Bone marrow aspirate and bone marrow aspirate concentrate: Does the literature support use in long-bone nonunion and provide new insights into mechanism of action?

PURPOSE: To assess the use of bone marrow aspirate (BM) and bone marrow aspirate concentrate (BMAC) in the treatment of long-bone nonunion and to understand mechanism of action. METHODS: A systematic review of PubMed and EBSCOHost was completed to identify studies that investigated the use of BM or BMAC for the diagnosis of delayed union and/or nonunion of long-bone fractures. Studies of isolated bone marrow-mesenchymal stem cells (BM-MSCs) and use in non-long-bone fractures were excluded. Statistical analysis was confounded by heterogeneous fracture fixation methods, treatment history, and scaffold use. RESULTS: Our initial search yielded 430 publications, which was screened down to 25 studies. Successful treatment in aseptic nonunion was reported at 79-100% (BM) and 50-100% (BMAC). Septic nonunion rates were slightly better at 73-100% (BM) and 83.3-100% (BMAC). 18/24 studies report union rates > 80%. One study reports successful treatment of septic nonunion with BMAC and no antibiotics. A separate study reported a significant reduction in autograft reinfection rate when combined with BMAC (P = 0.009). Major adverse events include two deep infections at injection site and one case of heterotopic ossification. Most studies note transient mild donor site discomfort and potential injection site discomfort attributed to needle size. CONCLUSION: The current literature pertaining to use of BM/BMAC for nonunion is extremely heterogeneous in terms of patient population and concomitant treatment modalities. While results are promising for use of BM/BMAC with other gold standard treatment methodologies, the literature requires additional Level I data to clarify the impact of role BM/BMAC in treating nonunion when used alone and in combination with other modalities. LEVEL OF EVIDENCE: Level III.

Editorial Commentary: ChatGPT Has the Potential to Be an Important Patient Education Tool and May Outperform Google.

With the growing popularity of artificial intelligence, more patients will begin to turn to chatbots such as ChatGPT for medical information. Recent research has shown that ChatGPT and Google can both provide accurate responses to numeric-based questions; ChatGPT bases its answers on more trustworthy, academic sources than Google, and the 2 tools have little overlap when queried to generate a list of frequently asked questions. Patients should use ChatGPT cautiously. The chatbot can struggle to generate appropriate responses to questions regarding patient-specific factors. Fortunately, many institutions offer evidence-based websites that provide quality information. However, if these sites do not address a specific patient's question, ChatGPT has the potential to be a powerful tool. Of importance, unlike Google, ChatGPT consistently provides patients with a reminder that they should follow up with a licensed medical provider to address their questions and concerns related to a topic.

ChatGPT Responses to Common Questions About Slipped Capital Femoral Epiphysis: A Reliable Resource for Parents?

BACKGROUND: We sought to evaluate the ability of ChatGPT, an AI-powered online chatbot, to answer frequently asked questions (FAQs) regarding slipped capital femoral epiphysis (SCFE). METHODS: Seven FAQs regarding SCFE were presented to ChatGPT. Initial responses were recorded and compared with evidence-based literature and reputable online resources. Responses were subjectively rated as "excellent response requiring no further clarification," "satisfactory response requiring minimal clarification," "satisfactory response requiring moderate clarification," or "unsatisfactory response requiring substantial clarification." RESULTS: ChatGPT was frequently able to provide satisfactory responses that required only minimal clarification. One response received an excellent rating and required no further clarification, while only 1 response from ChatGPT was rated unsatisfactory and required substantial clarification. CONCLUSIONS: ChatGPT is able to frequently provide satisfactory responses to FAQs regarding SCFE while appropriately reiterating the importance of always consulting a medical professional.

ChatGPT Responses to Common Questions About Anterior Cruciate Ligament Reconstruction Are Frequently Satisfactory.

PURPOSE: To evaluate ChatGPT responses to common questions patients have regarding anterior cruciate ligament (ACL) reconstruction. METHODS: Ten frequently asked questions regarding ACL tears and ACL reconstruction were chosen from the frequently asked questions found on the websites of major institutions. These were presented to ChatGPT and responses were rated as "excellent response not requiring clarification," "satisfactory requiring minimal clarification," "satisfactory requiring moderate clarification," or "unsatisfactory requiring substantial clarification." RESULTS: Four responses were satisfactory, requiring minimal clarification, 3 were satisfactory, requiring moderate clarification, 2 were unsatisfactory, and 1 was excellent, requiring no clarification. CONCLUSIONS: As hypothesized, ChatGPT provided generally accurate information to common questions around ACL reconstruction. Although clarification often was needed, responses were satisfactory for providing generalized information about ACL tears and ACL reconstruction. CLINICAL RELEVANCE: ChatGPT is a promising avenue for patients to learn about general background information regarding ACL reconstruction, although questions specific to any planned operation need to be addressed directly with an orthopaedic provider.

