An RGDKGE-Containing Cryptic Collagen Fragment Regulates Phosphorylation of Large Tumor Suppressor Kinase-1 and Controls Ovarian Tumor Growth by a Yes-Associated Protein-Dependent Mechanism.

The growth and spread of malignant tumors, such as ovarian carcinomas, are governed in part by complex interconnected signaling cascades occurring between stromal and tumor cells. These reciprocal cross-talk signaling networks operating within the local tissue microenvironment may enhance malignant tumor progression. Understanding how novel bioactive molecules generated within the tumor microenvironment regulate signaling pathways in distinct cellular compartments is critical for the development of more effective treatment paradigms. Herein, we provide evidence that blocking cellular interactions with an RGDKGE-containing collagen peptide that selectively binds integrin ß3 on ovarian tumor cells enhances the phosphorylation of the hippo effector kinase large tumor suppressor kinase-1 and reduces nuclear accumulation of yes-associated protein and its target gene c-Myc. Selectively targeting this RGDKGE-containing collagen fragment inhibited ovarian tumor growth and the development of ascites fluid in vivo. These findings suggest that this bioactive collagen fragment may represent a previously unknown regulator of the hippo effector kinase large tumor suppressor kinase-1 and regulate ovarian tumor growth by a yes-associated protein-dependent mechanism. Taken together, these data not only provide new mechanistic insight into how a unique collagen fragment may regulate ovarian cancer, but in addition may help provide a useful new alternative strategy to control ovarian tumor progression based on selectively disrupting a previously unappreciated signaling cascade.

Hip Resurfacing: A Single Surgeon U.S. Series With Minimum Ten-Year Follow-up.

BACKGROUND: Metal-on-metal hip resurfacing is an alternative to total hip arthroplasty (THA). The aim of this study was to determine implant survivorship, analyze patient-reported outcomes measures and to determine patient satisfaction for patients who underwent metal-on-metal hip resurfacing at a large US academic institution by a single surgeon with a minimum of 10-year follow-up. METHODS: Patients who underwent hip resurfacing from September 2006 through November 2009 were included. Patient demographics and variables were collected from a prospectively maintained institutional database and patients completed an additional questionnaire with patient-reported outcomes measures. RESULTS: A total of 350 patients (389 hips) out of 371 (433 hips) with a minimum 10-year follow-up were successfully contacted (94.3% follow-up). Mean age was 53 years, 258 were male (73%). 377 out of 389 hips (96.9%) did not require additional surgery. Gender was significantly related to implant survivorship (males 99.0%, females 90.9%; P < .001). 330 patients (369 hips, 94.8%) were satisfied with their surgery. Males had higher proportion of satisfaction scores (P = .02) and higher modified Harris Hip Score (odds ratio = 2.63 (1.39, 4.98), P = .003). Median modified Harris Hip Score score for non-revised hips was 84.0 [80.0; 86.0] versus those requiring revision, 81.5 [74.0; 83.0], (P = .009). CONCLUSION: At a minimum 10-year follow-up, hip resurfacing, using an implant with a good track record, demonstrates 99.0% survivorship in male patients with an average age of 52 years. We believe that the continued use of metal-on-metal hip resurfacing arthroplasty in this population is justified by both positive patient reported outcomes and survivorship.

Prevalence of PErioperAtive CHildhood obesitY in children undergoing general anaesthesia in the UK: a prospective, multicentre, observational cohort study.

