering and organising treatment, avoiding adverse effects and maximising productivity in health services and patient outcomes . FurtherThis is the first systematic review to examine the factors that help or hinder the successful implementation of foot care education programmes for diabetes patients receiving haemodialysis. This systematic literature review is a comprehensive examination of foot self-care knowledge and practice interventions conducted worldwide solely on diabetic patients receiving haemodialysis. This review provides important insights on diabetic patients receiving haemodialysis management and care, an area that had been ignored in the literature and interventions. The studies included within this systematic literature review provide evidence of improved knowledge and behavioural outcomes, and how these outcomes ultimately improve quality of life for diabetic patients receiving haemodialysis. One limitation of this review is that it included only four studies. The second limitation is that the researcher failed to find any previously published studies that considered foot care education programmes for haemodialysis patients who are not diabetic. Furthermore, the systematic review did not include studies that examined caregiver foot care knowledge and practices.Foot care knowledge and positive behaviours are required to prevent lower extremity complications (ulceration and amputation) for diabetes patients receiving haemodialysis and can impact health care positively if early assessment and foot care education programmes have been undertaken properly. This systematic review has provided evidence that it is possible to influence foot care knowledge and self-care behaviours in both diabetic patients receiving haemodialysis and healthcare professionals. Foot care education approaches identified in this review can be used to improve patient care. Regular foot screening and care are necessary to reduce the risk of foot ulcerations and lower-extremity amputation among ESKD patients receiving haemodialysis. Most foot care education has been implemented through lectures and individual training, contributing to positive outcomes in foot care knowledge and behaviours. Foot-related education studies will benefit from the use of a more systematic process of development and testing in the future. More research is required to promote effective foot care, particularly in those with ESKD who require haemodialysis and who are not diabetic. In the future, researchers and practitioners must implement a vigorous education programme that focusses on ESKD patients receiving haemodialysis who are not diabetic gaining access to foot self-care among the older population. Furthermore, nephrology nurses play an important role in early detection and appropriate interventions when the risk of foot ulceration is high. Thus, researchers and practitioners need to develop tools for early assessment and foot care education programmes to enable the implementation of preventive strategies for nephrology nurses.


Students, staff, and faculty in higher education are facing unprecedented challenges due to the COVID-19 pandemic. Recent data revealed that a good number of academic activities and opportunities were disrupted as a result of the COVID-19 pandemic and its variants. While much uncertainty remains for the next academic year, how higher education institutions and their students might improve responses to the rapidly changing situation matters. This systematic review and framework proposal aim to update previous empirical work and examine the current evidence for the effectiveness of growth mindset interventions in young adults. To this end, a systematic search identified 20 empirical studies involving 5, 805 young adults. These studies examined growth mindset within ecologically valid educational contexts and various content areas. Generally, these findings showed that brief messages of growth mindset can improve underrepresented students' academic performance and facilitate other relevant psychological constructs. In addition, we argue, although growth mindset has been identified as a unitary concept, it is comprised of multiple interdependent skills, such as self-control, self-efficacy, and self-esteem. Understanding the nature of growth mindset may contribute to successful mindset implementation. Therefore, this article presents a practical framework to help educators in higher education rethink the multidimensionality of growth mindset and to provide their students with alternative routes to achieve their goals. Finally, additional articles were discussed to help evaluate growth mindset interventions in higher education. Students' growth mindsets—how malleable they perceive their abilities to be—play a pivotal role in their academic achievement Dweck,  and haveCurrently, academics around the world are facing the ongoing impact of an unprecedented situation—COVID-19, which has been disrupting academic activities and in-person interactions  as opposed to fixed . This malleability of mindset has been demonstrated to encourage people to think flexibly so they are not discouraged as easily in challenging situations Dweck, . A majorIncremental implicit theories are closely associated with a growth mindset  for articles up through January 2022  related to a combination of search terms relating to growth mindset, implicit theories of intelligence, population age (college and university students), intervention , and the type of study. All articles were filtered for article type (peer-reviewed), language of study (English), and publication (non-book chapters). Database specific filters were also applied if available. These database searches initially led to 1,520 relevant abstracts, and after removing 280 duplicates, 1,240 abstracts remained. For the remaining 1,240 abstracts, the lead researchers applied the eligibility criteria to identify relevant studies. Inclusion criteria included studies that (a) used empirical designs; (b) appeared in peer-reviewed journals; (c) were available in the English language; (d) involved growth mindset as a primary or secondary variable; (e) set within a higher education/college/university context and (f) included an intervention for growth mindset. The intervention or training should have been explicitly developed in line with the incremental theory of intelligence  sample, (b) delivery, (c) intervention, (d) duration, and (e) outcome measures .We also used the previously validated Checklist to Enhance Methodological Quality in Intervention Programs .Eight studies examined the effects of growth mindset interventions on first-year undergraduate students enrolled in introductory courses . Other studies did not specify its contexts in terms of content area. There is increasing interest today in how a brief mindset intervention may contribute to outcomes other than academic achievement . It is evident that researchers in different disciplines have started to recognize the value and the need of psychological interventions in addition to regular courses in higher education. Specifically, an increasing literature has examined the effectiveness of Wise interventions (WIs), which focuses on a single construct, often drawn from diverse psychological perspectives, and target specific psychological processes  design. Participants were randomly assigned to a growth mindset intervention or a matched control group. As mentioned before, one study used quasi-experimental non-randomization . In this regard, growth mindset, or resilience in general, becomes more indispensable than ever. Institutional services and support should be implemented to help those students who have lost their usual routines and are stuck in chronic passivity to overcome barriers and succeed.As universities, colleges, and students plan and prepare for an unknown future, how might these educational institutions help students along the way to a successful career? A more positive and malleable way of interpreting our surroundings matters more than ever. While some students might have better self-regulatory skills, others do not. Therefore, higher education institutions can help their students identify additional resources, try new strategies, and seek input from others to promote resilience and their psychological needs over various stages of the pandemic. Likewise, students may use their time while learning remotely to develop the sub-abilities associated with growth mindset, so that they can maintain productivity and contribute to their institutions. Taken together, this paper hopes to summarize recent empirical findings about growth mindset interventions and conclude with practical considerations for application of the proposed framework to implement growth-mindset-related practices in higher education.The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author/s.Y-RK conceived and designed the analysis. CS performed the analysis. Y-RK and CS wrote the manuscript. Both authors contributed to the article and approved the submitted version.