Prevalence and Clinical Impact of Incidental Findings on Preoperative 3D Planning Computed Tomography for Total Shoulder Arthroplasty.

INTRODUCTION: 3D planning software for shoulder arthroplasty recently emerged for aiding in intraoperative determination of native glenoid. These protocols often require increased scan resolution, however, raising the question of an increased prevalence and clinical impact of incidental findings (IFs) from preoperative imaging. METHODS: A retrospective review of preoperative shoulder CT reports was conducted for 333 consecutive patients planning anatomic or reverse total shoulder arthroplasties. Patients with thin-sliced CT scans (1.25 mm) were compared with those with standard CT scans (2.5 mm). Poisson regression was performed with baseline characteristics and potentially pathologic IFs (PPIFs). RESULTS: IFs were present in 131 of the 333 scans (39.3%), and 38 of the 333 scans (11.4%) included PPIFs. Only 8 of the 333 scans (2.4%) required workup, with 2 of the 333 (0.6%) leading to new cancer diagnoses. Thin-sliced CT scans detected a higher mean number of IFs (1.12 versus 0.22, P < 0.001) while the mean number of PPIFs remained similar (0.13 versus 0.10, P = 0.43). CONCLUSION: IFs are frequent; however, only 0.6% scans led to new cancer diagnoses. Comparison of thin-sliced with standard CT scans revealed a higher frequency of IFs but similar PPIFs, indicating increased burden of IFs without the benefit of identifying additional malignancies. As demand rises for shoulder arthroplasties, surgeons should consider the potential hidden costs of IFs when using 3D planning programs.

Spontaneous Coronary Artery Dissection in the Setting of COVID-19 Pandemic-Related Stressors: A Case Report.

Spontaneous coronary artery dissection (SCAD) is an uncommon but important cause of acute myocardial infarction, particularly in younger women and in patients with underlying fibromuscular dysplasia (FMD). There is increasing literature on patients with SCAD reporting significant emotional stress, particularly stress related to unemployment, in the week prior to their cardiac event, and emotional triggers appear to be associated with worse in-hospital and follow-up cardiac events. Additionally, the COVID-19 pandemic has resulted in significant societal stressors and increased unemployment, which have been associated with increased cardiovascular morbidity. Here, we present a case of a female presenting with an acute MI secondary to SCAD in the setting of recently learning of impending unemployment due to COVID-19 vaccine refusal. This case highlights the importance of considering SCAD in patients with significant recent emotional stress who present with MI. Additionally, in light of the emotional stressors of the COVID-19 pandemic, clinicians must be aware of the consequences significant emotional stress plays on the development of adverse complications of chronic disease.

Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis.

With the increasing prevalence of type 2 diabetes and fatty liver disease, there is still an unmet need to better treat hyperglycemia and hyperlipidemia. Here, we identify isthmin-1 (Ism1) as an adipokine and one that has a dual role in increasing adipose glucose uptake while suppressing hepatic lipid synthesis. Ism1 ablation results in impaired glucose tolerance, reduced adipose glucose uptake, and reduced insulin sensitivity, demonstrating an endogenous function for Ism1 in glucose regulation. Mechanistically, Ism1 activates a PI3K-AKT signaling pathway independently of the insulin and insulin-like growth factor receptors. Notably, while the glucoregulatory function is shared with insulin, Ism1 counteracts lipid accumulation in the liver by switching hepatocytes from a lipogenic to a protein synthesis state. Furthermore, therapeutic dosing of recombinant Ism1 improves diabetes in diet-induced obese mice and ameliorates hepatic steatosis in a diet-induced fatty liver mouse model. These findings uncover an unexpected, bioactive protein hormone that might have simultaneous therapeutic potential for diabetes and fatty liver disease.

The modern reverse shoulder arthroplasty and an updated systematic review for each complication: part II.

