Cardioprotective O-GlcNAc signaling is elevated in murine female hearts via enhanced O-GlcNAc transferase activity.

The post-translational modification of intracellular proteins by O-linked ß-GlcNAc (O-GlcNAc) has emerged as a critical regulator of cardiac function. Enhanced O-GlcNAcylation activates cytoprotective pathways in cardiac models of ischemia-reperfusion (I/R) injury; however, the mechanisms underpinning O-GlcNAc cycling in response to I/R injury have not been comprehensively assessed. The cycling of O-GlcNAc is regulated by the collective efforts of two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), which catalyze the addition and hydrolysis of O-GlcNAc, respectively. It has previously been shown that baseline heart physiology and pathophysiology are impacted by sex. Here, we hypothesized that sex differences in molecular signaling may target protein O-GlcNAcylation both basally and in ischemic hearts. To address this question, we subjected male and female WT murine hearts to ex vivo ischemia or I/R injury. We assessed hearts for protein O-GlcNAcylation, abundance of OGT, OGA, and glutamine:fructose-6-phosphate aminotransferase (GFAT2), activity of OGT and OGA, and UDP-GlcNAc levels. Our data demonstrate elevated O-GlcNAcylation in female hearts both basally and during ischemia. We show that OGT activity was enhanced in female hearts in all treatments, suggesting a mechanism for these observations. Furthermore, we found that ischemia led to reduced O-GlcNAcylation and OGT-specific activity. Our findings provide a foundation for understanding molecular mechanisms that regulate O-GlcNAcylation in the heart and highlight the importance of sex as a significant factor when assessing key regulatory events that control O-GlcNAc cycling. These data suggest the intriguing possibility that elevated O-GlcNAcylation in females contributes to reduced ischemic susceptibility.

Differential Detection of O-GlcNAcylated proteins in the heart using antibodies.

Thousands of mammalian intracellular proteins are dynamically modified by O-linked ß-N-acetylglucosamine (O-GlcNAc). Global changes in O-GlcNAcylation have been associated with the development of cardiomyopathy, heart failure, hypertension, and neurodegenerative disease. Levels of O-GlcNAc in cells and tissues can be detected using numerous approaches; however, immunoblotting using GlcNAc-specific antibodies and lectins is commonplace. The goal of this study was to optimize the detection of O-GlcNAc in heart lysates by immunoblotting. Using a combination of tissue fractionation, immunoblotting, and galactosyltransferase labeling, as well as hearts from wild-type and O-GlcNAc transferase transgenic mice, we demonstrate that contractile proteins in the heart are differentially detected by two commercially available antibodies (CTD110.6 and RL2). As CTD110.6 displays poor reactivity toward contractile proteins, and as these proteins represent a major fraction of the heart proteome, a better assessment of cardiac O-GlcNAcylation is obtained in total tissue lysates with RL2. The data presented highlight tissue lysis approaches that should aid the assessment of the cardiac O-GlcNAcylation by immunoblotting.

Diffusivity of Human Cartilage Endplates in Healthy and Degenerated Intervertebral Disks.

The cartilage endplates (CEPs) on the superior and inferior surfaces of the intervertebral disk (IVD), are the primary nutrient transport pathways between the disk and the vertebral body. Passive diffusion is responsible for transporting small nutrient and metabolite molecules through the avascular CEPs. The baseline solute diffusivities in healthy CEPs have been previously studied, however alterations in CEP diffusion associated with IVD degeneration remain unclear. This study aimed to quantitatively compare the solute diffusion in healthy and degenerated human CEPs using a fluorescence recovery after photobleaching (FRAP) approach. Seven healthy CEPs and 22 degenerated CEPs were collected from five fresh-frozen human cadaveric spines and 17 patients undergoing spine fusion surgery, respectively. The sodium fluorescein diffusivities in CEP radial and vertical directions were measured using the FRAP method. The CEP calcification level was evaluated by measuring the average X-ray attenuation. No difference was found in solute diffusivities between radial and axial directions in healthy and degenerated CEPs. Compared to healthy CEPs, the average solute diffusivity was 44% lower in degenerated CEPs (Healthy: 29.07 µm2/s (CI: 23.96-33.62 µm2/s); degenerated: 16.32 µm2/s (CI: 13.84-18.84 µm2/s), p < 0.001). The average solute diffusivity had an inverse relationship with the degree of CEP calcification as determined by the normalized X-ray attenuation values (ß = -22.19, R2 = 0.633; p < 0.001). This study suggests that solute diffusion through the disk and vertebral body interface is significantly hindered by CEP calcification, providing clues to help further understand the mechanism of IVD degeneration.