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflictof interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Diffuse idiopathic skeletal hyperostosis (DISH) is an ossifying and ankylosing skeletal condition that can be associated with DISH-related dysphagia in the case of cervical involvement. In contrast to most cases of dysphagia, which are managed conservatively, DISH-related dysphagia can be discouraging due to the progressive nature of DISH. We report two cases of DISH-related dysphagia that were treated with the surgical removal of osteophytes via an anterolateral approach. We were able to remove osteophytes using the bottleneck point as an anatomical landmark between the vertebral body and the bony excrescence. Patients’ symptoms improved following osteophyte removal, without recurrence. In cases of DISH-related dysphagia, osteophyte removal using an osteotome could improve dysphagia safely and quickly. Diffuse idiopathic skeletal hyperostosis (DISH), also known as Forestier disease, is an ossifying and ankylosing skeletal condition characterized by ossification of ligaments, ossification of tendons, and entheses in various regions of the body . The radCervical involvement in DISH can be either asymptomatic or associated with various symptoms, including dysphagia, dyspnea, dysphonia, foreign body sensation, hoarseness, stridor, spinal rigidity, cervical pain, and neurological signs caused by medullary compression . DysphagIn contrast to most cases of dysphagia, which are managed by conservative measurements, DISH-related dysphagia can be discouraging due to the progressive nature of DISH ,10. AlthWe report two cases of DISH-related dysphagia that were successfully treated with surgical removal of osteophytes via an anterolateral approach. We were able to remove osteophytes safely and quickly using the bottleneck point as an anatomical landmark between the vertebral body and the bony excrescence.A 64-year-old man visited the department of otolaryngology presenting with swallowing difficulty for the past 2 months. Although he was able to have an oral diet, he felt difficulty in swallowing solid food and showed severe aspiration tendency in swallowing liquid food. His medical history included atrial fibrillation and he was on digoxin. On laryngoscopic examination, a large protruding mass was identified in the posterior pharyngeal wall . LateralA 65-year-old man visited the department of otolaryngology presenting with dysphagia and odynophagia for 3 months. Although he was able to have an oral diet, he felt severe difficulty in swallowing both solid and liquid food. He complained of a 12-kilogram reduction in body weight due to difficulty swallowing. He had undergone gastrectomy for stomach cancer 13 years ago and was taking psychiatric medications for bipolar disorder. Laryngoscopic examination revealed a protruding mass at the posterior pharyngeal wall obstructing the laryngeal entrance . LateralIn the present study, we report two cases of dysphagia due to anterior osteophytes with underlying DISH. The patients were successfully treated with osteophyte removal via anterolateral approach. Based on axial images of preoperative CT, the osteophytes could be removed easily using an osteotome starting from the bottleneck point between the vertebral body and the excrescent osteophyte . This caAny disruption in the swallowing process can be defined as dysphagia . DysphagIn contrast to dysphagic patients with other medical conditions, the role of conservative treatment seems limited in patients with DISH-related dysphagia. Conservative treatments, including medical treatment , dietary measures , and pain relief , have been proposed for patients with DISH-associated dysphagia ,15,16,17Recent studies have reported excellent clinical outcomes following surgical removal of anterior osteophytes in patients with DISH-related dysphagia. Chung et al. reported that 16 of 21 patients showed an improvement in symptoms at one month postoperatively . MattiolOsteophytectomy can be performed safely and quickly using the bottleneck point between the vertebral body and the bony excrescence. The surgery took less than an hour in both patients. Although the majority of studies did not report the detailed surgical technique for osteophyte removal, most of the available studies used high-speed drills for the removal of osteophytes ,20,21. HMost previous studies reported on simple osteophytectomy via an anterolateral approach, while others have utilized cervical fusion with or without anterior plate fixation. The usefulness of cervical fusion has not yet been established; however, some advocate for performing cervical fusion to prevent late recurrence of osteophytes after surgery . AlthougIn the present study, we report two cases of DISH-related dysphagia. The anterior osteophyte was removed using an osteotome, starting from the natural bottleneck point between the vertebral body and the bony excrescence. Patients’ symptoms improved following osteophyte removal, without recurrence. In cases of DISH-related dysphagia, osteophyte removal using an osteotome could improve dysphagia safely and quickly.


Anxiety and depression are common among older adults and can intensify during perioperative periods, but few mental health interventions are designed for older surgical patients’ unique needs. We developed and adapted a perioperative mental health (PMH) bundle for older patients comprised of behavioral activation (BA) and medication optimization (MO) to ameliorate anxiety and depressive symptoms before, during, and after cardiac, orthopedic, and oncologic surgery.We used mixed-methods including workshop studios with patients, caregivers, clinicians, researchers, and interventionists; intervention refinement and reflection meetings; patient case review meetings; intervention session audio-recordings and documentation forms; and patient and caregiver semi-structured interviews. We used the results to refine our PMH bundle. We used multiple analytical approaches to report the nature of adaptations, including hybrid thematic analysis and content analysis informed by the Framework for Reporting Adaptations and Modifications – Expanded.Adaptations were categorized by content (intervention components), context , training, and evaluation. Of 51 adaptations, 43.1% involved content, 41.2% involved context, and 15.7% involved training and evaluation. Several key adaptations were noted: 1) Intervention content was tailored to patient preferences and needs . 2) Cohort-specific adaptations were recommended based on differing patient needs. 3) Compassion was identified by patients as the most important element.We identified evidence-based mental health intervention components from other settings and adapted them to the perioperative setting for older adults. Informed by mixed-methods, we created an innovative and pragmatic patient-centered intervention bundle that is acceptable, feasible, and responsive to the needs of older surgical populations. This approach allowed us to identify implementation strategies to improve the reach, scalability, and sustainability of our bundle, and can guide future patient-centered intervention adaptations. Approximately 14.4 million inpatient and 12 million major ambulatory surgeries are performed annually in the US -9. FurthPsychotherapeutic interventions, or psychological and behavioral treatments aimed at changing behaviors , have beIn addition to psychotherapy, pharmacotherapy interventions and medication-based treatments to address health conditions  show proHowever, most psychotherapeutic and pharmacotherapeutic interventions were developed for younger adults and may be less effective for older surgical patients due to differences in risks  and symWe conducted a multi-stakeholder qualitative interview study with 22 patients over age 65 who underwent major orthopedic, oncologic, or cardiac/thoracic surgeries and 18 perioperative clinicians . PatientThese challenges highlighted the need for a mental health intervention for older surgical patients to alleviate symptoms of anxiety and depression before, during, and after surgery. Both patients and clinicians voiced the need for mitigating patients’ fears and uncertainties across the perioperative care continuum, supporting both behavioral changes and psychiatric medication management, especially during the hospital stay; flexibility to address each patient’s characteristics, contexts, and surgical procedures; and, hiring a dedicated perioperative mental health interventionist  to deliver the intervention.Towards this end, we proposed incorporating psychotherapeutic and pharmacotherapeutic treatments into a perioperative mental health (PMH) intervention bundle for older surgical patients -31. Our NCT05110690)  . We defiOur work was guided by ADAPT , a frameThe study was conducted at a large academic medical center in St. Louis, Missouri, with approximately 18,000 adult inpatient surgeries annually.pre-implementation  and post-implementation . Twenty-four patients from three surgical cohorts  were enrolled in the feasibility studies. These surgical procedures were selected due to their complex nature and high risk for postoperative complications and other poor outcomes . Wem, falls  .Given that this study focuses on describing the intervention bundle adaptation process and the use of multiple methods to track these systematically, it does not include the evaluation results from the feasibility study (see protocol ). The InThis study included study partners in both pre-implementation and post-implementation phases, and participants (enrolled patients and caregivers) from the feasibility study in the post-implementation phase only.In the