Inpatient or outpatient total elbow arthroplasty: a comparison of patient populations and 30-day surgical outcomes from the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: Total elbow arthroplasty (TEA) is uncommon, but growing in incidence. Traditionally an inpatient operation, a growing number are performed outpatient, consistent with general trends in orthopedic surgery. The aim of this study was to compare TEA outcomes between inpatient and outpatient surgical settings. Secondarily, we sought to identify patient characteristics that predict the operative setting. METHODS: Patient data were collected from the American College of Surgeons National Quality Improvement Program. Preoperative variables, including patient demographics and comorbidities, were recorded, and baseline differences were assessed via multivariate regression to predict operative setting. Multivariate regression was also used to compare postoperative complications within 30 days. RESULTS: A total of 468 patients, 303 inpatient and 165 outpatient procedures, were identified for inclusion. Hypoalbuminemia (odds ratio [OR], 2.5; P=0.029), history of chronic obstructive pulmonary disorder or pneumonia (OR, 2.4; P=0.029), and diabetes mellitus (OR, 2.5; P=0.001) were significantly associated with inpatient TEA, as were greater odds of any complication (OR, 4.1; P<0.001) or adverse discharge (OR, 4.5; P<0.001) and decreased odds of reoperation (OR, 0.4; P=0.037). CONCLUSIONS: Patients undergoing inpatient TEA are generally more comorbid, and inpatient surgery is associated with greater odds of complications and adverse discharge. However, we found higher rates of reoperation in outpatient TEA. Our findings suggest outpatient TEA is safe, although patients with a higher comorbidity burden may require inpatient surgery. Level of evidence: III.

De novo design of highly selective miniprotein inhibitors of integrins αvß6 and αvß8.

The RGD (Arg-Gly-Asp)-binding integrins αvß6 and αvß8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between homologous αvß6 and αvß8 and other RGD integrins, stabilize specific conformational states, and have high thermal stability could have considerable therapeutic utility. Existing small molecule and antibody inhibitors do not have all these properties, and hence new approaches are needed. Here we describe a generalized method for computationally designing RGD-containing miniproteins selective for a single RGD integrin heterodimer and conformational state. We design hyperstable, selective αvß6 and αvß8 inhibitors that bind with picomolar affinity. CryoEM structures of the designed inhibitor-integrin complexes are very close to the computational design models, and show that the inhibitors stabilize specific conformational states of the αvß6 and the αvß8 integrins. In a lung fibrosis mouse model, the αvß6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.

De novo design of highly selective miniprotein inhibitors of integrins αvß6 and αvß8.

The RGD (Arg-Gly-Asp)-binding integrins αvß6 and αvß8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins and other RGD integrins, stabilize specific conformational states, and have sufficient stability enabling tissue restricted administration could have considerable therapeutic utility. Existing small molecules and antibody inhibitors do not have all of these properties, and hence there is a need for new approaches. Here we describe a method for computationally designing hyperstable RGD-containing miniproteins that are highly selective for a single RGD integrin heterodimer and conformational state, and use this strategy to design inhibitors of αvß6 and αvß8 with high selectivity. The αvß6 and αvß8 inhibitors have picomolar affinities for their targets, and >1000-fold selectivity over other RGD integrins. CryoEM structures are within 0.6-0.7Å root-mean-square deviation (RMSD) to the computational design models; the designed αvß6 inhibitor and native ligand stabilize the open conformation in contrast to the therapeutic anti-αvß6 antibody BG00011 that stabilizes the bent-closed conformation and caused on-target toxicity in patients with lung fibrosis, and the αvß8 inhibitor maintains the constitutively fixed extended-closed αvß8 conformation. In a mouse model of bleomycin-induced lung fibrosis, the αvß6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics when delivered via oropharyngeal administration mimicking inhalation, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.

The Effect of Obesity on Distal Radius Fractures: An Analysis from the NSQIP Database.

The rate and severity of obesity has risen over the past 40 years, and class III (formerly morbid) obesity presents additional sequelae. The effect of obesity on the incidence and recovery of hand and wrist fractures remains unclear. We sought to quantify the relationship between class III obesity and postoperative distal radius fracture (DRF) complications. Methods: We performed a retrospective analysis of the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database for surgical DRF patients more than 50 years old from 2015 to 2020. We then stratified patients into class III obese (BMI > 40) and compared the rates of postoperative complications to a control group with BMI less than 40. Results: We included 10,022 patients (570 class III obese vs. 9,452 not class III obese). Patients with class III obesity had significantly increased odds of experiencing any complication (OR 1.906, p<0.001), adverse discharge (OR 2.618, p<0.001), delayed hospital stay of longer than three days (OR 1.91, p<0.001), and longer than seven days (OR 2.943, p<0.001) than controls. They also had increased odds of unplanned reoperation (OR 2.138, p = 0.026) and readmission (OR 2.814, p < 0.001) than non-class III obese patients. Class III obese patients had a significantly longer average operation time (79.5 min vs. 72.2 min, p < 0.001). They also spent more time in the hospital postoperatively (0.86 days vs. 0.57 days, p = 0.001). Conclusion: Class III obese patients undergoing DRF repair are more likely to experience postoperative complications than non-class III obese patients.