PRMT5-mediated arginine methylation of FXR1 is essential for RNA binding in cancer cells.

Emerging evidence indicates that arginine methylation promotes the stability of arginine-glycine-rich (RGG) motif-containing RNA-binding proteins (RBPs) and regulates gene expression. Here, we report that post-translational modification of FXR1 enhances the binding with mRNAs and is involved in cancer cell growth and proliferation. Independent point mutations in arginine residues of FXR1's nuclear export signal (R386 and R388) and RGG (R453, R455 and R459) domains prevent it from binding to RNAs that form G-quadruplex (G4) RNA structures. Disruption of G4-RNA structures by lithium chloride failed to bind with FXR1, indicating its preference for G4-RNA structure containing mRNAs. Furthermore, loss-of-function of PRMT5 inhibited FXR1 methylation both in vivo and in vitro, affecting FXR1 protein stability, inhibiting RNA-binding activity and cancer cell growth and proliferation. Finally, the enhanced crosslinking and immunoprecipitation (eCLIP) analyses reveal that FXR1 binds with the G4-enriched mRNA targets such as AHNAK, MAP1B, AHNAK2, HUWE1, DYNC1H1 and UBR4 and controls its mRNA expression in cancer cells. Our findings suggest that PRMT5-mediated FXR1 methylation is required for RNA/G4-RNA binding, which promotes gene expression in cancer cells. Thus, FXR1's structural characteristics and affinity for RNAs preferentially G4 regions provide new insights into the molecular mechanism of FXR1 in oral cancer cells.

Precision soft tissue balancing: grid-assisted pie-crusting in total knee arthroplasty.

Introduction: The varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release. Methods: Cadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed. Results: A total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm-7.078 ± 1.414 mm (R2 = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm (R2 = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm-4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm-25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed (R2 = 0.988). Discussion: Our results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees.

Long term cost outcomes among commercially insured patients undergoing bariatric surgical procedures.

Objective: Bariatric procedures have become safer in recent years, warranting new data on long-term costs. This study examined the impact of bariatric procedures on a person's long-term healthcare costs up to 10 years and if it differed by socio-economic status (SES). Methods: This retrospective observational study compared the downstream health care cost of patients with obesity who had undergone bariatric surgery (BS) between 2009 and 2018 to a 1:1 matched group of members with obesity but no surgery. Results: 167,764 individuals from administrative claims data with an obesity diagnosis were included; 83,882 in the BS group and 83,882 in the non-surgical group. In follow-up years 2-10, the BS group was associated with lower total medical healthcare cost compared to the non-surgical group (cost ratios ranged 0.85-0.93, p values < 0.05). When stratifying the BS group by SES quartiles, there were no significant cost differences by SES (cost ratios ranged from 0.96 to 1.05, most p values > 0.05). Conclusions: BS was associated with lower long-term follow-up medical cost and cost savings appeared similar among the SES quartiles in the BS group. The study results may help policy makers and employers in designing benefits and extending coverage for bariatric surgical procedures.

Comparative study of locking neutralization plate construct versus tension band wiring with a cannulated screw for patella fractures: experimental and finite element analysis.

Transverse patella fractures, accounting for approximately 1% of Orthopedic injuries, pose intricate challenges due to their vital role in knee mechanics. This study aimed to compare the biomechanical performance of a construct, integrating cannulated screws and an anterior locking neutralization plate, with the conventional tension band wiring technique for treating these fractures. Experimental testing and Finite Element Analysis were employed to evaluate the constructs and gain profound insights into their mechanical behavior. Sixteen cadaveric knees were prepared, and transverse patella fractures were induced at the midpoints using a saw. The plate construct and tension band wire fixation were randomly assigned to the specimens. A cyclic test evaluated the implants' durability and stability, simulating knee movement during extension and flexion. Tensile testing assessed the implants' maximum failure force after cyclic testing, while Finite Element Analysis provided detailed insights into stress distribution and deformation patterns. Statistical analysis was exclusively performed for the experimental data. Results showed the plate enhanced stability with significantly lower deformation (0.09 ± 0.12 mm) compared to wire fixation (0.77 ± 0.54 mm) after 500 cycles (p = 0.004). In tensile testing, the construct also demonstrated higher failure resistance (1359 ± 21.53 N) than wire fixation (780.1 ± 22.62N) (p = 0.007). Finite Element Analysis highlighted distinct stress patterns, validating the construct's superiority. This research presents a promising treatment approach for transverse patella fractures with potential clinical impact and future research prospects. This study presents a promising advancement in addressing the intricate challenges of transverse patella fractures, with implications for refining clinical practice. The construct's improved stability and resistance to failure offer potential benefits in postoperative management and patient outcomes.

Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis.

A novel rheumatoid arthritis (RA) synovial fluid protein, Syntenin-1, and its receptor, Syndecan-1 (SDC-1), are colocalized on RA synovial tissue endothelial cells and fibroblast-like synoviocytes (FLS). Syntenin-1 exacerbates the inflammatory landscape of endothelial cells and RA FLS by upregulating transcription of IRF1/5/7/9, IL-1ß, IL-6, and CCL2 through SDC-1 ligation and HIF1α, or mTOR activation. Mechanistically, Syntenin-1 orchestrates RA FLS and endothelial cell invasion via SDC-1 and/or mTOR signaling. In Syntenin-1 reprogrammed endothelial cells, the dynamic expression of metabolic intermediates coincides with escalated glycolysis along with unchanged oxidative factors, AMPK, PGC-1α, citrate, and inactive oxidative phosphorylation. Conversely, RA FLS rewired by Syntenin-1 displayed a modest glycolytic-ATP accompanied by a robust mitochondrial-ATP capacity. The enriched mitochondrial-ATP detected in Syntenin-1 reprogrammed RA FLS was coupled with mitochondrial fusion and fission recapitulated by escalated Mitofusin-2 and DRP1 expression. We found that VEGFR1/2 and Notch1 networks are responsible for the crosstalk between Syntenin-1 rewired endothelial cells and RA FLS, which are also represented in RA explants. Similar to RA explants, morphological and transcriptome studies authenticated the importance of VEGFR1/2, Notch1, RAPTOR, and HIF1α pathways in Syntenin-1 arthritic mice and their obstruction in SDC-1 deficient animals. Consistently, dysregulation of SDC-1, mTOR, and HIF1α negated Syntenin-1 inflammatory phenotype in RA explants, while inhibition of HIF1α impaired synovial angiogenic imprint amplified by Syntenin-1. In conclusion, since the current therapies are ineffective on Syntenin-1 and SDC-1 expression in RA synovial tissue and blood, targeting this pathway and its interconnected metabolic intermediates may provide a novel therapeutic strategy.

A Video Teaching Tool Is Effective for Training Residents in Hip Arthroplasty Templating.

Work hour restrictions imposed on orthopedic surgery residents since the early 2000s have reduced educational opportunities at the workplace and encouraged alternative strategies for teaching outside the clinical setting. Preoperative templating is essential for safe and effective total hip arthroplasty (THA) and is accurate in predicting final implants. We sought to determine the effectiveness of a video tool for teaching orthopedic residents basic THA templating skills. We developed a video-based teaching tool with instructions on proper THA templating techniques. Ten cases were selected for testing, after excluding patients with severe hip deformities and poor-quality radiographs and only retaining those with concordance between templating by the senior authors and implanted components. The study subjects included three postgraduate year 1 (PGY-1), three PGY-2, and three PGY-5 residents, and three adult reconstruction fellows (PGY-6). Templating skills were assessed before and after watching the instructional video. The evaluation included the size and positioning of femoral and acetabular components, as well as the restoration of leg length. Each templating session was repeated twice. Variance was measured to evaluate consistency in measurements. A linear mixed model and F-test were used for statistical analyses. The number of years in training significantly affected performance prior to exposure to the instructional video. Post-exposure, there was a significant improvement in the accuracy of sizing and positioning of acetabular and femoral components for PGY-1, PGY-2, and PGY-5 residents. The results achieved were comparable to PGY-6 examiners, who did not gain substantial performance benefits from the instructional video. Limb length restoration was less affected by experience or exposure to the video. Component positioning and sizing, as well as leg length discrepancy (LLD), showed a significant decrease in variance after the intervention in all study groups. Video learning is reliable in teaching invaluable skills to orthopedic surgery residents without encroaching on work hours. We conceived a concise video to train orthopedic residents to perform THA templating with proper technique and demonstrated its efficiency and reproducibility.

Genomic amplifications identified by circulating tumor DNA analysis guide prognosis in metastatic castration-resistant prostate cancer.