pre-implementation phase, we organized an internal advisory board (IAB) of study partners from the community and collaborators of the research team The IAB was comprised of patients and caregivers from each targeted surgical specialty; surgeons and nurses from each surgical specialty; community socia workers/interventionists (masters-level clinicians trained in BA and MOD); pharmacists; a health IT administrator; Barnes Jewish Hospital patient experience representatives; and research team members . Patients on our IAB have a surgical and mental health history. Patients and caregivers were recruited to the IAB through word of mouth and advertisements at the academic medical center.In the post-implementation phase, we included patient participants and caregivers from the feasibility study. Patients were at least 60 years of age, scheduled for one of the three identified surgical specialties, with clinically significant depressive or anxiety symptoms (see protocol for further details ). PatienData collection methods, participants, and findings from each method are presented in IAB workshop studios, weekly intervention refinement meetings, weekly case review meetings, and periodic intervention reflection meetings were audio-recorded and transcribed.We performed a hybrid inductive-deductive thematic analysis for each data source . First, what was being adapted and the nature of the adaptations; when did the adaptations happen; who suggested the adaptations; and why the adaptations were needed. JA and AM coded the content of each meeting in accordance with coding categories  and tallied the frequencies of FRAME-based codes, identifying the most commonly suggested types of adaptations. We conducted thematic and content analysis on weekly intervention refinement and case review meetings. Following transcription and review, JA openly coded transcripts using data-driven codes. Then, JA and another researcher (AM) determined coding categories based on the Framework for Reporting Adaptations and Modifications – Expanded (FRAME ), a framPatient and caregiver interviews were audio-recorded and transcribed for hybrid thematic analysis. A qualitative research team (JA and AM or FL) first read transcripts multiple times for familiarity, and then both openly coded transcripts using data-driven codes . Second, they identified similar and overlapping codes and factors and categorized them into sub-themes, which were compared within and across transcripts to identify higher-level themes . These higher-level themes were translated into adaptation suggestions, which were coded using FRAME, similar to how the team analyzed IAB workshop studios, with weekly intervention refinement meetings, case review meetings, and periodic intervention reflection meetings. Discrepancies in coding were resolved through discussion and consensus with the interventionist team.Audio-recordings of intervention sessions and documentation forms were analyzed for adaptations by our interventionists across patients and for fidelity to the core components of our intervention bundle. Session documentation forms completed by the perioperative wellness team were analyzed using a deductive thematic analysis approach: adaptations noted on these forms were analyzed at the patient level and then higher-level themes on adaptations across patients were organized using FRAME.(Appendix S1) developed by our interventionist team and evaluated for language and clarity by researchers (JA and KF). The fidelity rating checklist mirrored the core components of the intervention bundle. After piloting the rating checklist, an undergraduate researcher (trained by JA) listened to the audio-recordings and documented how well the interventionists were delivering the intervention bundle as intended in the standard operating procedures (SOPs) or deviating from the intervention bundle SOPs. A PhD-level social worker (KH) randomly selected 20% of these intervention session recordings and completed the fidelity rating checklist. Fidelity was rated based on four core components: personalized rationale; values and goals assessment; activity scheduling; and activity tracking. Personalized rationale and values and goals assessment were considered completed if were discussed with the participant during at least one BA session. Activity scheduling and tracking were considered complete if participants engaged in scheduling activities during at least 80% of the BA sessions after session 3 (out of a maximum of 10). The IRR was calculated between the two researchers for all items on the fidelity rating checklist .Second, the intervention bundle fidelity was assessed using a structured fidelity rating checklist Data were systematically collected between June 2021 and September 2022. 29 IAB study partners (including 15 patients and caregivers) and 19 patients and caregivers from our feasibility study participated in our adaptation assessment .Out of 51 adaptations, content adaptations represented 43.1% (n = 22), contextual adaptations 41.2% (n = 21), and training and evaluation adaptations 15.7% (n = 8). The most common nature of adaptations was tailoring/rewording/refining adaptations , while the most common level of adaptation was at the individual patient or practitioner-level . Additionally, most adaptations were based on practical considerations , were reactive , and served to increase implementation or the ability of staff to deliver the intervention bundle successfully . In the sections below, we describe these adaptations across pre- and post-implementation phases.We identified 22 content adaptations : 9 were pre-implementation (17.6%), and 13 were post-implementation (25.5%) .One example of a content-based adaptation includes renaming interventionists. During IAB Studio #2, study partners discussed intervention language and expressed that the term “perioperative wellness partner (PWP)” could better reflect the intervention bundle deliverer’s holistic training while emphasizing a comfortable environment for patients to improve their wellness after surgery. Other IAB members agreed, stressing that someone trained to speak reassuringly with patients and serve as a mental health advocate was necessary, as the patient would rely on the bond formed throughout the entire perioperative process. In a similar discussion about language and patient acceptability, the term “medication optimization and de-prescription” was refined to “medication optimization (MO).” This phrase felt less intimidating to patients, who were previously wary about stopping any of the medications they already took. This planned adaptation occurred at the target intervention group level and was intended to align the intervention bundle with organization goals better.“need for rapport building [first], so that we actually can personalize it. It's kind of… hard to personalize it when you don't know the patient that well and you're kind of working to get to know them through that.” Thus, building a relationship with the PWP was crucial and was recommended prior to beginning BA. Following further discussion, the research team decided to modify the content of the first session to focus on building trust and rapport and introducing the patient to the intervention and its core components . This planned adaptation occurred at the individual patient/practitioner level and was intended to increase the effectiveness of the intervention bundle.In another example, across IAB Studios #2 and #3, several IAB members suggested that it could be difficult for patients to connect with and trust strangers with personal issues during their first session, especially over the phone. One PWP also emphasized that there was a “Having [patients] strictly write stuff down… they don't really seem to need that.” Similarly, Cardiac-Patient-3’s documentation form noted that they did not track or schedule activities according to their PWP’s instructions but remained very active and talked to their PWP about their recovery period activities. Similarly, Orthopedic-Patient-2 voiced that they “had the same problem when [they] went through trauma therapy. [They] just don't write things down.” Orthopedic-Patient-60 declined to log their activities, so their PWP proposed that they review their calendar at each session and recall activities without writing them down. Thus, BA documentation forms were reduced in detail and emphasized meeting the patient where they were, suggesting but not requiring activity documentation, with PWPs encouraged to offer flexible methods of activity documentation . Loosening the structure of the BA documentation form was a reactive adaptation that occurred at the individual patient/practitioner level to increase patient reach, participation, and access to the intervention bundle.During a periodic intervention reflection meeting, PWPs noted that patients had difficulty following the activity scheduling and tracking documentation forms that they were assigned. One PWP, for example, stated, We identified 21 contextual adaptations : 6 were pre-implementation (11.8%) and 15 were post-implementation (29.4%) .One significant pre-implementation contextual adaptation involved forming separate teams for each intervention bundle component, as feedback indicated that the PWP would require real-time assistance during MO to correctly identify which medication changes could benefit the patient. At IAB Studios #2 and #3, patients and caregivers remarked that they wanted to see clinicians handling their medications directly rather than through consultation with ancillary staff and researchers. Several clinicians for leading MO were suggested, including primary care physicians and pharmacists. Ultimately, the research team established that the new surgical wellness program would comprise two teams: the PWP team and the pharmacy team. The PWP team managed BA and supervised all sessions, while the pharmacy team (pharmacists and a geriatric psychiatrist) managed MO. This planned addition to the intervention bundle occurred at the target intervention group level and served to increase the ability of staff to deliver MO successfully.