Coronary Microvascular Dysfunction: A Guide for Clinicians.

Dysfunction of the coronary microvasculature has become increasingly recognized as an important mechanism of myocardial ischemia in patients without obstructive coronary artery disease. The causes and management of coronary microvascular dysfunction remain poorly understood and is still largely based on extrapolation of epicardial coronary artery disease data. Quantification of myocardial blood flow and flow reserve have improved diagnosis, though important questions remain In this review, we explain current understanding of the spectrum of pathophysiology of coronary microvascular dysfunction, summarize current diagnostic techniques to assess for coronary microvascular dysfunction, and appraise the limited data on management options specifically for patients with coronary microvascular dysfunction.

Prospective validation of clinical deterioration predictive models prior to intensive care unit transfer among patients admitted to acute care cardiology wards.

Very few predictive models have been externally validated in a prospective cohort following the implementation of an artificial intelligence analytic system. This type of real-world validation is critically important due to the risk of data drift, or changes in data definitions or clinical practices over time, that could impact model performance in contemporaneous real-world cohorts. In this work, we report the model performance of a predictive analytics tool developed before COVID-19 and demonstrate model performance during the COVID-19 pandemic. The analytic system (CoMETⓇ, Nihon Kohden Digital Health Solutions LLC, Irvine, CA) was implemented in a randomized controlled trial that enrolled 10,422 patient visits in a 1:1 display-on display-off design. The CoMET scores were calculated for all patients but only displayed in the display-on arm. Only the control/display-off group is reported here because the scores could not alter care patterns. Of the 5184 visits in the display-off arm, 311 experienced clinical deterioration and care escalation, resulting in transfer to the intensive care unit (ICU), primarily due to respiratory distress. The model performance of CoMET was assessed based on areas under the receiver operating characteristic curve, which ranged from 0.725 to 0.737. The models were well-calibrated, and there were dynamic increases in the model scores in the hours preceding the clinical deterioration events. A hypothetical alerting strategy based on a rise in score and duration of the rise would have had good performance, with a positive predictive value more than 10-fold the event rate. We conclude that predictive statistical models developed five years before study initiation had good model performance despite the passage of time and the impact of the COVID-19 pandemic. .

An Analysis of Participant Preferences Regarding Virtual Versus In-person Format of Orthopaedic Surgery Educational Materials in Low- and Middle-Income Countries.

INTRODUCTION: The University of California, San Francisco Institute for Global Orthopaedics and Traumatology Surgical Management and Reconstructive Training (SMART) course has instructed orthopaedic surgeons from low-resource countries on soft-tissue reconstruction. Before the COVID-19 pandemic, the course was conducted in-person; however, it was transitioned to a virtual format during the pandemic. The aim of this study was to determine participant preferences regarding a virtual or in-person SMART course format. METHODS: Survey data were collected via e-mail after each SMART course using RedCap or Qualtrics. Statistical analyses were conducted using Stata. RESULTS: There were 247 survey respondents from 44 countries representing all world regions, with Africa (125, 51%) the most represented. Of those who attended both an in-person and virtual course, most (82%) preferred the in-person format. In addition, all measured course outcomes were significantly better for participants attending the in-person course. The most common reason for not attending an in-person course was the cost of travel (38, 51%). DISCUSSION: This study demonstrated a preference toward in-person learning for the SMART course. In addition, those surgeons participating in the in-person course endorsed increased positive outcomes from the course. Increased emphasis should be placed on in-person surgical skills training for low-resource surgeons.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and Radiolabeled Leukocyte SPECT/CT Imaging for the Evaluation of Cardiovascular Infection in the Multimodality Context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations From ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

Total-Body PET/CT Applications in Cardiovascular Diseases: A Perspective Document of the SNMMI Cardiovascular Council.

Digital PET/CT systems with a long axial field of view have become available and are emerging as the current state of the art. These new camera systems provide wider anatomic coverage, leading to major increases in system sensitivity. Preliminary results have demonstrated improvements in image quality and quantification, as well as substantial advantages in tracer kinetic modeling from dynamic imaging. These systems also potentially allow for low-dose examinations and major reductions in acquisition time. Thereby, they hold great promise to improve PET-based interrogation of cardiac physiology and biology. Additionally, the whole-body coverage enables simultaneous assessment of multiple organs and the large vascular structures of the body, opening new opportunities for imaging systemic mechanisms, disorders, or treatments and their interactions with the cardiovascular system as a whole. The aim of this perspective document is to debate the potential applications, challenges, opportunities, and remaining challenges of applying PET/CT with a long axial field of view to the field of cardiovascular disease.

Best Practices for Developing International Academic Partnerships in Orthopaedics.