Performance of a Severity Score on Admission Chest Radiography in Predicting Clinical Outcomes in Hospitalized Patients With Coronavirus Disease (COVID-19).

BACKGROUND. Chest radiographs (CXRs) are typically obtained early in patients admitted with coronavirus disease (COVID-19) and may help guide prognosis and initial management decisions. OBJECTIVE. The purpose of this study was to assess the performance of an admission CXR severity scoring system in predicting hospital outcomes in patients admitted with COVID-19. METHODS. This retrospective study included 240 patients (142 men, 98 women; median age, 65 [range, 50-80] years) admitted to the hospital from March 16 to April 13, 2020, with COVID-19 confirmed by real-time reverse-transcriptase polymerase chain reaction who underwent chest radiography within 24 hours of admission. Three attending chest radiologists and three radiology residents independently scored patients' admission CXRs using a 0- to 24-point composite scale (sum of scores that range from 0 to 3 for extent and severity of disease in upper and lower zones of left and right lungs). Interrater reliability of the score was assessed using the Kendall W coefficient. The mean score was obtained from the six readers' scores for further analyses. Demographic variables, clinical characteristics, and admission laboratory values were collected from electronic medical records. ROC analysis was performed to assess the association between CXR severity and mortality. Additional univariable and multivariable logistic regression models incorporating patient characteristics and laboratory values were tested for associations between CXR severity and clinical outcomes. RESULTS. Interrater reliability of CXR scores ranged from 0.687 to 0.737 for attending radiologists, from 0.653 to 0.762 for residents, and from 0.575 to 0.666 for all readers. A composite CXR score of 10 or higher on admission achieved 53.0% (35/66) sensitivity and 75.3% (131/174) specificity for predicting hospital mortality. Hospital mortality occurred in 44.9% (35/78) of patients with a high-risk admission CXR score (≥ 10) versus 19.1% (31/162) of patients with a low-risk CXR score (< 10) (p < .001). Admission composite CXR score was an independent predictor of death (odds ratio [OR], 1.17; 95% CI, 1.10-1.24; p < .001). composite CXR score was a univariable predictor of intubation (OR, 1.23; 95% CI, 1.12-1.34; p < .001) and continuous renal replacement therapy (CRRT) (OR, 1.15; 95% CI, 1.04-1.27; p = .007) but was not associated with these in multivariable models (p > .05). CONCLUSION. For patients admitted with COVID-19, an admission CXR severity score may help predict hospital mortality, intubation, and CRRT. CLINICAL IMPACT. CXR may assist risk assessment and clinical decision-making early in the course of COVID-19.

Elevated BMI increases concurrent pathology and operative time in adolescent ACL reconstruction.

PURPOSE: The purpose of this study was to (1) report on the incidence of concurrent surgical pathology at the time of adolescent ACL reconstruction, (2) evaluate patient risk factors for concurrent pathology, and (3) measure the effect of BMI on operating room (OR) time. METHODS: A retrospective analysis of the NSQIP database for the years 2005-2017 was conducted. Nine-hundred and seventeen patients 18 years of age and younger who underwent ACL reconstruction (ACLR) were identified using CPT code 29888 and patients undergoing surgery for multi-ligamentous knee injuries were excluded. The mean patient age was 17.6 years (range 14-18, standard deviation 0.52) and consisted of 546 males (59.5%) and 371 females (40.5%). Logistic regression was used to assess the relationship between BMI and additional CPT codes for internal derangement at the time of surgery. Internal derangement was defined as any procedure for the treatment of a meniscal tear, chondral lesion, or loose body removal. Linear regression analysis was then performed to evaluate the effect of BMI on operative time. RESULTS: 43.7% of patients undergoing ACLR required an associated procedure for internal derangement. Additionally, the risk of requiring additional procedures for internal derangement increased by 3.1% per BMI point. BMI was also predictive of operative time, independent of the number of additional procedures. Specifically, the operative time increased by nearly one minute for every point increase in BMI (58.0 s). CONCLUSIONS: Adolescent patients with an elevated BMI were much more likely to require additional surgical procedures for internal derangement at the time of ACL reconstruction. Additionally, BMI was a significant predictor for longer operative times. LEVEL OF EVIDENCE: Level III.

The Fate of Morbidly Obese Patients With Joint Pain: A Retrospective Study of Patient Outcomes.