“very sensitive… Very caring.“ They elaborated, “I feel with all my heart that [my PWP] really helped me through a tough time… and cared about… my health and my well-being.” Similarly, Oncologic-Patient-5 said, “[My PWP] wasn’t judgmental. [They were] totally understanding.” This also aligned with findings from weekly patient case review meetings, as other PWPs agreed that including elements of emotional validation and warmth was important for intervention bundle success. Thus, to maintain the standard of empathetic care, the research team opted to incorporate elements of compassion into the intervention bundle protocol, adapting each session to be more interactive and patient-sensitive. PWPs were instructed to reassure patients that their sessions were flexible and personalized for their preferences, schedules, and needs. Adding these elements to the intervention bundle was a planned adaptation at the target intervention group level and served to align the intervention bundle with organization goals.Across periodic intervention reflection meetings and interviews, PWPs and patients noted that their overall success with the intervention bundle relied heavily on building trust and warm relationships during sessions. Cardiac-Patient-1 noted that their PWP was “[Details about the intervention bundle] should be told to people before the surgery and they need to know what benefits are [and] what to do. And who to talk to for help.” Orthopedic-Patient-2 and others felt that they went into the study not fully understanding what they needed to do and how the intervention bundle would help them, and only realized partway through the study. This was also evident in our session documentation form analysis: some patients did not understand what they were supposed to do before study participation and were ultimately not interested in the intervention bundle upon finding out more details throughout sessions. For example, Orthopedic-Patient-6’s documentation form on their 5th session indicated that “the patient opted to withdraw from the study. [They] stated that this is something that doesn’t interest [them],” after two missed sessions and two sessions where they declined to complete the BA instructions. Thus, the research team modified consenting language to include a more thorough description of what to expect from the intervention bundle. This reactive adaptation on an individual patient/practitioner level served to increase reach, participation, and access to the study for patients.Additionally, patients suggested that during recruitment, before scheduling sessions, PWPs should provide more detailed explanations of the intervention bundle using more straightforward language. Cardiac-Patient-2 explained, Furthermore, we noted three key differences between surgical cohorts throughout the feasibility study: pre-operative timelines, session schedules, and patient needs. First, we observed substantial differences among the cohorts in perioperative timelines. Orthopedic patients typically scheduled their surgeries over 3 months in advance, oncologic patients scheduled their surgeries about 2 weeks in advance, and cardiac patients scheduled their surgeries about 2–3 days in advance. Therefore, orthopedic patients typically had more time preoperatively to start the intervention and plan pre-operative sessions, while cardiac patients had little pre-operative preparation time. This was noted for future implementation considerations to better shape intervention plans for each cohort.Second, differences in postoperative schedules and medical treatment were observed between cohorts, resulting in changes to session frequency. For example, oncologic patients often required continued chemotherapy and thus could not attend BA sessions as frequently; they needed sessions every 2–3 weeks (vs. 1–2 weeks). Similarly, orthopedic patients were often busy with physical therapy following surgery, resulting in sessions scheduled every 2–3 weeks.“incorporating [techniques] into the evening and the morning routine,” which benefitted them. In another example, orthopedic patients typically had a physical therapist and received exercise instructions to strengthen replacement joints. Thus, PWPs established physical goals more frequently for them.Third, each cohort had specific surgery-based needs and priorities and utilized different activities and techniques. For example, oncologic patients often had trouble sleeping due to extensive discomfort and had difficulties with physical recovery. As such, PWPs adapted their recommendations to provide sleep hygiene suggestions. Oncologic-Patient-2 explained that their PWP aided them in sleep hygiene strategies and felt that the BA components helped them with We identified 1 pre-implementation  and 7 post-implementation training and evaluation adaptations  .Before intervention bundle implementation, study partners agreed during IAB Studios #1, #2, and #3 that training interventionists were essential to obtain patient buy-in and trust in the intervention bundle. Patients were apprehensive about social workers, since they were skeptical about the potential lack of intervention training or experience in delivering mental health interventions. Thus, all PWPs recruited for this study came with training and prior experience in mental health. They were also trained in BA by Puspitasari and colleagues (using BASA training modules) . TraininWeekly intervention meetings also helped PWP and pharmacy team to review the SOPs and materials with BA and MO treatment developers and receive continuous feedback. This planned addition to the study was conducted at an individual practitioner level and increased the ability of staff to deliver the intervention bundle successfully.Several training sessions were incorporated across intervention implementation as both refreshers and to introduce new elements to the study. First, intervention lead coordinators (EL and KH) provided several refresher training sessions and materials to train all PWPs on introducing the study, introducing the intervention bundle, and working through each form with patients. Training sessions were held over four 1–2 hour video conference meetings and included a mix of didactic and interactive content . The sessions provided an orientation to the revised intervention manual and the objectives for each session, along with a review of unchanged core components and instructions on future work adaptations. This added element was planned at an individual practitioner level and was based on practical considerations to increase staff’s ability for successful intervention delivery.Another post-implementation adaptation to training involved adding pharmacy students to the pharmacy team to provide further expertise regarding medication optimization and education for patients. Training sessions were led by the two study team clinical pharmacy specialists with multiple weekly sessions. Session content included good clinical practices; review of the MO SOPs; electronic health record access and navigation; intervention database navigation; and demonstrating compassion and empathy during patient communication. Students were given supplemental readings about antidepressant dosing and potentially harmful medications. This reactive addition to study training occurred at an individual practitioner level and was based on practical considerations to increase staff’s ability for successful intervention delivery.In addition, several evaluation adaptations were made to the study as reactive responses to data and outcome collection difficulties. For example, patients were evaluated originally at 1-month, 2-month, and 3-month follow-ups. However, the 2-month follow-up was removed from the SOP due to difficulty in following up with patients. This reactive removal of an element occurred at the target intervention group level and served to increase reach, participation, and access to the study.Personalized rationale was discussed for 87% of patients (n = 20), and values and goals assessment were discussed for 78% of patients (n = 18). Only 26% of participants engaged in activity scheduling (n = 6) and 17% in activity tracking (n = 4) for at least 80% of sessions after session 3.A few patients  did not follow the core components of the intervention bundle. For example, Oncologic-Patient-2 was uninterested in BA and MO, and their sessions mainly consisted of their PWPs checking in on their recovery and activities. This content-based removal of BA and MO elements increased participation in the study but lacked fidelity to the original intervention bundle’s purpose and functions.However, most