ABSTRACT: Traumatic and nontraumatic orthopaedic conditions are major contributors to global morbidity and account for the majority of life-years lived with disability worldwide. Additionally, the burden of musculoskeletal injuries has increased substantially over the past 3 decades. Unfortunately, in low and middle-income countries (LMICs), access to orthopaedic care is limited, leading to a disproportionate burden of disease. The Lancet Commission on Global Surgery has emphasized the urgent need for unified international commitment and research collaboration to achieve universal access to safe and affordable surgical care. However, conducting high-quality orthopaedic research in LMICs remains challenging as a result of disparities in training, access to resources, infrastructure, and equipment availability. Partnerships between high-income countries (HICs) and LMICs have emerged in recent decades as an effective approach to combatting some of these challenges. These partnerships aim to bridge the gaps by facilitating collaborative research and knowledge exchange. The establishment of successful partnerships requires a collaborative and reciprocal approach that starts with a clear understanding of mutual research aims and the availability of resources. Despite the potential benefits, various factors can make establishing such partnerships difficult. However, these partnerships can have a substantial impact in delivering quality orthopaedic education and research training, thus improving access to care in resource-limited environments. This paper represents the collaborative effort of multiple international academic orthopaedic surgeons with extensive experience in HIC-LMIC partnerships. Our aims were to outline the best practices for conducting orthopaedic research within these relationships and to provide guidance for future successful collaborations.

Moral foundations and HPV vaccine acceptance in the United States: State, parental, and individual factors.

RATIONALE: Appeals to intuitive morality may present a novel approach to addressing vaccine hesitancy. OBJECTIVE: To better understand the relationship between morality and vaccination by employing Moral Foundations Theory to studies surrounding the HPV vaccination at multiple different levels of decision making. METHOD: We employed three different study modalities which examined moralities link to vaccination by employing Moral Foundations Theory. A state-wide ecological study aimed to understand population level trends. Two randomized control interventional studies were then created to understand the effects of Moral Foundations Theory based interventions on both parents of children and individual decision makers. RESULTS: We demonstrated a negative association at the state level between the purity moral foundations and HPV vaccination rates (ß = -.75, SE 0.23; p < .01) and a positive association between loyalty and HPV vaccination rates (ß = 0.62 SE 0.24; p < .05). The parental study built upon this by demonstrating negative association between higher moral purity scores and attitudes towards the HPV vaccine and intention to vaccinate their children (ß = -0.27 SE 0.07; p < .001). Our final study demonstrated a Moral Foundations Theory based intervention was associated with an increase in the odds of indicating an intention to receive the HPV vaccination (adjusted Odds Ratio (aOR) 2.59, 95% Confidence Interval (CI) 1.62-4.14). This equates to a 20% increase in the predicted probability of the intention to receive an HPV vaccine (39% CI (36%-42%) vs 60% CI (57%-63%). CONCLUSIONS: Together, these studies demonstrate that moral foundations, specifically the purity foundation, appear to have a strong and consistent relationship with HPV vaccination. They also demonstrate the how moral values-based interventions may serve as a novel approach to increase HPV vaccine uptake with potential to be employed to target vaccine hesitancy more broadly.

A pilot, masked, randomized controlled trial to evaluate local gentamicin versus saline in open tibial fractures (pGO-Tibia).

Background: Open tibial fractures have a high risk of infection that can lead to severe morbidity. Antibiotics administered locally at the site of the open wound are a potentially effective preventive measure, but there are limited data evaluating aminoglycoside antibiotics. The objective of this study was to assess the feasibility of a clinical trial to test the efficacy of local gentamicin in reducing the risk of fracture-related infection after open tibial fracture. Methods: This study is a single-center, pilot, masked, randomized controlled trial conducted at the Muhimbili Orthopaedic Institute. Participants were randomized intraoperatively after wound closure to receive gentamicin solution or normal saline solution injected at the fracture site. Follow-ups were completed at 2 weeks, 6 weeks, 3 months, 6 months, 9 months, and 1 year postoperatively. The primary feasibility outcomes were the rate of enrollment and retention. The primary clinical outcome was the occurrence of fracture-related infection. Results: Of 199 patients screened, 100 eligible patients were successfully enrolled and randomized over 9 months (11.1 patients/month). Complete data were recorded at baseline and follow-up for >95% of cases. The rate of follow-up at 6 weeks, 3 months, 6 months, 9 months, and 1 year were 70%, 68%, 69%, 61%, and 80%, respectively. There was no difference in adverse events or any of the measured primary and secondary outcomes. Conclusion: This pilot study is among the first to evaluate locally administered gentamicin in open tibial fractures. Results indicate a rigorous clinical trial with acceptable rates of enrollment and follow-up to address this topic is possible in this setting.

Deciphering data: How should clinical trials change your clinical practice?