Double trouble: combined cardiovascular effects of particulate matter exposure and coronavirus disease 2019.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly grown into a pandemic. According to initial reports, the lungs were thought to be the primary target, but recent case studies have shown its reach can extend to other organs including the heart and blood vessels. The severity of cardiac complications of COVID-19 depends on multiple underlying factors, with air pollutant exposure being one of them, as reported by several recent studies. Airborne particulate matter (PM) attracts heightened attention due to its implication in various diseases, especially respiratory and cardiovascular diseases. Inhaled PM not only carries microorganisms inside the body but also elicits local and systemic inflammatory responses resulting in altering the host's immunity and increasing susceptibility to infection. Previous and recent studies have documented that PM acts as a 'carrier' for the virus and aids in spreading viral infections. This review presents the mechanisms and effects of viral entry and how pollution can potentially modulate pathophysiological processes in the heart. We aimed to concisely summarize studies examining cardiovascular outcomes in COVID-19 patients and postulate on how PM can influence these outcomes. We have also reviewed evidence on the use of renin-angiotensin system inhibitors, namely angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, in patients with COVID-19. The interplay of pollution and SARS-CoV-2 is essential to understanding the effects of accentuated cardiovascular effects of COVID-19 and deserves in-depth experimental investigations.

Exercise does not ameliorate cardiac dysfunction in obese mice exposed to fine particulate matter.

BACKGROUND: Studies have demonstrated that exposure to fine particulate matter (PM2.5) is linked to cardiovascular disease (CVD), which is exacerbated in patients with pre-existing conditions such as obesity. In the present study, we examined cardiac function of obese mice exposed to PM2.5 and determined if mild exercise affected cardiac function. METHODS: Obese mice (ob/ob) (leptin deficient, C57BL/6J background) were exposed to either filtered air (FA) or PM2.5 at an average concentration of 32 µg/m3 for 6 h/day, 5 days/week for 9 months. Following exposure, mice were divided into four groups: (1) FA sedentary, (2) FA treadmill exercise, (3) PM2.5 sedentary, and (4) PM2.5 treadmill exercise and all mice were analyzed after 8 weeks of exercise training. RESULTS: Echocardiography showed increased left ventricular end systolic (LVESd) and diastolic (LVEDd) diameters in PM2.5 sedentary mice compared to FA sedentary mice. There was increased expression of ICAM1, VCAM and CRP markers in sedentary PM2.5 mice compared to FA mice. Both FA and PM2.5 exercised mice showed decreased posterior wall thickness in systole compared to FA sedentary mice, coupled with altered expression of inflammatory markers following exercise. CONCLUSION: Obese mice exposed to PM2.5 for 9 months showed cardiac dysfunction, which was not improved following mild exercise training.

Getting to the Heart of Alzheimer Disease.

In a somewhat narrow diagnostic lens, Alzheimer disease (AD) has been considered a brain-specific disease characterized by the presence of Aß (ß-amyloid) plaques and tau neural fibrillary tangles and neural inflammation; these pathologies lead to neuronal death and consequently clinical symptoms, such as memory loss, confusion, and impaired cognitive function. However, for decades, researchers have noticed a link between various cardiovascular abnormalities and AD-such as heart failure, coronary artery disease, atrial fibrillation, and vasculopathy. A considerable volume of work has pointed at this head to heart connection, focusing mainly on associations between cerebral hypoperfusion and neuronal degradation. However, new evidence of a possible systemic or metastatic profile to AD calls for further analysis of this connection. Aß aggregations-biochemically and structurally akin to those found in the typical AD pathology-are now known to be present in the hearts of individuals with idiopathic dilated cardiomyopathy, as well as the hearts of patients with AD. These findings suggest a potential systemic profile of proteinopathies and a new hypothesis for the link between peripheral and central symptoms of heart failure and AD. Herein, we provide an overview of the cardiovascular links to Alzheimer disease.

Preconception Exposure to Fine Particulate Matter Leads to Cardiac Dysfunction in Adult Male Offspring.