patients followed the core components of the intervention bundle while altering or skipping some BA and MO steps. For instance, Cardiac-Patient-5 did not schedule any activities, but was very motivated to recover from their procedure, so their PWP worked with them to identify goals, priorities, and strategies for meeting them. This refining of the BA SOP let the patient decide how to utilize BA in a way that worked for them. Even though they did not schedule activities, they planned to do them on their own terms throughout the week, increasing the effectiveness of the intervention bundle and adhering to its components.We reported on the systematic adaptation process of a PMH intervention bundle for older adults to ensure intervention bundle feasibility and sustainability across three different surgical settings.Our comprehensive and robust approach to adaptation led to the development and refinement of our PMH intervention bundle that we anticipate will be acceptable, appropriate, and feasible for patients and PWPs in our full trial. Using the ADAPT framework to capture process , and FRAOur data revealed differences in the types of adaptation between the pre-implementation and the post-implementation phases. In the pre-implementation phase, we reported more planned adaptations, mostly around content, to fit the intervention to the perioperative setting. In the post-implementation phase, the number of reactive content and contextual adaptations increased. Several elements  were added in the post-implementation phase. These data indicate the importance of feasibility trials to develop adaptable interventions to increase the probability of fitting evidence-based interventions in new settings and/or for new populations. Specifically, pre-implementation adaptation work has historically supported intervention-context fit and has contributed to intervention sustainability . Spendinhow to adapt and track adaptations along the process [One of the main challenges in the field of adaptation is examining  process  as the l process . We used process . While o(Appendix S2) [Our PMH intervention bundle , dubbed ndix S2) .First, activity BA scheduling and tracking forms are now flexible and based on patients’ comfort and preference in entering necessary information; for example, some patients may prefer writing their activities down in a journal, while others might note their activities in their mobile phone. Second, BA activities now depend heavily on each individual patient’s preferences and surgical recovery. Furthermore, PWPs demonstrate flexibility in scheduling and session agenda planning according to each patient’s mood during sessions. Examples of supplemental behavioral activities include activity plans for self-directed mindfulness practice, sleep hygiene exercises, and evidence-based cognitive training.Third, surgery-based protocols are adjusted according to the different priorities, pre-operative timelines, session schedules, and patient needs of each surgical cohort. For example, orthopedic patients can schedule more pre-operative sessions, while oncologic patients can schedule one or two sessions before their surgeries. Cardiac patients can either schedule one session prior to surgery or do postoperative sessions only.Fourth, our PMH intervention bundle takes on a shared decision-making approach with patients and is flexible for each patient’s needs and types of surgeries. Our data found the importance of the PWP establishing trust with their patient and assessing patient needs and preferences while approaching their situation with empathy and compassion. Our data also showed the importance of giving the patient the option of using MO to reduce problematic medications and increase sub-therapeutic doses of antidepressant medications to therapeutic levels through a collaborative approach. In the immediate postoperative period, giving the option for the PWP and pharmacy team to visit the patient in the hospital is important. Following discharge, patients can choose how to utilize BA activity scheduling and tracking to support an individualized, active recovery. Patients can also schedule more or fewer sessions depending on their physical recovery progress and level of stress.In the updated PMH intervention bundle, two main components are integrated to prepare cardiac, oncologic, and orthopedic patients for surgery and to promote enhanced recovery. MO reduces the use of problematic medications and increase sub-therapeutic doses of antidepressant medications to therapeutic levels. Through a collaborative approach, medication adjustments are made with the patient and pharmacy team. Additionally, BA engages patients in activities that are personally rewarding, supporting an individualized, active recovery from surgery, and encouraging patients to gradually re-engage in the important activities and cope with perioperative stress.The PMH intervention bundle is carried out remotely via phone or secure web conference, with optional in-person visit/s while the patient is hospitalized. Each patient is assigned a PWP, who works with the patient prior to surgery and approximately 3 months after surgery. Preoperatively, the PWP establishes trust with their patient, assessing patient needs and preferences while approaching their situation with compassion. Meanwhile, the pharmacy team assesses patient medications and discusses recommendations with the patient and inpatient care teams, ensuring any changes are maintained in-house following surgery. Within the hospital, the pharmacy team conducts MO again if any further changes needed to be made. Finally, at home post-discharge, wellness partners work with patients on BA . Further MO guidance can be provided at the patient’s request.One-on-one sessions occur on a weekly basis initially and then are reduced to every two weeks or according to the patient’s needs and preferences for a total of up to 10 sessions. Session duration is approximately 40 minutes per session but can be adjusted depending on patient needs and treatment goals.All adaptations to the intervention bundle ensure personalized perioperative mental health care delivery. Although we have made several changes, we maintain the core components of the original intervention bundle and ensure its fidelity. In other words, the underlying functions of targeting behavioral change and medication optimization remain constant, preparing older patients for surgery through BA to build resilience and through MO to improve medication regimens and reduce risk of complications.We will conduct a Hybrid Type 1 Effectiveness-Implementation RCT to assess the effectiveness and implementation-potential of our adapted PMH intervention bundle in 300 older surgical patients across cardiac, orthopedic, and oncologic cohorts. Our control condition will receive printed mental health resources from our team, while the intervention condition will receive our PMH bundle. Our primary outcome of interest is depression/anxiety. Exploratory outcomes include quality of life, medication list, delirium, length of stay, rehospitalization, falls, PMH intervention bundle reach, implementation potential , and overall patient experience.First, the approach was resource-intensive, requiring iterative data collection, analysis, and integration from several sources and stakeholders. Nevertheless, this can also be considered as a strength of the approach as it allowed us to conduct a thorough examination of necessary adaptations to suit our target surgical population’s needs, priorities, and preferences, thereby improving the rigor in our intervention adaptation process. Second, our adaptations to the bundle were informed by the needs of our participants and advisory board members who may not be representative of diverse backgrounds . However, we are currently conducting a follow-up study to investigate this particular aspect, which is supported by our Diversity, Equity, and Inclusion Community Advisory Board. Third, given that this is a single-site study, feedback gathered might not have been representative of the overall target population’s needs and preferences; additionally, results may not be generalizable from academic to community hospital settings. We plan for future multi-site evaluation that will help us refine the bundle to meet the needs of patients across both rural and urban settings.We acknowledge study limitations. Mental health symptoms are a significant issue in the perioperative setting and can worsen adverse surgical outcomes. Across the literature, several studies have reported on interventions to address perioperative depression and anxiety, but often for general adult surgical populations, not specifically older adults. Additionally, few studies have utilized mental health interventions along the entire perioperative timeline from pre-operative preparation to postoperative at-home recovery. In response to a pressing need for perioperative mental health interventions adapted for an older surgical population, we identified evidence-based mental health intervention components from other settings and adapted them to the perioperative setting for older adults in a novel study. Tracking and assessing adaptations through multiple methods, we have created a pragmatic and patient-centered intervention bundle comprised of BA and MO components that fits the needs of older surgical populations.