BACKGROUND: The number of obese patients seeking a total joint arthroplasty (TJA) continues to increase. Weight loss is often recommended to treat joint pain and reduce risks associated with TJA. We sought to determine the effectiveness of an orthopedic surgeon's recommendation to lose weight. METHODS: We identified morbidly obese (body mass index (BMI) 40-49.9 kg/m2) and super obese (BMI ≥50 kg/m2) patients with hip or knee osteoarthritis. Patients with less than 3-month follow-up were excluded. Patient characteristics (age, gender, BMI, comorbidities), disease characteristics (joint affected, radiographic osteoarthritis grading), and treatments were recorded. Clinically meaningful weight loss was defined as weight loss greater than 5%. RESULTS: Two hundred thirty morbid and 50 super obese patients were identified. Super obese patients were more likely to be referred to weight management (52.0% vs 21.7%, P < .001) and were less likely to receive TJA (20.0% vs 41.7%, P = .004). Each 1 kg/m2 increase in BMI decreased the odds of TJA by 10.9% (odds ratio = 0.891, 95% confidence interval: 0.833-0.953, P = .001). Forty (23.0%) of the nonoperatively treated patients achieved clinically meaningful weight loss, and 19 (17.9%) patients who underwent TJA lost weight before surgery. After surgery, the number of patients who achieved a clinically meaningful weight loss grew to 32 (30.2%). CONCLUSION: In morbid and super obese patients, increasing BMI reduces the likelihood that a patient will receive TJA, and when counseled by their orthopedic surgeon, few patients participate in weight-loss programs or are otherwise able to lose weight. Weight loss is an inconsistently modifiable risk factor for joint replacement surgery.

The 5-Factor Modified Frailty Index Predicts Complications, Hospital Admission, and Mortality Following Arthroscopic Rotator Cuff Repair.

INTRODUCTION: The purpose of this study is to evaluate the utility of the modified frailty index-5 (mFI-5) as a predictor for postoperative complications in patients undergoing arthroscopic rotator cuff repair (RCR). METHODS: The National Surgical Quality Improvement Program database was queried for patients undergoing arthroscopic RCR between 2006 and 2016. The mFI-5, a 5-factor score comprising comorbid diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and functional status limiting independence, was calculated for each patient. Multivariate logistic regression models were used to evaluate the mFI-5 score as a predictor for complications including medical complications, surgical-site infections, hospital admission, discharge to a facility, and mortality. RESULTS: In total, 24,477 patients met criteria for inclusion. The mFI-5 was a strong predictor for medical complications (P < .001), hospital admission (P < .001), length of stay (P = .007), and discharge to a facility (P = .001) but not surgical-site infections (P = .153). For each point increase in mFI-5 score, the risk for a medical complication increased by 66%, readmission by 52%, and adverse discharge by 45%. However, of all the measured complications, the mFI-5 was the strongest predictor for mortality, with the risk more than doubling for each increase in mFI-5 point (odds ratio 2.66, P = .025). CONCLUSIONS: The mFI-5 is a sensitive tool for predicting life-threatening medical complications, hospital admission, increased length of stay, adverse discharge, and mortality following arthroscopic RCR. The 5 comorbidities comprising the mFI-5 are easily obtained through the patient history, making it a practical clinical tool for identifying high-risk patients, informing preoperative counseling, and improving value-based health care. LEVEL OF EVIDENCE: Level III, prognostic.

Smoking is associated with increased surgical complications following total shoulder arthroplasty: an analysis of 14,465 patients.

HYPOTHESIS: The purpose of this study was to evaluate the association between smoking and postoperative complications following total shoulder arthroplasty. We hypothesized that active smokers would have significantly greater postoperative medical and surgical complications. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent total shoulder arthroplasties from 2005 through 2016. Patients were stratified based on tobacco use within the past year. Logistic regression was used to assess the relationship between smoking status and postoperative medical and surgical complications. Multivariate logistic regression was used to adjust for demographic and comorbid factors. RESULTS: We identified 14,465 patients, of whom 10.5% were active smokers. Smokers were more likely to be younger, to be female patients, and to have a lower body mass index compared with nonsmokers (P < .001). Univariate analysis demonstrated that smoking was not associated with postoperative medical complications (P > .05) but was associated with an increased risk of overall surgical complications (odds ratio [OR], 3.259; 95% confidence interval [CI], 1.861-5.709; P < .001). Multivariate modeling showed that smoking increased the risk of wound complications (adjusted OR, 7.564; 95% CI, 2.128-26.889; P = .002) and surgical-site infections (adjusted OR, 1.927; 95% CI, 1.023-3.630; P = .042). DISCUSSION AND CONCLUSION: This study demonstrates that smoking is associated with an increased risk of surgical complications following total shoulder arthroplasty. On the basis of our available data, medical complications are not significantly increased. This information can help risk stratify patients prior to their procedures.

Insulin Dependence Is Associated With Increased Medical Complications and Mortality After Shoulder Arthroscopy.