Background Particulate matter (particles < 2.5 µm [ PM 2.5]) exposure during the in utero and postnatal developmental periods causes cardiac dysfunction during adulthood. Here, we investigated the potential priming effects of preconception exposure of PM 2.5 on cardiac function in adult offspring. Methods and Results Male and female friend leukemia virus b (FVB) mice were exposed to either filtered air ( FA ) or PM 2.5 at an average concentration of 38.58 µg/m3 for 6 hours/day, 5 days/week for 3 months. Mice were then crossbred into 2 groups: (1)  FA male× FA female (both parents were exposed to FA preconception) and, (2) PM 2.5male× PM 2.5female (both parents were exposed to PM 2.5 preconception). Male offspring were divided: (1) preconception FA (offspring born to FA exposed parents) and, (2) preconception PM 2.5 (offspring born to PM 2.5 exposed parents) and analyzed at 3 months of age. Echocardiography identified increased left ventricular end systolic volume and reduced posterior wall thickness, reduced %fractional shortening and %ejection fraction in preconception PM 2.5 offspring. Cardiomyocytes isolated from preconception PM 2.5 offspring showed reduced %peak shortening, -dL/dT, TPS 90 and slower calcium reuptake (tau). Gene and protein expression revealed modifications in markers of inflammation ( IL -6, IL -15, TNF α, NF қB, CRP , CD 26E, CD 26P, intercellular adhesion molecule 1, and monocyte chemoattractant protein-1) profibrosis (collagen type III alpha 1 chain), oxidative stress ( NOS 2), antioxidants (Nrf2, SOD , catalase), Ca2+ regulatory proteins ( SERCA 2a, p- PLN , NCX ), and epigenetic regulators (Dnmt1, Dnmt3a, Dnmt3b, Sirt1, and Sirt2) in preconception PM 2.5 offspring. Conclusions Preconception exposure to PM 2.5 results in global cardiac dysfunction in adult offspring, suggesting that abnormalities during development are not limited to the prenatal or postnatal periods but can also be determined before conception.

Cardiac pathophysiology in response to environmental stress: a current review.

PURPOSE: Environmental stressors are disturbing our ecosystem at an accelerating rate. An increasingly relevant stressor are air pollutants, whose levels are increasing worldwide with threats to human health. These air pollutants are associated with increased mortality and morbidity from cardiovascular diseases. In this review we discuss environmental stressors focusing mainly on the various types of air pollutants, their short-term and long-term cardiovascular effects, and providing the epidemiological evidence associated with adverse cardiovascular outcomes. Direct and indirect pathophysiological mechanisms are also linked with cardiovascular complications such as thrombosis, fibrinolysis, hypertension, ischemic heart diseases and arrhythmias. RESULTS: Evidence to date suggests that humans are constantly being exposed to unhealthy levels of environmental toxicants with the potential of serious health conditions. Environmental stressors adversely affect the cardiovascular system and pose an increased risk for cardiovascular diseases for those who reside in highly polluted areas. CONCLUSION: People with existing risk factors and those with established cardiovascular disease have increased susceptibility to environmental stressors. The literature reviewed in this article thus support public health policies aimed at reducing pollutant exposure to benefit public health.

PM2.5 exposure in utero contributes to neonatal cardiac dysfunction in mice.

OBJECTIVE: Exposure of fine particulate matter (PM2.5) to pregnant dams has been shown to be strongly associated with adverse cardiovascular outcomes in offspring at adulthood, however, effects evident during neonatal periods are unclear. We designed this study to examine cardiac function of neonatal mice (14 days old) exposed to in utero PM2.5. METHODS: Pregnant FVB female mice were exposed either to filtered air (FA) or PM2.5 at an average concentration of 91.78 µg/m3 for 6 h/day, 5 days/wk (similar to exposure in a large industrial area) throughout the gestation period (21 days). After birth, animals were analyzed at day 14 of life. RESULTS: Fourteen day old mice exposed to PM2.5 during the in utero period demonstrated decreased fractional shortening (%FS, 41.1 ± 1.2% FA, 33.7 ± 1.2% PM2.5, p < 0.01) and LVEDd (2.87 ± 0.08 mm FA, 2.58 ± 0.07 mm PM2.5, p < 0.05) compared to FA exposed mice. Contractile kinetics and calcium transients in isolated cardiomyocytes from PM2.5 exposed mice illustrated reduced peak shortening (%PS, 16.7 ± 0.5% FA, 14.7 ± 0.4% PM2.5, p < 0.01), negative contractile velocity (-dL/dT, -6.91 ± 0.3 µm/s FA, -5.46 ± 0.2 µm/s PM2.5, p < 0.001), increased time to relaxation 90% (TR90, 0.07 ± 0.003 s FA, 0.08 ± 0.004 s PM2.5, p < 0.05), decreased calcium transient amplitude (Δ340/380, 33.8 ± 3.4 FA, 29.5 ± 2.8 p.m.2.5) and slower fluorescence decay rate (τ, 0.72 ± 0.1 s FA, 1.16 ± 0.15 s PM2.5, p < 0.05). Immunoblotting studies demonstrated alterations in expression of Ca2+ handling proteins- SERCA-2A, p-PLN, NCX and CaV1.2 in hearts of 14 day old in utero PM2.5 exposed mice compared to FA exposed hearts. CONCLUSION: PM2.5 exposure during the critical in utero period adversely affects the developing mouse fetus leading to functional cardiac changes that were evident during the very early (14 days) stages of adolescence. These data demonstrated that exposure to PM2.5 during the gestation period significantly impacts cardiovascular outcomes early in life.