BACKGROUND: Childhood obesity has become a serious global healthcare challenge. No UK data currently define its anaesthetic and perioperative implications. We aimed to determine obesity prevalence amongst UK children undergoing general anaesthesia and the incidence of predefined adverse perioperative events, and to compare perioperative obesity rates with National Child Measurement Programme (NCMP) data. METHODS: During a site-selected consecutive 7-day study period, all children (2-16 yr) undergoing general anaesthesia were included. Anonymised hospital, surgical, and procedural details; demographic data; and adverse perioperative events were collected prospectively by Paediatric Anaesthesia Trainee Research Network (PATRN) collaborators. RESULTS: For this study, 102 UK hospitals participated and 4232 cases were included in the final analysis; 76% of hospitals did not routinely calculate BMI. In addition, 3030 (71.6%; 95% confidence interval [CI]: 70.2-73.0%) children of healthy weight were compared with 537 (12.7%; 11.7-13.7%) children who were overweight and 478 (11.3%; 10.3-12.2%) children with obesity. Children with obesity (n=71; 14.9%) more commonly underwent (adeno)tonsillectomy than children of healthy weight (n=282; 9.3%; P<0.001; odds ratio [OR] 2.15; 95% CI: 1.58-2.92). Fewer children with obesity (n=365; 77% vs n=2552; 85%) were anaesthetised by consultant anaesthetists (OR 0.62; 95% CI: 0.48-0.79). Mask ventilation was difficult for 3.7% of children with obesity vs 0.6% of children of healthy weight (difference 3.0%; 95% CI: 1.3-4.7%; P<0.001). Comparison with NCMP data demonstrated an over-representation of obesity amongst the paediatric surgical population. CONCLUSIONS: This large multicentre cohort study suggests a concerning prevalence of children with obesity presenting for anaesthesia. These results should be used to inform optimal provision of care for this population and support perioperative healthcare initiatives to address the burden of childhood obesity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03994419.

Telehealth in cancer care: during and beyond the COVID-19 pandemic.

The COVID-19 pandemic has precipitated the rapid uptake of telehealth in cancer care and in other fields. Many of the changes made in routine clinical practice could be embedded beyond the duration of the pandemic. This is intended as a practical guide to cancer clinicians and others in establishing and improving the quality of consultations performed by telehealth.

The Potential Effects of Imposing a Body Mass Index Threshold on Patient-Reported Outcomes After Total Knee Arthroplasty.

BACKGROUND: Operative eligibility thresholds based on body mass index (BMI) alone may risk restricting access to improved pain control, function, and quality of life. This study evaluated the use of BMI-cutoffs to offering TKA in avoiding: 1) 90-day readmission, 2) one-year mortality, and 3) failure to achieve clinically important one-year PROMS improvement (MCID). METHODS: A total of 4126 primary elective unilateral TKA patients from 2015 to 2018 were prospectively collected. For specific BMI(kg/m2) cutoffs: 30, 35, 40, 45, and 50, the positive predictive value (PPV) for 90-day readmission, one-year mortality, and failure to achieve one-year MCID were calculated. The number of patients denied complication-free postoperative courses per averted adverse outcome/failed improvement was estimated. RESULTS: Rates of 90-day readmission and one-year mortality were similar across BMI categories (P > .05, each). PPVs for preventing 90-day readmission and one-year mortality were low across all models of BMI cutoffs. The highest PPV for 90-day readmission and one-year mortality was detected at cutoffs of 45 (6.4%) and 40 (0.87%), respectively. BMI cutoff of 40 would deny 18 patients 90-day readmission-free, and 194 patients one-year mortality-free postoperative courses for each averted 90-day readmission/one-year mortality. Such cutoff would also deny 11 patients an MCID per avoided failure. Implementing BMI thresholds alone did not influence the rate of improvements in KOOS-PS, KRQOL, or VR-12. CONCLUSION: Utilizing BMI cutoffs as the sole determinants of TKA ineligibility may deny patients complication-free postoperative courses and clinically important improvements. Shared decision-making supported by predictive tools may aid in balancing the potential benefit TKA offers to obese patients with the potentially increased complication risk and cost of care provision.

Cryptic collagen elements as signaling hubs in the regulation of tumor growth and metastasis.

Structural remodeling of the extracellular matrix is a well-established process associated with tumor growth and metastasis. Tumor and stromal cells that compose the tumor mass function cooperatively to promote the malignant phenotype in part by physically interacting with intact and structurally altered matrix proteins. To this end, collagen represents the most abundant component of the extracellular matrix and is known to control the behavior of histologically distinct tumor types as well as a diversity of stromal cells. Although a significant molecular understanding has been established concerning how cellular interactions with intact collagen govern signaling pathways that control tumor progression, considerably less is known concerning how interactions with cryptic or hidden regions within remodeled collagen may selectively alter signaling cascades, or whether inhibition of these cryptic signaling pathways may represent clinically effective therapeutic strategies. Here, we review the emerging evidence concerning the possible mechanisms for the selective generation of cryptic or hidden elements within collagen and their potential cell surface receptors that may facilitate signal transduction. We discuss the concept that cellular communication links between cell surface receptors and these cryptic collagen elements may serve as functional signaling hubs that coordinate multiple signaling pathways operating within both tumor and stromal cells. Finally, we provide examples to help illustrate the possibility that direct targeting of these unique cryptic signaling hubs may lead to the development of more effective therapeutic strategies to control tumor growth and metastasis.