Vascular calcification (VC) is a growing burden in aging societies worldwide, and with a significant increase in all-cause mortality and atherosclerotic plaque rupture, it is frequently found in patients with aging, diabetes, atherosclerosis, or chronic kidney disease. However, the mechanism of VC is still not yet fully understood, and there are still no effective therapies for VC. Regarding energy metabolism factories, mitochondria play a crucial role in maintaining vascular physiology. Discoveries in past decades signifying the role of mitochondrial homeostasis in normal physiology and pathological conditions led to tremendous advances in the field of VC. Therapies targeting basic mitochondrial processes, such as energy metabolism, damage in mitochondrial DNA, or free-radical generation, hold great promise. The remarkably unexplored field of the mitochondrial process has the potential to shed light on several VC-related diseases. This review focuses on current knowledge of mitochondrial dysfunction, dynamics anomalies, oxidative stress, and how it may relate to VC onset and progression and discusses the main challenges and prerequisites for their therapeutic applications. Vascular calcification (VC) is prevalent in diabetes mellitus, atherosclerosis, and chronic kidney disease (CKD), is increasing progressively during aging, and is closely associated with many cardiovascular events and mortality , 2. ScieMitochondria are the center of energy metabolism in eukaryotic cells, participating in a variety of metabolic biochemical activities, including oxidative phosphorylation (OXPHOS), the Krebs cycle, fatty acid-oxidation, calcium management, and heme biosynthesis . MoreoveMitochondria contain multiple electron transporters that can form a broad network of producing reactive oxygen species (ROS) and antioxidant defenses. Multiple insults, including oxidative damage itself, can cause an imbalance between production and detoxification of ROS and cause oxidative damage to biomolecules, including mitochondrial DNA (mtDNA), and then induce VC . In thisVascular calcification is the process of the active deposition of calcium phosphate on the blood vessel wall under the cell-mediated process, which can be summarized in three stages as follows: (1) pro-calcification factors induce vascular smooth muscle cell (VSMC) osteogenic differentiation; (2) differentiation VSMCs release matrix vesicles; (3) matrix vesicles promote the formation of hydroxyapatite and are deposited on the blood vessel wall, ultimately promoting the onset of VC. In this study, we briefly summarized the classification and multiple mechanisms of VC.via size is unclear; it is generally believed that microcalcification refers to punctate calcifications with a diameter of <15 μm. Almost all microcalcifications can be seen in the thickened intima ; however, the specific mechanisms governing adventitia calcification are not clear. By far, ValvC is considered an aging-related degeneration disease. ValvC will lead to ventricular hypertrophy, atrial fibrillation, and heart failure  , 16. ForVascular calcification is a complex pathological process involving multiple cell types, including VSMCs, vascular endothelial cells (VECs), pericytes, and macrophages . They plVascular smooth muscle cells are the primary cell type of arterial wall, which help maintain the elasticity and contractility of blood vessels. The contractile phenotype is the primary function of normal VSMCs and exhibits low proliferative and synthetic characteristics. Although VSMCs are terminally differentiated cells, they exhibit a highly plastic phenotype . Under pNumerous factors have been identified as contributors to the VSMC osteogenic phenotype transformation, which can be considered as an imbalance between anti-calcific  and pro-calcific   22). In. In22). Vascular endothelial cells are the primary cell type in the vascular intima and build the barrier between blood and vascular wall to prevent or reduce the damage caused by harmful substances in the blood flow and play an essential role in the structural and functional integrity of arteries . VEC dysEndothelial-mesenchymal transition is the process of losing endothelial features and acquiring mesenchymal or myofibroblastic phenotypes eventually leading to cells with osteogenic potential and playing pivotal roles in VC . Deficievia BMPR2-JNK signaling pathway  and interleukin-1 beta (IL-1β) can promote VC through induced EndMT  pathway . Calcipr pathway . Moreove pathway  can reduignaling . Similarignaling .The earliest evidence that angiogenesis and ectopic calcification may be associated was revealed in the 1980s . Since tIn addition to direct differentiation to osteoblast-like cells, VECs also mediate VC by releasing calcification potential EVs under pathological conditions. The released EVs from HG stimulated VECs can induce VSMC aging and calcification through the mTOR signaling pathway .Macrophages have strong plasticity and functional heterogeneity. The primary two subsets are “the classical activated macrophage” (M1) and “the alternative activated macrophage” (M2) . ThroughMolecular imaging use co-injected with fluorescent nanoparticles to visualize macrophages (NIRF nanoparticle) and calcification (OsteoSense) study reveals macrophage accumulated in calcification area . MoreoveBasic calcium phosphate (BCP) crystals consist mainly of calcium hydroxyapatite . BCP stiPericytes are perivascular cells of mesenchymal origin found in all vascularized organs with multiple functions including vessel growth, permeability, and contractility . To datePericytes are characterized as irregular cells with ruffled edges, lack of migration into 3-D collagen gels, the existence of α-SMA, immunoreactivity with mAb 3G5, and the absence of immunoreactivity with antibodies against von Willebrand factor (vwf) were all observed , 51. PerPericyte infiltration correlates positively with VC; one hypothesis is that pericytes may be resident vascular progenitor cells found in the adventitia that have the potential to move into the media and intima of the arteries, affecting surrounding cells, and differentiate into osteoblasts when subjected to pathological stress. The RANK/RANKL/OPG signaling pathway is currently considered to be the main pathway for pericyte-mediated VC . GlucocoOrgan interactions are involved in VC . Bone-vaOsteoblast-like cells are absent in the normal arterial wall. However, in a VC-induced context, the VSMCs can differentiate into chondroblast/osteoblast-like cells . VC shar“Vascular injury response theory” is one of the critical hypotheses of AS; more importantly, endothelial injury can not only trigger the process of AS but also initiate intimal and medial calcification by releasing apoptotic bodies and matrix vesicles containing cell debris . After vLaminar flow has a vascular protective effect whereas disturbed flow exerts a harmful effect. The development of VC is also tightly regulated by mechanical stress especially on the endothelial surface (shear stress); the evidence from VC prefers to occur at branched or bifurcated areas of the vasculature, and these regions are mainly characterized by shear stress that will induce the damage of VECs; in contrast, laminar flow upregulation KLF2 and inhibition of endothelial BMP/SMAD1/5 signaling alleviate VC .When hydroxyapatite deposits on the thin fibrous cap, the local shear stress can increase by 47.5%, which significantly increases the risk of plaque rupture . CoronarExtracellular vehicles (EVs) are nano-sized lipid-bound vesicles that are released from cells into the extracellular space . Ultrastvia its trafficking function of tissue non-specific alkaline phosphatase (TNAP) to EVs that lead to high mineralization competence in the extracellular milieu  –83. As tMitochondria are highly dynamic organelles that continuously fusion and fission according to actual needs; for example, moderate exercise can enhance mitochondrial biogenesis . New mitAging and damaged mitochondria are mainly removed by mitophagy . MitophaCalcium is a critical second messenger involved in intracellular and extracellular signaling cascades and is required for vascular physiology; more importantly, studies now recognize that calcium can participate in vascular pathophysiology by interacting with ROS to regulate a series of signaling pathways .+ and Pi levels  and a light (L) strand. The 16.6 kb genome has less intergenic spacing and encodes 37 genes (13 protein-coding genes), all involved in oxidative phosphorylation; 2 rRNAs; and 22 tRNAs . In contDespite mitochondrial epigenetics being a fascinating area of research, the role of epigenetics in mitochondria still remains a controversial notion. Recent findings, however, indicate that VC is related to abnormal mtDNA methylation . PresumaPOLG that locals in mitochondria and takes charge of mtDNA replication and maintenance, leading to mitochondria having a relatively inefficient DNA repair system; as a result, mtDNA had low stability and was prone to mutation or deletion  is the only DNA polymerase encoded by the gene deletion .