INTRODUCTION: The careful consideration of how to apply findings from the scientific literature is important to every physician's clinical practice. This can pose a difficult task, particularly with the increasing speed of technological advances and complexity involved in modern clinical trials. This review introduces a new method, the WHOM criteria (Who, How, Outcomes, Minimizing bias), from which orthopedic surgeons and other physicians can efficiently evaluate novel medical literature for inclusion into their clinical practice. WHOM CRITERIA: The WHOM framework consists of four steps. The first step, Who, involves confirming whether a sample population studied is similar to one's patient under treatment, in order to ensure the results can be reasonably applied. Second, the How, comprises evaluating the intervention performed and ensuring that it could be reasonably replicated. The third step requires thoroughly evaluating the outcomes used in the study so as to ensure they are clinically meaningful to both the treating physician and the patient. Finally, there must be a careful evaluation of potential sources of bias and the ways in which errors and bias were minimized in all phases of the study. CONCLUSION: Evidence-based practice should drive clinical decision making whenever the necessary literature is available. This requires the careful evaluation of new literature on a regular basis so that physicians can render safe and effective health care in partnership with their patients. The WHOM criteria are described in order to aid clinicians in navigating published research and change practice when appropriate.

GO-Tibia: a masked, randomized control trial evaluating gentamicin versus saline in open tibia fractures.

BACKGROUND: The rate of open tibia fractures is rapidly increasing across the globe due to a recent rise in road traffic accidents, predominantly in low- and low-middle-income countries. These injuries are orthopedic emergencies associated with infection rates as high as 40% despite the use of systemic antibiotics and surgical debridement. The use of local antibiotics has shown some promise in reducing the burden of infection in these injuries due to increasing local tissue availability; however, no trial has yet been appropriately powered to evaluate for definitive evidence and the majority of current studies have taken place in a high-resource countries where resources and the bio-burden may be different. METHODS: This is a prospective randomized, masked, placebo-controlled superiority trial designed to evaluate the efficacy of locally administered gentamicin versus placebo in the prevention of fracture-related infection in adults (age > 18 years) with primarily closeable Gustillo-Anderson class I, II, and IIIA open tibia fractures. Eight hundred ninety patients will be randomized to receive an injection of either gentamicin (treatment group) or saline (control group) at the site of their primarily closed open fracture. The primary outcome will be the occurrence of a fracture-related infection occurring during the course of the 12-month follow-up. DISCUSSION: This study will definitively assess the effectiveness of local gentamicin for the prevention of fracture-related infections in adults with open tibia fractures in Tanzania. The results of this study have the potential to demonstrate a low-cost, widely available intervention for the reduction of infection in open tibia fractures. TRIAL REGISTRATION: Clinicaltrials.gov NCT05157126. Registered on December 14, 2021.

The Dimeglio Olecranon Method Is Reliable in Diverse, Contemporary Patients for Predicting Future Growth.

BACKGROUND: Growth assessment, which relies on a combination of radiographic and clinical markers, is an integral part of clinical decision-making in pediatric orthopaedics. The aim of this study is to evaluate the accuracy and reliability of the Diméglio skeletal age system using a modern cohort of pediatric patients. METHODS: A retrospective review was undertaken of all patients at a large tertiary pediatric hospital who had lateral forearm radiographs (before the age of 14 y for females and before 16 y for males). In addition, all of these patients had height measurements within 60 days of their forearm x-ray and a final height listed in their medical records. The x-rays were graded by 5 reviewers according to the Diméglio skeletal age system. Inter and intraobserver reliability was tested. RESULTS: One hundred forty-seven patients with complete radiographs and height data were evaluated by 5 observers ranging in experience from medical students to senior pediatric orthopaedic surgeons. The Diméglio system demonstrated excellent reliability across levels of training with an intraobserver correlation coefficient of 0.995 (95% CI, 0.991-0.997) and an interobserver correlation coefficient of 0.906 (95% CI, 0.857-0.943). When the Diméglio stage was paired with age and sex in a multivariable linear regression model predicting the percent of final height, the adjusted R2 was 78.7% (model P value <0.001), suggesting a strong relationship between the Diméglio stage (plus age and sex) and percent of final height. CONCLUSION: This unique approach to maturity assessment demonstrates that the Diméglio staging system can be used effectively in a modern, diverse patient population. LEVEL OF EVIDENCE: Level II; retrospective cohort study.

Beyond prediction: Off-target uses of artificial intelligence-based predictive analytics in a learning health system.

Introduction: Artificial-intelligence (AI)-based predictive analytics provide new opportunities to leverage rich sources of continuous data to improve patient care through early warning of the risk of clinical deterioration and improved situational awareness.Part of the success of predictive analytic implementation relies on integration of the analytic within complex clinical workflows. Pharmaceutical interventions have off-target uses where a drug indication has not been formally studied for a different indication but has potential for clinical benefit. An analog has not been described in the context of AI-based predictive analytics, that is, when a predictive analytic has been trained on one outcome of interest but is used for additional applications in clinical practice. Methods: In this manuscript we present three clinical vignettes describing off-target use of AI-based predictive analytics that evolved organically through real-world practice. Results: Off-target uses included:real-time feedback about treatment effectiveness, indication of readiness to discharge, and indication of the acuity of a hospital unit. Conclusion: Such practice fits well with the learning health system goals to continuously integrate data and experience to provide.