PURPOSE: To compare complications after shoulder arthroscopy in patients with insulin-dependent diabetes mellitus (IDDM), patients with non-insulin-dependent diabetes mellitus (NIDDM), and nondiabetic patients. METHODS: A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database for the years 2005 to 2016 was conducted. Logistic regression analyses were used to assess the relation between diabetic status (nondiabetic patients, n = 50,626; NIDDM patients, n = 5,332; and IDDM patients, n = 2,484) and outcomes. Multivariate models were established to adjust for age, sex, body mass index, hypertension, congestive heart failure, chronic obstructive pulmonary disease, smoking status, American Society of Anesthesiologists classification, and functional status. RESULTS: Patients with IDDM were at a higher risk of medical complications, with an adjusted odds ratio (AOR) of 1.524 (95% confidence interval [CI], 1.082-2.147), including pulmonary complications (AOR, 2.078; 95% CI, 1.089-3.964) and urinary tract infections (AOR, 2.129; 95% CI, 1.027-4.415). Patients with IDDM also had a higher risk of 30-day hospital admission (AOR, 1.581; 95% CI, 1.153-2.169) and 30-day mortality (AOR, 3.821; 95% CI, 1.243-11.750). Conversely, patients with NIDDM had comparable risks of medical and surgical complications, unplanned hospital admission, and death to nondiabetic patients. CONCLUSIONS: Medical complications, 30-day hospital admission, and death after shoulder arthroscopy were more likely in patients with IDDM. These risks diminished among patients with NIDDM, with their risks being comparable with those of nondiabetic patients. LEVEL OF EVIDENCE: Level III, retrospective comparison study.

Higher BMI predicts additional surgery at the time of ACL reconstruction.

PURPOSE: Despite public recognition, obesity is a growing epidemic affecting an estimated 34% of adults and 20% of children in the U.S. POPULATION: As such, the number of ACL reconstructions performed in this population is likely to increase. The goal of this study is to evaluate the risk that increasing BMI poses for additional surgery at the time of ACL reconstruction. METHODS: A retrospective analysis of the American College of Surgeons' National Surgical Quality Improvement Program's (ACS-NSQIP) database for the years 2005-2015 was conducted. Logistic regressions were used to assess the relationship between BMI and additional CPT codes for internal derangement at the time of ACL reconstruction. Internal derangement was defined as any CPT code for treatment of a meniscus tear, chondral lesion, or loose body removal. Surgeries for multi-ligamentous knee injuries were excluded. RESULTS: A total of 11,403 patients undergoing ACL reconstruction were identified. 41.9% of patients had an associated CPT code for internal derangement. As BMI increased, there was a corresponding increase in the odds of additional surgery. Specifically, for every 1.0 increase in BMI, the risk of additional surgery increased by 1.6% (p < 0.001). Compared to patients with a BMI of 18.5-24.9, those with a BMI 25-29.9 had an odds ratio (OR) of 1.112, BMI 30-34.9 had an OR of 1.137, BMI 35-39.9 had an OR of 1.249, and those ≥ 40 had an OR of 1.442 for additional surgery (p < 0.001). CONCLUSIONS: This nationally-representative, population-based study demonstrates that patients with elevated BMI are much more likely to require additional surgery in the setting of primary ACL reconstruction. This risk correlates with increasing BMI. Surgeons should keep these risks in mind when evaluating and counseling patients for surgery in the setting of ACL reconstruction. LEVEL OF EVIDENCE: Case-control study, Level III.

Smoking is associated with increased complications and readmission following extensor mechanism repair.

PURPOSE: Extensor mechanism injuries are disabling injuries that require prompt evaluation and treatment and complications are often devastating. While smoking has been shown to increase complications following total joint arthroplasty, this relationship has not yet been established in those undergoing extensor mechanism repair. The purpose of this study was to evaluate the risk of smoking on postoperative complications following extensor mechanism repair. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used to identify patients who underwent an extensor mechanism repair from 2005 to 2016. Patients were stratified by tobacco use, as either "current" or "nonsmokers." A multivariate logistic regression was used to control for demographic and comorbid factors while assessing perioperative complications. RESULTS: 5208 patients were identified, and of these, 843 (16.2%) were current smokers. Smokers were younger, male, and with lower BMIs compared to nonsmokers (p = 0.001, p = 0.003, p = 0.002, respectively). They had a higher rate of surgical complications (OR 1.61, CI 1.02-2.52), including deep surgical site infections (OR 3.27, CI 1.03-10.43) and unplanned return to the operating room (OR 2.001, 1.24-3.23). Smokers were more likely to be readmitted within 30 days of surgery (OR 1.78, OR 1.09-2.90). CONCLUSION: Tobacco use is associated with a 1-2% increase in surgical, but not medical, complications following repair of extensor mechanism injuries. Smokers are at higher risk for deep infections, unplanned return to the OR, and hospital readmission. Identifying these patients preoperatively will allow surgeons to accurately counsel patients on perioperative risks. Counseling in preoperative smoking cessation is valuable for optimizing patient outcomes following extensor mechanism repair. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.