The safety profile and effectiveness of propofol-remifentanil mixtures for total intravenous anesthesia in children.

BACKGROUND: Total intravenous anesthesia is used in less than 10% of operations in the UK. Many pediatric anesthetists in the UK and Ireland administer total intravenous anesthesia to children using a mixture of propofol and remifentanil in the same syringe. This unlicensed drug has not been studied clinically, because of lack of Medicines and Healthcare products Regulatory Agency (UK) or Food and Drug Administration (US) approval to undertake such studies. AIM: The aim of this service evaluation was to assess the safety profile and effectiveness of propofol-remifentanil mixtures in the pediatric population undergoing a variety of surgical procedures. METHODS: Pediatric Anesthetists in the UK and Ireland who regularly used propofol-remifentanil mixtures for total intravenous anesthesia were invited to submit data. This data were analyzed to assess the effectiveness of anesthesia and the incidence and nature of any complications that occurred. RESULTS: Usable data were collected from 873 patients. Mixtures were most commonly administered in gastroenterology and ear, nose, and throat procedures. Two-thirds of patients were less than 10 years old, and their mean weight was 28.7 kg. Anesthesia using the mixture alone was successful in all but 3 patients. The commonest nonserious complication was coughing (4.6%), followed by movement (3.3%). The overall incidence of serious, related, unexpected adverse events requiring intervention was 1.7%. These included desaturation (5 patients), apnea (3), abdominal/chest rigidity (2), cough requiring paralysis (2), ventilatory problems (2), and hypotension (1). Most occurred at induction, were attributable to the properties of the drugs being administered and not directly related to the use of the mixture. No life-threatening adverse events were recorded. Complications were less common if a ≤5 µg mL-1 concentration of remifentanil was used. CONCLUSION: These data demonstrate that effective anesthesia can be administered to pediatric patients undergoing a wide range of procedures using mixtures of propofol and remifentanil. Serious, related, unexpected adverse events requiring intervention had a low incidence and were largely due to predictable effects of the drugs being administered. A ≤5 µg mL-1 remifentanil concentration is associated with proportionately less complications.

Callus culture as a new approach for the production of high added value compounds in Ilex paraguariensis: genotype influence, medium optimization and compounds identification.

Ilex paraguariensis (yerba mate) is a native species from South America and is a rich source of bioactive compounds. There is a lack of research efforts on the phytochemical investigation of callus culture from this species. In the present study, an effort was made to optimize callus culture conditions and to identify secondary compounds. Calli were induced from 10 genotypes using leaf explants and the best genotype was selected to evaluate the effects of cytokinin types and concentrations on callus induction and biomass accumulation. The best genotype and cytokinin treatment were used to conduct one last experiment with sucrose concentrations in culture media and its effects on calli biomass, antioxidant activity and secondary compounds accumulation. Callus initiation was genotype dependent, and the 6-156-6 line had the best response. Zeatin supplemented medium showed higher callus induction rate (82%) and higher biomass accumulation after 120 days (328.2 mg). Higher biomass and secondary compounds accumulation were observed for calli on 3% sucrose medium. Antioxidant activity was not affected by sucrose concentrations. Yerba mate callus culture allowed the accumulation of chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, theobromine and caffeine.

How Are We Measuring Cost-Effectiveness in Total Joint Arthroplasty Studies? Systematic Review of the Literature.