−/− mice deficient for the mitochondrial polymerase-γ proofreading activity (polG−/−/ApoE−/−) model. They found that POLG−/−ApoE−/− mice exhibited extensive mtDNA damage and oxidative phosphorylation defects but did not exhibit an increase in ROS. Moreover, POLG−/−ApoE−/− mice had more severe AS and VC compared with POLG+/+ApoE−/− mice; this indicates that POLG-related mtDNA damage could promote the development of AS and VC.To determine whether mtDNA damage directly promotes AS, Yu et al.  construcAnother study reported that the mutation at position 5513 from G to A of mtDNA led to multiple mitochondrial respiratory chain enzyme defects, accompanying serving calcification in the basal ganglia  and the Mitochondria are highly dynamic and are constantly undergoing fusion, fission, transport, and degradation. As mitochondria take the central role in energy metabolism, mitochondrial dynamics and bioenergetics reciprocally influence each other and play a crucial role in VC , 109. Mivia contact sites involved in cristae organization (The mitochondrion is a double-membrane-bound organelle with a smooth outer membrane (MOM) and a highly folded inner membrane (MIM) that protrudes into the mitochondrial matrix compartment (cristae) . The MIMnization . When fuvia the balance of mitochondrial synthesis and degradation. The imbalance between mitochondrial fusion and fission causes apoptosis in several pathological processes, including VC  is a critical regulator of mitochondrial fusion, and the AMPK/OPA1 pathway is linked to mitochondrial fusion and mitophagy . Throughuates VC . Corresp of Drp1 . CurrentCurrently, it is well accepted that the optimal physiological range of ROS required to maintain vascular physiology. The major source of ROS comes from mitochondria: inner membrane complexes I, II, and III , 122 andvia regulating various redox-sensitive signaling pathways -mediated superoxide production associated with enhanced coronary artery calcium (CAC)  . In animum (CAC) . Moreove in vivo .+ overload mediated by PiT-1/2, leads to oxidative stress, activates the ERK-mTOR pathway, and is critical in Pi-induced VC  nuate VC . Fibulinnuate VC .Autophagy is an important means for the maintenance of intracellular homeostasis; mitophagy is a subtype of autophagy that is considered as a protective mechanism to clear the damaged or unnecessary mitochondria, and normal mitophagy also highlights a critical role in maintaining mitochondrial biogenesis , 147. AlIt is currently known that mitophagy can alleviate VC by inhibiting phenotype transformation of VSMCs, and the possible mechanisms include the following: (1) mitophagy regulates mitochondrial biogenesis, when mitophagy is inhibited, the mass of mitochondria will be reduced significantly , and consequently impaired mitochondrial biogenesis will promote VSMC apoptosis ; (2) mitAutophagy inhibits apoptosis and necrosis by removing damaged mitochondria, and failure of autophagy can promote VC . The mitGas6/Axl-PI3K/Akt is the classic pathway in VC, and akt activation leads to downstream signaling processes involving mitochondrial apoptosis regulators, such as Bcl2 . This waPro-calcification factors such as high phosphorus lead to mitochondrial oxidative stress, which further induces VSMC apoptosis. In this process, PDK4 plays an important role, which is a critical mitochondrial matrix enzyme involved in cellular energy metabolism and may aggravate GP-induced oxidative stress and consequent VSMC apoptosis . MetformMitochondria provide almost 95% of the energy required for cell life activities . Its convia excessive oxidative stress and tightly link with glucose metabolism. ROS increases the expression of pyruvate dehydrogenase kinase 4 (PDK4), which converts oxidation to aerobic glycolysis in VSMCs  is an enzyme involved in the transport of medium and long-chain acyl-CoA out of peroxisomes . The expin vitro experiments. However, in clinical practice, there is still no specific therapy to reduce these calcifications and no evidence to support a better cardiovascular outcome with calcification reduction. Therefore, a more in-depth elucidation of the regulation mechanism and treatment progress of VC are crucial to the research of VC and the solution of clinical problems.Vascular calcification (VC) is a complex biological process that significantly increases cardiovascular and all-cause mortality. However, the pathological mechanism of VC is still unclear, and the relationship between different periods of VC and disease development is still controversial . By far,Moreover, the clinical-epidemiological features and lack of non-invasive specific diagnostic indicators, especially for microcalcification, are not well understood. VC especially coronary artery calcification (CAC) significantly increases the difficulty of percutaneous coronary intervention (PCI), and preevaluation of CAC lesions has a critical impact on subsequent treatment. Many imaging technologies have evolved in recent years to aid in the evaluation of calcified lesions, therefore, reducing the danger of intervention and improving the prognosis of surgery. These testing approaches have their own set of pros and cons, which are briefly summarized in in vivo investigations using animal models have revealed that certain medications or processes may participate in and influence the connection between mitochondrial homeostasis and VC  Further studies are needed to better understand the drivers of osteogenic phenotypic transformation and, most importantly, to characterize the spatiotemporal regulation of these drivers. (2) Are there key regulators of the transition from microcalcification to macrocalcification? (3) How to choose a treatment for calcification: Inhibit the onset of calcification? Facilitate the transition from microcalcifications to macrocalcifications? (4) Currently, it is often assumed that phenotypic changes precede calcification, but this has not been conclusively demonstrated, and the VSMC phenotypic shift may be a cellular response to the osteogenic environment. (5) Is VC an adaptive protective mechanism against pathological damage suffered by the vasculature such as atherosclerosis? (6) Development of a non-invasive diagnostic strategy for vascular microcalcifications. (7) Establishing better and more stable animal and cellular calcification models. (8) Organs or cells cross talk involved in VC. (9) Angiogenesis and VC. (10) Vascular microenvironment and VC. The road ahead is long and hard. Persist, success is in the card.ZL and QY searched and analyzed the literature. ZL wrote the manuscript. XY and JH reviewed and edited the manuscript. All authors have read and approved the final manuscript.JH Laboratory is supported by the National Natural Science Foundation of China (No. 81873651), Hunan Province Key R&D Project (2020SK2107), and Key Projects of Hunan Health and Family Planning Commission (20201901). ZL is also supported by the postgraduate Scientific Research Innovation Project of Hunan Province (CX20210917).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Given that today’s adolescents are digital front-runners, technology-based obesity prevention strategies are age-appropriate for this population. The use of remote and wireless technologies may be suitable for extending the reach and engagement of obesity prevention efforts among high-risk Hispanic youths, as this subgroup is disproportionately affected by barriers that limit participation in traditional, in-person interventions.The purpose of this scoping review was to examine the intervention and sample characteristics of technology-based obesity prevention interventions among Hispanic adolescents. We also examined feasibility criteria to assess the acceptability and appropriateness of technology-based strategies among Hispanic youths.A comprehensive search of Embase and PubMed identified 7 studies that met the inclusion criteria. Data were extracted by 2 independent reviewers.Of the 7 included studies, half  used a randomized control trial design, with equal implementation in school  and clinic  settings. Studies commonly targeted improvements in diet  and physical activity , with only 1 (14%) study focused on sedentary behaviors. Just 2 (29%) studies reported the use of behavioral theories or models. Studies focused primarily on youths in early  or middle  adolescence, and there was limited information reported on socioeconomic status. Only 3 (43%) study conducted formative work, and few  reported on acceptability. Only 1 (14%) study reported that materials were available in Spanish and English, and only 1 (14%) study used culturally tailored content. Additionally, 3 (43%) studies used strategies that considered social determinants of health.To increase our understanding of the feasibility and effectiveness of technology-based obesity prevention strategies among Hispanic adolescents, there is a need for more feasibility studies that are theoretically grounded and comprehensively report on feasibility-related outcomes. Future studies should also leverage technology to simultaneously address multiple health behaviors beyond diet and physical activity. The result of this review can be used to guide the development of future technology-based obesity prevention strategies among Hispanic