Modified frailty index predicts medical complications, length of stay, readmission, and mortality following total shoulder arthroplasty.

HYPOTHESIS: The purpose of this study was to evaluate the 5-factor modified frailty index (mFI-5) as a predictor of postoperative complications in patients undergoing total shoulder arthroplasty (TSA). METHODS: We conducted a retrospective analysis of the National Surgical Quality Improvement Program database for patients undergoing TSA between the years 2005 and 2017. The mFI-5 score, which includes the presence of comorbid diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and functional status, was calculated for each patient. Multivariate logistic regression models were used to assess the relationship between the mFI-5 and postoperative complications. RESULTS: A total of 18,957 patients undergoing TSA were identified. The mFI-5 was a strong predictor of serious medical complications (cardiac arrest, myocardial infarction, septic shock, pulmonary embolism, postoperative dialysis, reintubation, and prolonged ventilator requirement), discharge to a facility, and readmission (odds ratio ≥ 1.309, P ≤ .001). Length of stay also increased as the mFI-5 score increased (P < .001). However, among all the measured complications, the mFI-5 was the strongest predictor of mortality, with the risk more than doubling for each point increase in the mFI-5 score (odds ratio, 2.113; 95% confidence interval, 1.447-3.086; P < .001). CONCLUSION: The mFI-5 predicts serious medical complications, increased length of stay, discharge to a facility, hospital readmission, and mortality in patients undergoing TSA. All of the variables within the mFI-5 are easily obtained through the patient history, allowing for a practical clinical tool that hospitals and surgeons can use to identify high-risk surgical candidates, inform preoperative counseling, and guide perioperative care to optimize patient outcomes.

Frailty Predicts Medical Complications, Length of Stay, Readmission, and Mortality in Revision Hip and Knee Arthroplasty.

BACKGROUND: The purpose of this study is to evaluate the 5-factor modified frailty index (mFI-5) as a predictor of postoperative complications, readmission, and mortality in patients undergoing revision hip and knee arthroplasty. METHODS: A retrospective analysis of the American College of Surgeon's National Surgical Quality Improvement Program's database for patients undergoing revision total hip arthroplasty (rTHA) and revision total knee arthroplasty (rTKA) between the years 2005 and 2016 was conducted. The 5-factor score, which includes presence of comorbid diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and functional status, was calculated for each patient. Multivariate logistic regression models were used to assess the relationship between the mFI-5 and postoperative complications while controlling for demographic variables. RESULTS: In total, 13,948 patients undergoing rTHA and 16,304 patients undergoing rTKA were identified. The mFI-5 was a strong predictor of serious medical complications (cardiac arrest, myocardial infarction, septic shock, pulmonary embolism, postoperative dialysis, reintubation, and prolonged ventilator requirement), discharge to a facility, total length of stay, readmission, and mortality (P ≤ .007). CONCLUSION: The mFI-5 predicts serious medical complications, increased length of stay, discharge to a facility, hospital readmission, and mortality in patients undergoing rTHA and rTKA. All the variables within the mFI-5 are easily obtained through the patient history, allowing for a practical clinical tool that hospitals and physicians can use to identify at-risk patients, educate and engage patients and their families in a shared decision-making conversation, and guide perioperative care in order to optimize patient outcomes. LEVEL OF EVIDENCE: III.

New 5-Factor Modified Frailty Index Predicts Morbidity and Mortality in Primary Hip and Knee Arthroplasty.

BACKGROUND: While the 11-factor modified frailty index (mFI) has been shown to predict adverse outcomes in patients undergoing total joint arthroplasty, the 5-factor index has not been evaluated in this patient population. The goal of this study was to evaluate the utility of the mFI-5 as a predictor of morbidity and mortality in patients undergoing primary total hip and knee arthroplasty. METHODS: A retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program's database for patients undergoing total hip arthroplasty and total knee arthroplasty between the years 2005 and 2016 was conducted. The 5-factor score, which includes the presence of comorbid diabetes, hypertension, congestive heart failure, chronic obstructive pulmonary disease, and functional status, was calculated for each patient. Multivariate logistic regression models were used to assess the relationship between the mFI-5 and postoperative complications while controlling for demographic variables. RESULTS: One hundred forty thousand one hundred fifty-eight patients undergoing total hip arthroplasty and 226,398 patients undergoing total knee arthroplasty were identified. After adjusting for demographic variables and comorbid conditions, logistic regression analyses revealed that the mFI-5 was a strong predictor for total complications, Clavien-Dindo grade IV complications (cardiac arrest, myocardial infarction, septic shock, pulmonary embolism, postoperative dialysis, reintubation, and prolonged ventilator requirement), surgical site infections, readmission, and 30-day mortality (P < .001). CONCLUSIONS: The mFI-5 is an independent predictor of postoperative complications including life-threatening medical complications, surgical site infections, hospital readmission, and 30-day mortality after primary hip and knee arthroplasty. This clinical tool can be used to identify high-risk surgical patients and guide preoperative counseling to optimize outcomes. LEVEL OF EVIDENCE: III.