BACKGROUND: As volumes of total hip arthroplasty (THA) and total knee arthroplasty (TKA) continue to rise, it is important to understand their economic impact. No systematic review on cost-effectiveness of THA/TKA has been performed since 2016 despite recent changes in the healthcare environment. The purpose of the study is to provide a contemporary analysis of the cost-effectiveness of total joint arthroplasty and the use of quality-adjusted life years (QALYs). METHODS: A systematic review was performed from 2005 to 2020. Online databases (OVID Medline, PubMed, Cost-Effectiveness Analysis Registry, Google Scholar, Elton B. Stephens Co) were queried to identify economic analyses that evaluated the cost-effectiveness of THA/TKA. RESULTS: In total, 38 studies met the screening criteria. Study designs were primarily Markov models (68%), cohort studies (16%), and randomized trials (8%). Most studies adopted either a societal perspective (45%) or a health system perspective (39%). Analysis revealed that THA/TKA was strongly cost-effective compared to nonsurgical treatment. THA/TKA procedures that were not delayed were more cost-effective than delayed intervention. The majority of studies used QALYs as the primary quality metric (82%); in all these studies there was a significant improvement in QALYs gained. CONCLUSION: Given the high economic impact of arthroplasty, ongoing assessment of cost-effectiveness is needed. Twenty-four percent of studies included in this systematic review were published in the last 4 years of this 15-year study period, highlighting the need for continuous assessment of aggregate data. Future studies should incorporate the cost-effectiveness of THA and TKA with respect to the work-value provided by surgeon providers to support health policy and reimbursement.

Lessons from Exploring Chemical Space and Chemical Diversity of Propolis Components.

Propolis is a natural resinous material produced by bees and has been used in folk medicines since ancient times. Due to it possessing a broad spectrum of biological activities, it has gained significant scientific and commercial interest over the last two decades. As a result of searching 122 publications reported up to the end of 2019, we assembled a unique compound database consisting of 578 components isolated from both honey bee propolis and stingless bee propolis, and analyzed the chemical space and chemical diversity of these compounds. The results demonstrated that both honey bee propolis and stingless bee propolis are valuable sources for pharmaceutical and nutraceutical development.

n-3 PUFAs improve erythrocyte fatty acid profile in patients with small AAA: a randomized controlled trial.

Abdominal aortic aneurysm (AAA) is an important cause of death in older adults, which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyte fatty acid content in 43 AAA patients (diameter 3.0-4.5 cm) and 52 healthy controls. In addition, the effect of omega-3 PUFA (n-3 PUFA) supplementation on erythrocyte fatty acid content was examined in a cohort of 30 AAA patients as part of a 12 week randomized placebo-controlled clinical trial. Blood analyses identified associations between AAA and decreased linoleic acid (LA), and AAA and increased Δ6-desaturase activity and biosynthesis of arachidonic acid (AA) from LA. Omega-3 PUFA supplementation (1.5 g DHA + 0.3 g EPA/day) decreased red blood cell distribution width (14.8 ± 0.4% to 13.8 ± 0.2%; P = 0.003) and levels of pro-inflammatory n-6 PUFAs (AA, 12.46 ± 0.23% to 10.14 ± 0.3%, P < 0.001; adrenic acid, 2.12 ± 0.13% to 1.23 ± 0.09%; P < 0.001). In addition, Δ-4 desaturase activity increased (DHA/docosapentaenoic acid ratio, 1.85 ± 0.14 to 3.93 ± 0.17; P < 0.001) and elongase 2/5 activity decreased (adrenic acid/AA ratio, 0.17 ± 0.01 to 0.12 ± 0.01; P < 0.01) following supplementation. The findings suggest that n-3 PUFAs improve fatty acid profiles and ameliorate factors associated with inflammation in AAA patients.

The HU177 Collagen Epitope Controls Melanoma Cell Migration and Experimental Metastasis by a CDK5/YAP-Dependent Mechanism.

Stromal components not only help form the structure of neoplasms such as melanomas, but they also functionally contribute to their malignant phenotype. Thus, uncovering signaling pathways that integrate the behavior of both tumor and stromal cells may provide unique opportunities for the development of more effective strategies to control tumor progression. In this regard, extracellular matrix-mediated signaling plays a role in coordinating the behavior of both tumor and stromal cells. Here, evidence is provided that targeting a cryptic region of the extracellular matrix protein collagen (HU177 epitope) inhibits melanoma tumor growth and metastasis and reduces angiogenesis and the accumulation of α-SMA-expressing stromal cell in these tumors. The current study suggests that the ability of the HU177 epitope to control melanoma cell migration and metastasis depends on the transcriptional coactivator Yes-associated protein (YAP). Melanoma cell interactions with the HU177 epitope promoted nuclear accumulation of YAP by a cyclin-dependent kinase-5-associated mechanism. These findings provide new insights into the mechanism by which the anti-HU177 antibody inhibits metastasis, and uncovers an unknown signaling pathway by which the HU177 epitope selectively reprograms melanoma cells by regulating nuclear localization of YAP. This study helps to define a potential new therapeutic strategy to control melanoma tumor growth and metastasis that might be used alone or in combination with other therapeutics.