BACKGROUND: Globally, reverse shoulder arthroplasty (RSA) has moved away from the Grammont design to modern prosthesis designs. The purpose of this study was to provide a focused, updated systematic review for each of the most common complications of RSA by limiting each search to publications after 2010. In this part II, the following were examined: (1) instability, (2) humerus/glenoid fracture, (3) acromial/scapular spine fractures (AF/SSF), and (4) problems/miscellaneous. METHODS: Four separate PubMed database searches were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Overall, 137 studies for instability, 94 for humerus/glenoid fracture, 120 for AF/SSF, and 74 for problems/miscellaneous were included in each review, respectively. Univariate analysis was performed with chi-square and Fisher exact tests. RESULTS: The Grammont design had a higher instability rate vs. all other designs combined (4.0%, 1.3%; P < .001), and the onlay humerus design had a lower rate than the lateralized glenoid design (0.9%, 2.0%; P = .02). The rate for intraoperative humerus fracture was 1.8%; intraoperative glenoid fracture, 0.3%; postoperative humerus fracture, 1.2%; and postoperative glenoid fracture, 0.1%. The rate of AF/SSF was 2.6% (371/14235). The rate for complex regional pain syndrome was 0.4%; deltoid injury, 0.1%; hematoma, 0.3%; and heterotopic ossification, 0.8%. CONCLUSIONS: Focused systematic reviews of recent literature with a large volume of shoulders demonstrate that using non-Grammont modern prosthesis designs, complications including instability, intraoperative humerus and glenoid fractures, and hematoma are significantly reduced compared with previous studies. As the indications continue to expand for RSA, it is imperative to accurately track the rate and types of complications in order to justify its cost and increased indications.

The modern reverse shoulder arthroplasty and an updated systematic review for each complication: part I.

BACKGROUND: Globally, reverse shoulder arthroplasty (RSA) has moved away from the Grammont design to modern prosthesis designs. The purpose of this 2-part study was to systematically review each of the most common complications of RSA, limiting each search to publications in 2010 or later. In this part (part I), we examined (1) scapular notching (SN), (2) periprosthetic infection (PJI), (3) mechanical failure (glenoid or humeral component), and (4) neurologic injury (NI). METHODS: Four separate PubMed database searches were performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Overall, 113 studies on SN, 62 on PJI, 34 on mechanical failure, and 48 on NI were included in our reviews. Univariate analysis was performed with the χ2 or Fisher exact test. RESULTS: The Grammont design had a higher SN rate vs. all other designs combined (42.5% vs. 12.3%, P < .001). The onlay humeral design had a lower rate than the lateralized glenoid design (10.5% vs. 14.8%, P < .001). The PJI rate was 2.4% for primary RSA and 2.6% for revision RSA. The incidence of glenoid and humeral component loosening was 2.3% and 1.4%, respectively. The Grammont design had an increased NI rate vs. all other designs combined (0.9% vs. 0.1%, P = .04). CONCLUSIONS: Focused systematic reviews of the recent literature with a large volume of RSAs demonstrate that with the use of non-Grammont modern prosthesis designs, complications including SN, PJI, glenoid component loosening, and NI are significantly reduced compared with previous studies. As the indications for RSA continue to expand, it is imperative to accurately track the rates and types of complications to justify its cost and increased indications.

Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors.

Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins, and biophysical studies identify interacting surfaces between irisin and αV/ß5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health.

Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and nociception.

N-acyl amino acids (NAAs) are a structurally diverse class of bioactive signaling lipids whose endogenous functions have largely remained uncharacterized. To clarify the physiologic roles of NAAs, we generated mice deficient in the circulating enzyme peptidase M20 domain-containing 1 (PM20D1). Global PM20D1-KO mice have dramatically reduced NAA hydrolase/synthase activities in tissues and blood with concomitant bidirectional dysregulation of endogenous NAAs. Compared with control animals, PM20D1-KO mice exhibit a variety of metabolic and pain phenotypes, including insulin resistance, altered body temperature in cold, and antinociceptive behaviors. Guided by these phenotypes, we identify N-oleoyl-glutamine (C18:1-Gln) as a key PM20D1-regulated NAA. In addition to its mitochondrial uncoupling bioactivity, C18:1-Gln also antagonizes certain members of the transient receptor potential (TRP) calcium channels including TRPV1. Direct administration of C18:1-Gln to mice is sufficient to recapitulate a subset of phenotypes observed in PM20D1-KO animals. These data demonstrate that PM20D1 is a dominant enzymatic regulator of NAA levels in vivo and elucidate physiologic functions for NAA signaling in metabolism and nociception.

Discovery of Hydrolysis-Resistant Isoindoline N-Acyl Amino Acid Analogues that Stimulate Mitochondrial Respiration.

N-Acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. We found that administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure, indicating that this pathway might be useful for treating obesity and associated disorders. We report the full account of the synthesis and mitochondrial uncoupling bioactivity of lipidated N-acyl amino acids and their unnatural analogues. Unsaturated fatty acid chains of medium length and neutral amino acid head groups are required for optimal uncoupling activity on mammalian cells. A class of unnatural N-acyl amino acid analogues, characterized by isoindoline-1-carboxylate head groups (37), were resistant to enzymatic degradation by PM20D1 and maintained uncoupling bioactivity in cells and in mice.