External Beam Irradiation Preferentially Inhibits the Endochondral Pathway of Fracture Healing: A Rat Model.

BACKGROUND: External beam irradiation is an accepted treatment for skeletal malignancies. Radiation acts on both cancerous and normal cells and, depending on the balance of these effects, may promote or impair bone healing after pathologic fracture. Previous studies suggest an adverse effect of radiation on endochondral ossification, but the existence of differential effects of radiation on the two distinct bone healing pathways is unknown. QUESTIONS/PURPOSES: The purpose of this study was to investigate the differential effects of external beam irradiation on endochondral compared with intramembranous ossification with intramedullary nail and plate fixation of fractures inducing the two respective osseous healing pathways through assessment of (1) bone biology by histomorphometric analysis of cartilage area and micro-CT volumetric assessment of the calcified callus; and (2) mechanical properties of the healing fracture by four-point bending failure analysis of bending stiffness and strength. METHODS: Thirty-six male Sprague-Dawley rats underwent bilateral iatrogenic femur fracture: one side was repaired with an intramedullary nail and the other with compression plating. Three days postoperatively, half (n = 18) received 8-Gray external beam irradiation to each fracture. Rodents were euthanized at 1, 2, and 4 weeks postoperatively (n = 3/group) for quantitative histomorphometry of cartilage area and micro-CT assessment of callus volume. The remaining rodents were euthanized at 3 months (n = 9/group) and subjected to four-point bending tests to assess stiffness and maximum strength. RESULTS: Nailed femurs that were irradiated exhibited a reduction in cartilage area at both 2 weeks (1.08 ± 1.13 mm versus 37.32 ± 19.88 mm; 95% confidence interval [CI] of the difference, 4.32-68.16 mm; p = 0.034) and 4 weeks (4.60 ± 3.97 mm versus 39.10 ± 16.28 mm; 95% CI of the difference, 7.64-61.36 mm; p = 0.023) compared with nonirradiated fractures. There was also a decrease in the volume ratio of calcified callus at 4 weeks (0.35 ± 0.08 versus 0.51 ± 0.05; 95% CI of the difference, 0.01-0.31; p = 0.042) compared with nonirradiated fractures. By contrast, there was no difference in cartilage area or calcified callus between irradiated and nonirradiated plated femurs. The stiffness (128.84 ± 76.60 N/mm versus 26.99 ± 26.07 N/mm; 95% CI of the difference, 44.67-159.03 N/mm; p = 0.012) and maximum strength (41.44 ± 22.06 N versus 23.75 ± 11.00 N; 95% CI of the difference, 0.27-35.11 N; p = 0.047) of irradiated plated femurs was greater than the irradiated nailed femurs. However, for nonirradiated femurs, the maximum strength of nailed fractures (36.05 ± 17.34 N versus 15.63 ± 5.19 N; 95% CI of the difference, 3.96-36.88 N; p = 0.022) was greater than plated fractures, and there was no difference in stiffness between the nailed and plated fractures. CONCLUSIONS: In this model, external beam irradiation was found to preferentially inhibit endochondral over intramembranous ossification with the greatest impairment in healing of radiated fractures repaired with intramedullary nails compared with those fixed with plates. Future work with larger sample sizes might focus on further elucidating the observed differences in mechanical properties. CLINICAL RELEVANCE: This work suggests that there may be a rationale for compression plating rather than intramedullary nailing of long bone fractures in select circumstances where bony union is desirable, adjunctive radiation treatment is required, and bone stock is sufficient for plate and screw fixation.

Costs and Risk Factors for Hospital Readmission After Periprosthetic Knee Fractures in the United States.