Nutritional quality of almond, canarium, cashew and pistachio and their oil photooxidative stability.

Daily consumption of nuts is recommended as a part of a healthy diet as they contain protein and are rich in beneficial fatty acids and essential nutrients. The nutritional qualities of nuts are affected by their fatty acid composition and other factors such as maturity. Oil oxidative stability is important to determine nut nutritional quality in terms of fatty acid composition over storage. Therefore, this study aimed to (a) assess the nutritional quality (photooxidative stability and nutrient composition) of almond, cashew, pistachio and canarium (a newly commercialised indigenous nut); and (b) explore differences in nutrient concentrations between immature and mature canarium nuts. A decrease in polyunsaturated fats after photooxidation in almond and pistachio was observed. Canarium oil did not change following photooxidation suggesting canarium may display a long shelf life when stored appropriately. Our study indicated that almond provided over 50% of the recommended daily intake for manganese whereas canarium intake provided 50% of the recommended daily intake for iron (for males). Pistachio was richer in potassium compared with other nuts and canarium was richer in boron, iron and zinc than other nut species. Mature canarium kernels were richer in boron, iron and zinc but contained less potassium than immature canarium. Therefore, the current study recommended to store kernels in dark to decrease oil photooxidation, and maturity of canarium kernels at the harvest time was important affecting nutrient concentrations of kernels.

Consensus guidelines for the use and interpretation of angiogenesis assays.

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.

Adsorption and Leachable Contamination of Flucloxacillin, Cyclosporin and Amiodarone Following Delivery Through an Intravenous Administration Set.

PURPOSE: Interactions between a pharmaceutical drug and its delivery device can result in changes in drug concentration and leachable contamination. Flucloxacillin, amiodarone and cyclosporin were investigated for drug concentration changes and leachable contamination after delivery through an intravenous administration set. METHODS: Flucloxacillin, amiodarone and cyclosporin were delivered through an intravenous administration set and the eluate analysed by HPLC-UV and HPLC-MS. RESULTS: The average recovery of flucloxacillin was 99.7% and no leachable compounds were identified. The average recovery of cyclosporin was 96.1%, which contrasts previous findings that have reported up to 50% loss of cyclosporin. This is likely due to the use of DEHP-free administration sets in this study, as adsorption of cyclosporin is linearly related to DEHP content. The average recovery of amiodarone was 91.5%. 5-hydroxymethylfurfural was identified in the amiodarone solution following delivery through the administration set as well as the 5% glucose solution used for delivery. CONCLUSIONS: Drug/administration set interactions may modify pharmaceuticals during delivery. In this study, only 90% of the amiodarone was delivered through a generic administration set. Given the growing use of generic administration sets in hospital settings, validation of the suitability of their use is required to ensure patient safety and expected levels of efficacy.

Looking to tomorrow's healthcare today: a participatory health perspective.

Health systems around the world face the issue of financial and workforce sustainability. Mobile health technologies - those devices which connect health professionals, patients, payers and the many other contributors who make up the health system offer some solutions - not just as 'add ons' but as enablers of real system change. This paper presents a vision for what the health system of the future could be like and emphasises the opportunities for real patient participation in clinical decision-making if the professions can engage the technologies and patients/community in a meaningful way. Predicting the future is never easy but many of the technologies are here now - but how we will use them to make the system more patient friendly, more productive and sustainable is still for discussion. This paper should start that conversation.

EVOLVE: The Australian Rheumatology Association's 'top five' list of investigations and interventions doctors and patients should question.