adolescents.CliniclaTrials.gov NCT04953442; https://clinicaltrials.gov/ct2/show/NCT04953442 Lifestyle interventions that promote healthy diet and physical activity habits are the cornerstone for obesity prevention among adults and youths . HoweverTechnology-based interventions use digital devices, such as computers, tablets, smartphones, and wearable devices, to deliver personalized and real-time health promotion and disease prevention interventions -13. GiveTechnology-based health promotion and disease prevention strategies are also recommended as being age-appropriate for adolescents . AdolescThe purpose of this scoping review was to systematically examine the current state of the science on technology-based obesity prevention interventions among Hispanic adolescents. This review will provide descriptive information regarding the intervention and sample characteristics with a focus on feasibility criteria including formative work, measures of acceptability, and adaptations made for SDoH and cultural considerations. The focus on feasibility criteria will provide meaningful information on the appropriateness of technology-based intervention components and targets among Hispanic youths with obesity. Following an extensive review of the literature, we will summarize findings, identify knowledge gaps, and highlight next steps for future research among this population.This scoping review was conducted using the 5-stage methodological framework for scoping studies developed by Arksey and O’Malley . In accoThe following research questions guided this review: (1) What approaches were used to develop technology-based obesity prevention interventions among Hispanic adolescents? (2) What are the intervention and sample characteristics of technology-based prevention interventions implemented among Hispanic adolescents? and (3) Were outcomes regarding the feasibility of technology-based obesity prevention interventions among Hispanic youths reported in a feasibility or pilot study or earlier in the development of a fully powered trial? Given that few technology-based interventions have been developed for Hispanic youths, studies that have applied technology-based strategies among this population are primarily still in the pre-efficacy phase, and the feasibility of intervention components has yet to be confirmed . To addrStudies identified as relevant to this scoping review were defined as empirical, peer-reviewed articles that described a technology-based obesity prevention intervention among Hispanic adolescents with obesity. A literature search of PubMed was conducted using a combination of the following Medical Subject Headings terms: obesity, adolescent, Hispanic, and intervention. The search strategy and combination of terms that were used are provided in Studies were selected using the following eligibility criteria: (1) included adolescents aged 13-18 years; (2) focused on obesity prevention or included a lifestyle intervention focused on reducing obesity outcomes  and cardiometabolic disease risk factors ; (3) written in English, (4) used a technology-based component; (5) conducted within the United States, given that Hispanic adolescents in this country have a unique sociocultural and environmental context; and (6) included a sample of at least 50% of participants who self-identify as Hispanic/Latino. This criterion has been used in previous reviews to ensure that studies are focused on Hispanic adolescents and that study findings are applicable to this population -34. We dOnce relevant articles were selected, information from all studies was extracted using a narrative review approach . We deveDescriptive statistics  were calculated for intervention and sample characteristics as well as feasibility-related components. A content analysis approach was used to summarize patterns found in the information extracted across data extraction categories . Data syThe search yielded a total of 20,160 results, with 10,512 remaining after duplicates were removed. The Consolidated Standards of Reporting Trials (CONSORT) diagram in Participant characteristics are presented in Feasibility-related characteristics are presented in Technology-based interventions are a promising, age-appropriate, and accessible approach for engaging high-risk youths in disease prevention efforts; however, few such interventions have been developed and tested specifically for Hispanic youths. This scoping review used rigorous methods to review technology-based obesity prevention interventions among Hispanic adolescents. This review examined intervention and sample characteristics. Strengths in intervention and sample characteristics include the use of a rigorous randomized controlled trial study designs among half of all studies, although only 2 reported that they were fully powered. Most studies assessed physical activity, diet, anthropometrics, cardiometabolic biomarkers, and a psychosocial outcome. Although the focus of a scoping review is not on study outcomes, it is worth noting that studies that reported significant improvements to anthropometric or cardiometabolic outcomes used a hybrid approach of in-person and remote technology strategies and reported high acceptability and retention (≥80%) ,40,42. AThis review also focused on the reporting of feasibility-related outcomes in each study. Only a few studies reported on technical issues, and it is not clear if this is because few technical issues were experienced or if the investigators did not publish this information. Of the studies that did publish on acceptability, they reported very high levels of satisfaction and enjoyment. Attrition, another indicator of engagement and feasibility, was mixed, with some studies reporting high levels of attrition. Taken together, reporting on feasibility criteria across studies in this review are limited, and although the technology-based strategies used in these interventions are promising, there is a greater need for the testing and publishing of feasibility-related criteria. To increase the feasibility, reach, and begin to move toward efficacy, there are substantial gaps that future technology-based prevention strategies should address.Only 2 studies in this review reported the use of behavioral theories and models ,37. ThesTo assess the acceptability and appropriateness of technology-based strategies among Hispanic adolescents, we examined the reporting of feasibility-related criteria including formative work, measures of acceptability, and adaptations for SDoH or cultural considerations. Just half of studies conducted formative work -38, whicLastly, similar to previously published reviews of obesity prevention interventions ,46, we fThis study focused on a high-risk population that is traditionally underrepresented in research. This review will contribute to the limited body of research describing technology-based obesity prevention interventions among Hispanic youths with obesity. Additional strengths included a rigorous, comprehensive search strategy across numerous databases and a systematic, in-depth data extraction process that was performed in duplicate to ensure reliability. Some studies may have had information missing across data extraction categories  given that they were feasibility and pilot studies. We did not assess intervention effectiveness or quality, which may be seen as a limitation; however, a more rigorous assessment of outcomes is more in line with a systematic review and not a scoping review. Lastly, the results of this study may be influenced by the search terms that were used, the use of US-based search engines, the number of databases searched, the focus on English-language articles, and the selection of databases used in the search. As a result, this review may be subject to publication bias.The literature on technology-based obesity prevention efforts among Hispanic adolescents is limited, making it difficult to determine the feasibility of this promising approach among this population. In addition to greater testing and reporting on feasibility-related outcomes, this review highlights 3 key gaps that should be addressed in future studies. There is a need for technology-based obesity prevention interventions that are theoretically grounded and that evaluate theoretical constructs to identify the underlying mechanism by which these strategies impact obesity-related outcomes and health behaviors among high-risk youths. There is a need for interventions that are tailored to the context of Hispanic youths and a need for increased evaluation and reporting of feasibility-related outcomes of these interventions to determine the acceptability and appropriateness of technology-based strategies for Hispanic youths. Furthermore, given known disparities in screen time and sleep among Hispanic youths, intervention strategies among this population should leverage technology to address a broader range of health behaviors, including sedentary behaviors and sleep, to increase program effectiveness. Addressing these gaps in future work will guide the development and implementation of technology-based obesity prevention efforts that aim to reduce obesity disparities and promote health equity among Hispanic adolescents.