BACKGROUND: Periprosthetic fractures (PPFX) around total knee arthroplasty (TKA) are devastating complications with significant morbidity. With growing healthcare costs, hospital readmissions have become a marker for quality healthcare delivery. However, little is known about the risk factors or costs associated with readmission after treatment of PPFX. We sought to identify the patient demographics, prevalence of treatment types (open reduction internal fixation [ORIF] vs revision TKA), 30 and 90-day readmission rates, costs of initial treatment and readmission, and risk factors for readmission. METHODS: We used the 2013 Nationwide Readmissions Database to select patients who underwent TKA, revision TKA, and treatment of PPFX with either ORIF or revision TKA. The 90-day readmission rate was determined through a survival analysis, and risk factors were identified using a cox proportional hazards model that adjusted for patient and hospital characteristics. RESULTS: We identified 1526 patients with PPFX treated with ORIF and 1458 treated with revision TKA. Ninety-day readmissions were 20.5% and 21.8%, respectively. Patients with ORIF were more often female and had multiple medical comorbidities. Patient factors associated with readmission included advanced age, male gender, comorbidities, discharge to a skilled nursing facility or home with health aide, and Medicare or Medicaid insurance. Treatment at a teaching hospital was the only hospital-associated risk factor identified. ORIF cost USD 25,539 and revision THA cost USD 37,680, with associated readmissions costing 15,269 and 16,806, respectively. CONCLUSION: PPFX results in greater costs compared to primary and revision TKA. This study highlights risk factors for readmission after PPFX treatment.

Characterization of the specificity of O-GlcNAc reactive antibodies under conditions of starvation and stress.

The dynamic modification of nuclear, cytoplasmic, and mitochondrial proteins by O-linked ß-N-acetyl-D-glucosamine (O-GlcNAc) has been shown to regulate over 3000 proteins in a manner analogous to protein phosphorylation. O-GlcNAcylation regulates the cellular stress response and the cell cycle, and is implicated in the etiology of neurodegeneration, type II diabetes, and cancer. The antibody CTD110.6 is often used to detect changes in the O-GlcNAc modification. Recently, it has been demonstrated that CTD110.6 recognizes N-linked N,N'-diacetylchitobiose, which is thought to accumulate in cells experiencing severe glucose deprivation. In this study, we have addressed two questions: (1) Which other antibodies used to detect O-GlcNAc cross-react with N-linked N,N'-diacetylchitobiose? (2) Does N-linked N,N'-diacetylchitobiose accumulate in response to other cellular stressors? To delineate between O-GlcNAc and N-linked N,N'-diacetylchitobiose, we developed a workflow that has been used to confirm the specificity of a variety of O-GlcNAc-specific antibodies. Using this workflow we demonstrated that heat shock, osmotic stress, endoplasmic reticulum stress, oxidative stress, DNA damage, proteasomal inhibition, and ATP depletion induce O-GlcNAcylation but not N-linked N,N'-diacetylchitobiose. Moreover, we demonstrated that while glucose deprivation results in an induction in both O-GlcNAc and N-linked N,N'-diacetylchitobiose, the induction of N-linked N,N'-diacetylchitobiose is exacerbated by the removal of fetal bovine serum.

Evaluation of Achilles Tendon Stiffness as Measured by Shear Wave Elastography in Female College Athletes Compared With Nonathletes.

BACKGROUND: We sought to utilize a noninvasive technology to assess the effects of activity on Achilles tendon stiffness and define baseline Achilles tendon stiffness in female college athletes compared with nonathletes using tendon shear wave velocity as a marker for tendon stiffness. HYPOTHESIS: Training status and exercise may affect Achilles tendon stiffness. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 32 college-age female athletes were prospectively enrolled (n = 17 varsity athletes and n = 15 nonathletes). Demographic characteristics, activity level, and previous injuries were recorded. Sonographic shear wave elastography (SWE) was used to assess Achilles tendon shear wave velocity bilaterally for all subjects, both at baseline and after 2 minutes of exercise. Student t tests were used to compare the mean elastography measurements between participants stratified by athlete status and pre/postexercise stimulus. Analysis of variance (ANOVA) was used to compare the mean proximal, middle, and distal Achilles tendon elastography measurements. RESULTS: As seen by a greater mean shear wave velocity (8.60 ± 1.58 m/s vs 8.25 ± 1.89 m/s; P = 0.02), athletes had stiffer tendons than nonathletes. Exercise stimulus decreased average tendon shear wave velocity (8.57 ± 1.74 m/s vs 8.28 ± 1.72 m/s; P = 0.05). Tendon shear wave velocity was greatest proximally and least distally with significant differences between each region (P < 0.001). In addition, there was a significant 2-way interaction between weekly training status and foot dominance (P = 0.01). Post hoc analysis showed that this result was due to differences in tendon shear wave velocity between the dominant and nondominant lower extremity in nonathletes (7.73 ± 2.00 m/s vs 8.76 ± 1.62 m/s; P < 0.001). CONCLUSION: Female varsity collegiate athletes have higher baseline Achilles tendon stiffness as measured by SWE compared with nonathletes. Mean tendon stiffness varies based on Achilles measurement location. SWE is a quick, cost-effective, and noninvasive imaging modality that can be used to evaluate tendon stiffness and elasticity. CLINICAL RELEVANCE: SWE is an efficient and noninvasive imaging modality that can evaluate dynamic tendon stiffness and elasticity. SWE may be helpful to assess injuries in female college athletes and may play a role in risk stratification or clinical follow-up. In theory, SWE could be used to identify athletes with increased elasticity as a marker for potential risk for rupture in this population.