BACKGROUND: The EVOLVE (evaluating evidence, enhancing efficiencies) initiative aims to drive safer, higher-quality patient care through identifying and reducing low-value practices. AIMS: To determine the Australian Rheumatology Association's (ARA) 'top five' list of low-value practices. METHODS: A working group comprising 19 rheumatologists and three trainees compiled a preliminary list. Items were retained if there was strong evidence of low value and there was high or increasing clinical use and/or increasing cost. All ARA members (356 rheumatologists and 72 trainees) were invited to indicate their 'top five' list from a list of 12-items through SurveyMonkey in December 2015 (reminder February 2016). RESULTS: A total of 179 rheumatologists (50.3%) and 19 trainees (26.4%) responded. The top five list (percentage of rheumatologists, including item in their top five list) was: Do not perform arthroscopy with lavage and/or debridement for symptomatic osteoarthritis of the knee nor partial meniscectomy for a degenerate meniscal tear (73.2%); Do not order anti-nuclear antibody (ANA) testing without symptoms and/or signs suggestive of a systemic rheumatic disease (56.4%); Do not undertake imaging for low back pain for patients without indications of an underlying serious condition (50.8%); Do not use ultrasound guidance to perform injections into the subacromial space as it provides no additional benefit in comparison to landmark-guided injection (50.3%) and Do not order anti-double-stranded DNA antibodies in ANA negative patients unless the clinical suspicion of systemic lupus erythematosus remains high (45.3%). CONCLUSIONS: This list is intended to increase awareness among rheumatologists, other clinicians and patients about commonly used low-value practices that should be questioned.

The Global Spine Care Initiative: resources to implement a spine care program.

PURPOSE: The purpose of this report is to describe the development of a list of resources necessary to implement a model of care for the management of spine-related concerns anywhere in the world, but especially in underserved communities and low- and middle-income countries. METHODS: Contents from the Global Spine Care Initiative (GSCI) Classification System and GSCI care pathway papers provided a foundation for the resources list. A seed document was developed that included resources for spine care that could be delivered in primary, secondary and tertiary settings, as well as resources needed for self-care and community-based settings for a wide variety of spine concerns (e.g., back and neck pain, deformity, spine injury, neurological conditions, pathology and spinal diseases). An iterative expert consensus process was used using electronic surveys. RESULTS: Thirty-five experts completed the process. An iterative consensus process was used through an electronic survey. A consensus was reached after two rounds. The checklist of resources included the following categories: healthcare provider knowledge and skills, materials and equipment, human resources, facilities and infrastructure. The list identifies resources needed to implement a spine care program in any community, which are based upon spine care needs. CONCLUSION: To our knowledge, this is the first international and interprofessional attempt to develop a list of resources needed to deliver care in an evidence-based care pathway for the management of people presenting with spine-related concerns. This resource list needs to be field tested in a variety of communities with different resource capacities to verify its utility. These slides can be retrieved under Electronic Supplementary Material.

The Global Spine Care Initiative: model of care and implementation.

PURPOSE: Spine-related disorders are a leading cause of global disability and are a burden on society and to public health. Currently, there is no comprehensive, evidence-based model of care for spine-related disorders, which includes back and neck pain, deformity, spine injury, neurological conditions, spinal diseases, and pathology, that could be applied in global health care settings. The purposes of this paper are to propose: (1) principles to transform the delivery of spine care; (2) an evidence-based model that could be applied globally; and (3) implementation suggestions. METHODS: The Global Spine Care Initiative (GSCI) meetings and literature reviews were synthesized into a seed document and distributed to spine care experts. After three rounds of a modified Delphi process, all participants reached consensus on the final model of care and implementation steps. RESULTS: Sixty-six experts representing 24 countries participated. The GSCI model of care has eight core principles: person-centered, people-centered, biopsychosocial, proactive, evidence-based, integrative, collaborative, and self-sustaining. The model of care includes a classification system and care pathway, levels of care, and a focus on the patient's journey. The six steps for implementation are initiation and preparation; assessment of the current situation; planning and designing solutions; implementation; assessment and evaluation of program; and sustain program and scale up. CONCLUSION: The GSCI proposes an evidence-based, practical, sustainable, and scalable model of care representing eight core principles with a six-step implementation plan. The aim of this model is to help transform spine care globally, especially in low- and middle-income countries and underserved communities. These slides can be retrieved under Electronic Supplementary Material.