Preoperative Hip Injection Response Does Not Reliably Predict 2-Year Postoperative Outcomes Following Hip Arthroscopy for Femoroacetabular Impingement.

PURPOSE: To determine whether response to preoperative local anesthetic or corticosteroid intra-articular injections can predict 2-year postoperative outcomes in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). METHODS: This was a retrospective analysis of patients undergoing hip arthroscopy for FAIS at a single institution from 2014-2020. Patients who underwent preoperative intra-articular hip injection were classified based on injection type (local anesthetic, corticosteroid) and whether they experienced pain relief following injection (responders, non-responders). Responders were matched 2:1 by age, BMI, and sex with non-responders. Patient reported outcomes (PROs) including Hip Disability and Osteoarthritis Outcome Score (HOOS), 12-item Short-Form Survey mental (SF-12-MCS) and physical component summary (SF-12-PCS) and visual analogue scale (VAS) pain were collected preoperatively and 2-years postoperatively. Mean score change and Minimal Clinically Important Difference (MCID) achievement were calculated and compared between groups. RESULTS: The matched cohort included 126 total patients (42 non-responders, 84 responders; 74.6% female; mean ± SD age: 30.9 ± 9.9 years; BMI: 24.7 ± 3.7 kg/m2) with no differences in demographic or radiographic hip variables. Both groups demonstrated significant 2-year postoperative score improvements across all PROs, except SF-12-MCS, which remained unchanged. There was no difference in mean score change or MCID achievement across all PROs between corticosteroid injection responder and non-responder groups. In the local anesthetic group, MCID achievement was similar across all PROs, except VAS pain which showed greater percentage of MCID achievement among local anesthetic non-responders relative responders (Responders: 55.0%, Non-responders: 89.5%; p = 0.03). Significant ceiling effects were most readily apparent among the injection responders group with greater percentages of patients achieving maximal 2-year postoperative survey scores (36.9% HOOS-ADL, 19.0% HOOS-Pain, 15.5% HOOS-QoL, 32.1% HOOS-Sport). CONCLUSIONS: Response to preoperative injection with either corticosteroid or local anesthetic did not predict 2-year outcomes after hip arthroscopy in patients with FAIS. LEVEL OF EVIDENCE: Level III, retrospective matched cohort study.

Early Opioid Use and Postoperative Delirium Following Open Abdominal Aortic Aneurysm Repair.

OBJECTIVES: Postoperative delirium is a common complication following open abdominal aortic aneurysm repair (OAR). Opioids have been found to contribute to delirium, especially at higher doses. This study assessed the impact of early postoperative opioid analgesia on postoperative delirium incidence and time to onset. We hypothesized that higher early postoperative opioid utilization would be associated with increased postoperative delirium incidence. METHODS: This was a retrospective analysis of OAR cases at a single quaternary care center from years 2012-2020. The primary exposure was oral morphine equivalents use (OME), calculated for postoperative days 1-7. A cut point analysis using a receiver operator curve for postoperative delirium determined the threshold for high OME (OME>37mg). The primary outcome was postoperative delirium incidence identified via chart review. Multivariable logistic regression was performed for postoperative delirium and adjusted for covariates meeting p<0.1 on bivariate analysis. RESULTS: Among 194 OAR cases, 67 (35%) developed postoperative delirium with median time to onset of 3 days (IQR=2-6). Patients with postoperative delirium were older (74 years vs 69 years), more frequently presented with symptomatic AAA (47% vs 27%) and had a higher proportion of comorbidities (all p<0.05). Cases with high OME utilization on postoperative day 1 (55%) were younger (69 vs 73 years), less frequently had an epidural (46% vs 77%), and more frequently developed delirium (42% vs 25%, all p<0.05). Epidural use was associated with a significant decrease in OME utilization on postoperative day 1 (33 vs 83, p<0.01). Postoperative delirium onset was later in those with high OME use (4 vs 2 days, p=0.04). On multivariable analysis, high OME remained associated with postoperative delirium (Table II). CONCLUSION: High opioid utilization on postoperative day 1 is associated with increased postoperative delirium and epidural along with acetaminophen use reduced opioid utilization. Future study should examine the impact of opioid reduction strategies on outcomes after major vascular surgery.

MiR-30 promotes fatty acid beta-oxidation and endothelial cell dysfunction and is a circulating biomarker of coronary microvascular dysfunction in pre-clinical models of diabetes.

BACKGROUND: Type 2 diabetes (T2D) is associated with coronary microvascular dysfunction, which is thought to contribute to compromised diastolic function, ultimately culminating in heart failure with preserved ejection fraction (HFpEF). The molecular mechanisms remain incompletely understood, and no early diagnostics are available. We sought to gain insight into biomarkers and potential mechanisms of microvascular dysfunction in obese mouse (db/db) and lean rat (Goto-Kakizaki) pre-clinical models of T2D-associated diastolic dysfunction. METHODS: The microRNA (miRNA) content of circulating extracellular vesicles (EVs) was assessed in T2D models to identify biomarkers of coronary microvascular dysfunction/rarefaction. The potential source of circulating EV-encapsulated miRNAs was determined, and the mechanisms of induction and the function of candidate miRNAs were assessed in endothelial cells (ECs). RESULTS: We found an increase in miR-30d-5p and miR-30e-5p in circulating EVs that coincided with indices of coronary microvascular EC dysfunction (i.e., markers of oxidative stress, DNA damage/senescence) and rarefaction, and preceded echocardiographic evidence of diastolic dysfunction. These miRNAs may serve as biomarkers of coronary microvascular dysfunction as they are upregulated in ECs of the left ventricle of the heart, but not other organs, in db/db mice. Furthermore, the miR-30 family is secreted in EVs from senescent ECs in culture, and ECs with senescent-like characteristics are present in the db/db heart. Assessment of miR-30 target pathways revealed a network of genes involved in fatty acid biosynthesis and metabolism. Over-expression of miR-30e in cultured ECs increased fatty acid ß-oxidation and the production of reactive oxygen species and lipid peroxidation, while inhibiting the miR-30 family decreased fatty acid ß-oxidation. Additionally, miR-30e over-expression synergized with fatty acid exposure to down-regulate the expression of eNOS, a key regulator of microvascular and cardiomyocyte function. Finally, knock-down of the miR-30 family in db/db mice decreased markers of oxidative stress and DNA damage/senescence in the microvascular endothelium. CONCLUSIONS: MiR-30d/e represent early biomarkers and potential therapeutic targets that are indicative of the development of diastolic dysfunction and may reflect altered EC fatty acid metabolism and microvascular dysfunction in the diabetic heart.