Updated trends in percutaneous renal arteriography among radiologists and other specialties.

PURPOSE: Prior studies have demonstrated an overall decline in percutaneous renal artery angioplasty with and without stenting from 1988 to 2009. We evaluated the recent utilization trends in percutaneous renal arteriography (PTRA) among radiologists and non-radiologist providers from 2010 to 2018. METHODS: Data from the 2010-2018 nationwide Medicare Part B fee-for-service database were used to tabulate case volumes for PTRA. Annual utilization rates per 10,000 Medicare beneficiaries were calculated and aggregated based on physician specialty: radiologists, cardiologists, vascular surgeons, general surgeons, or others. RESULTS: From 2010 to 2018, the overall utilization rate of PTRA markedly declined (-72% change; from 15.5 to 4.3 cases per 10,000 Medicare beneficiaries). Proportionally, the cardiologist share of PTRA saw the greatest decline, falling from 74% market share in 2010 (11.4/15.5 cases) to only 36% market share in 2018 (1.6/4.3 cases). The market share of PTRA performed by radiologists grew from 12% market share in 2010 (1.9/15.5 cases) to 28% in 2018 (1.2/4.3 cases); despite this, the absolute number of PTRA performed by radiologists saw a smaller decline over this period (-34%; 1.9 to 1.2 cases). CONCLUSION: The total utilization rates of PTRA in the Medicare population has continued to decline from 2010 to 2018, likely due to clinical trials suggesting limited efficacy of angioplasty and stenting in the treatment of renovascular hypertension and other factors such as declining reimbursement. The overall and per-specialty rates continue to decline, reflecting an overarching trend away from procedural management of renovascular hypertension.

Use of High-Resolution Ultrasound to Guide Alcohol Neurolysis for Chronic Pain.

BACKGROUND: The diagnosis and treatment of neuropathic pain is often clinically challenging, with many patients requiring treatments beyond oral medications. To improve our percutaneous treatments, we established a clinical pathway that utilized ultrasound (US) guidance for steroid injection and alcohol ablation for patients with painful neuropathy. OBJECTIVES: To describe a collaborative neuropathy treatment pathway developed by a neurosurgeon, pain physicians, and a sonologist, describing early clinical experiences and patient-reported outcomes. STUDY DESIGN: A retrospective case series was performed. METHODS: Patients that received percutaneous alcohol ablation with US guidance for neuropathy were identified through a retrospective review of a single provider's case log. Demographics and treatment information were collected from the electronic medical record. Patients were surveyed about their symptoms and treatment efficacy. Descriptive statistics were expressed as medians and the interquartile range ([IQR]; 25th and 75th data percentiles). Differences in the median follow-up pain scores were assessed using a Wilcoxon signed-rank test. RESULTS: Thirty-five patients underwent US-guided alcohol ablation, with the average patient receiving one treatment (range: 1 to 2), having a median duration of 4.8 months until reinjection (IQR: 2.9 to 13.1). The median number of steroid injections that individuals received before US-guided alcohol ablation was 2 (IQR: 1 to 3), and the median interval between steroid injections was 3.7 months (IQR: 2.0 to 9.6). Most (20/35 [57%]) patients responded to the survey, and the median pain scores decreased by 3 units (median: -3, IQR: -6 to 0; P < 0.001) one week following the alcohol ablation. This pain reduction remained significant at one month (P < 0.001) and one year (P = 0.002) following ablation. Most (12/20 [60%]) patients reported that alcohol ablation was more effective in improving their pain than oral pain medications. LIMITATIONS: Given the small sample size, treatment efficacy for alcohol neurolysis cannot be generalized to the broader population. CONCLUSIONS: US-guided percutaneous treatments for neuropathic pain present a growing opportunity for interprofessional collaboration between neurosurgery, clinicians who treat chronic pain, and sonologists. US can provide valuable diagnostic information and guide accurate percutaneous treatments in skilled hands. Further studies are warranted to determine whether a US-guided treatment pathway can prevent unnecessary open surgical management.