Purpose: Analysis of circulating tumor DNA (ctDNA) in patients with metastatic prostate cancer (mPC) provides an opportunity to identify and monitor genomic alterations during a patient's treatment course. We evaluated whether the presence of specific gene amplifications (GAs) and plasma copy number (PCN) alterations are associated with disease features. Methods: This is a single-institution retrospective study of patients with mPC who underwent ctDNA profiling using Guardant360® (Guardant Health Inc.). This test identifies single nucleotide variants (SNVs) and GAs of select genes by next-generation sequencing. A total of 155 men with mPC were studied. Patients were stratified by GA status. The Kaplan-Meier method and multivariate cox regression models were used to estimate overall survival (OS) or failure-free survival (FFS) from either the date of GA detection or the initiation of systemic therapy. The chi-square test was used to evaluate associations between clinical factors and GAs. Results: The presence of liver and/or lung metastases was associated with GAs of BRAF, CDK6, PI3KCA, and FGFR1. Survival analyses were completed on a subset of 83 patients with metastatic castration-resistant prostate cancer (mCRPC). Median OS was improved in patients with 1 GA compared to patients with ≥2 GAs, whether determined from the date of initial GA(s) detection (14.9 mo vs. 8.9 mo) or date of therapy initiation nearest to GA detection (16.7 mo vs. 9.0 mo). Patients without GAs had not reached median OS. Patients with androgen receptor (AR) GA only were also found to have better median OS compared to patients with AR GA plus at least one other additional GA (19.3 mo vs. 8.9 mo). Patients with PIK3CA GA had significantly lower median OS compared to patients with GAs that did not have a PIK3CA GA (5.9 mo vs. 16.0 mo). In patients with AR and/or MYC GA(s), median OS improved in those with reduced AR or MYC PCN during therapy compared to those without such a reduction (25.1 mo vs. 15.9 mo). Conclusions: The association of select GAs with survival provides an additional tool for assessing mCRPC prognosis and informing management. Serial monitoring of ctDNA GAs is also useful to guide prognosis and therapeutic response.

Fourth-Generation Ceramic Head Fracture in Dual Mobility Total Hip Arthroplasty: A Case Report.

Introduction: Rare cases of Biolox® delta ceramic head fractures in ceramic-on-polyethylene bearings have been reported in the literature. Virtually none of these catastrophic injuries have been documented in dual mobility constructs. Case Report: We report a case of fourth-generation delta ceramic head fracture 4.5 years after implantation in a dual mobility total hip replacement constructs as a result of a ground-level fall. The patient underwent revision arthroplasty with another delta ceramic dual mobility construct and was able to return to work in custodial services 2 weeks after the revision procedure. Conclusion: In summary, we presented an extremely uncommon case of a fractured fourth generation, Biolox® delta ceramic head in a dual mobility total hip arthroplasty (THA), as a result of a ground-level fall. The patient underwent successful revision surgery to another dual mobility delta ceramic THA. Despite substantial advances in ceramic materials, catastrophic failure of 4th generation ceramic head components can still occur even in dual mobility constructs and require revision arthroplasty surgery.

The ubiquitin E3 ligase ARIH1 regulates hnRNP E1 protein stability, EMT and breast cancer progression.

The epithelial to mesenchymal transition (EMT), a process that is aberrantly activated in cancer and facilitates metastasis to distant organs, requires coordinated transcriptional and post-transcriptional control of gene expression. The tumor-suppressive RNA binding protein, hnRNP-E1, regulates splicing and translation of EMT-associated transcripts and it is thought that it plays a major role in the control of epithelial cell plasticity during cancer progression. We have utilized yeast 2 hybrid screening to identify novel hnRNP-E1 interactors that play a role in regulating hnRNP-E1; this approach led to the identification of the E3 ubiquitin ligase ARIH1. Here, we demonstrate that hnRNP-E1 protein stability is increased upon ARIH1 silencing, whereas, overexpression of ARIH1 leads to a reduction in hnRNP-E1. Reduced ubiquitination of hnRNP-E1 detected in ARIH1 knockdown (KD) cells compared to control suggests a role for ARIH1 in hnRNP-E1 degradation. The identification of hnRNP-E1 as a candidate substrate of ARIH1 led to the characterization of a novel function for this ubiquitin ligase in EMT induction and cancer progression. We demonstrate a delayed induction of EMT and reduced invasion in mammary epithelial cells silenced for ARIH1. Conversely, ARIH1 overexpression promoted EMT induction and invasion. ARIH1 silencing in breast cancer cells significantly attenuated cancer cell stemness in vitro and tumor formation in vivo. Finally, we utilized miniTurboID proximity labeling to identify novel ARIH1 interactors that may contribute to ARIH1's function in EMT induction and cancer progression.

Heterogeneous nuclear ribonucleoprotein E1 binds polycytosine DNA and monitors genome integrity.

Heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) is a tumor suppressor protein that binds site- and structure-specifically to RNA sequences to regulate mRNA stability, facilitate alternative splicing, and suppress protein translation on several metastasis-associated mRNAs. Here, we show that hnRNP E1 binds polycytosine-rich DNA tracts present throughout the genome, including those at promoters of several oncogenes and telomeres and monitors genome integrity. It binds DNA in a site- and structure-specific manner. hnRNP E1-knockdown cells displayed increased DNA damage signals including γ-H2AX at its binding sites and also showed increased mutations. UV and hydroxyurea treatment of hnRNP E1-knockdown cells exacerbated the basal DNA damage signals with increased cell cycle arrest, activation of checkpoint proteins, and monoubiquitination of proliferating cell nuclear antigen despite no changes in deubiquitinating enzymes. DNA damage caused by genotoxin treatment localized to hnRNP E1 binding sites. Our work suggests that hnRNP E1 facilitates functions of DNA integrity proteins at polycytosine tracts and monitors DNA integrity at these sites.

An Update on Multimodal Pain Management After Total Joint Arthroplasty.

➤: Multimodal analgesia has become the standard of care for total joint arthroplasty as it provides superior analgesia with fewer side effects than opioid-only protocols. ➤: Systemic medications, including nonsteroidal anti-inflammatory drugs, acetaminophen, corticosteroids, and gabapentinoids, and local anesthetics via local infiltration analgesia and peripheral nerve blocks, are the foundation of multimodal analgesia in total joint arthroplasty. ➤: Ideally, multimodal analgesia should begin preoperatively and continue throughout the perioperative period and beyond discharge. ➤: There is insufficient evidence to support the routine use of intravenous acetaminophen or liposomal bupivacaine as part of multimodal analgesia protocols.

Optimizing the vertical position of the brace thoracic pad: Apical rib or apical vertebra?

INTRODUCTION: The vertical position of the thoracic pad is a subject of controversy in brace design. Traditional recommendations dictate a maximal force applied at the level of the apical rib, about 2 levels below the apical vertebra. We sought to evaluate the optimal vertical position of the brace thoracic pad using fulcrum bending radiographs. HYPOTHESIS: A lateral force applied at the apical vertebra of a thoracic curve is more efficient at correcting coronal deformity than a force placed the apical rib. PATIENTS AND METHODS: In this prospective study, we recruited patients presenting with adolescent idiopathic scoliosis (AIS) and Risser stage 0-2 over a period of 12 months. Patients with a history of spine or thoracic surgery were excluded. Two fulcrum bending radiographs were performed for each patient: one with the center of the fulcrum placed under the most lateral part of the apical rib and another with the fulcrum centered below the apical vertebra. Cobb angles were measured on each fulcrum radiograph and compared using a paired t test. RESULTS: Fifty-two patients were included, with a mean age of 12.4 years and mean thoracic Cobb angle of 39.4˚. Placing a fulcrum under the apical vertebra reduced the Cobb angle to a mean of 11.5˚, which was significantly lower than a fulcrum placed under the apical rib (14.3˚, p=0.001). This corresponded to a 20% relative loss in the absolute correction angle when placing the fulcrum under the apical rib. The difference between the 2 Cobb angles was not significantly correlated to patient age (p=0.896) or curve apex (p=0.813). DISCUSSION: This is the first clinical study addressing the vertical position of the thoracic pad in braces for AIS. A lateral force applied at the level of the apical vertebra was significantly more efficient at reducing thoracic curve deformities than one applied at the apical rib. Our results provide clinical support to finite element studies that refute traditional recommendations of brace design, advocating for a revision of these guidelines to optimize non-operative treatment of AIS. LEVEL OF EVIDENCE: II, prospective comparative study.

Compartment Syndrome of the Hand: A Rare Sequela of Transradial Cardiac Catheterization.

A 64-year-old man who underwent percutaneous coronary intervention via right radial artery access reported right-hand pain and swelling 2 hours after the procedure. He had developed compartment syndrome of the hand, specifically with muscular compromise of the thenar compartment but with no involvement of the forearm. He underwent emergency right-hand compartment release and carpal tunnel release, followed by an uneventful postoperative course. In addition to our patient's case, we discuss compartment syndrome of the hand and related issues.

Total joint arthroplasty in cancer patients.

Increasing numbers of total joint arthroplasty (TJA) patients have a history, or an active diagnosis, of cancer. We aimed to evaluate the risk of early postoperative complications in these patients. In our series, a history of malignancy was associated with an elevated risk of ischemic cardiac events and postoperative deep vein thrombosis (DVT), while active malignancy was associated with increased respiratory and renal complications, hematoma/seroma formation and early postoperative mortality. Both groups presented increased rates of overall in-hospital complications. Patients with bone metastasis to the hip demonstrated increased DVT and 90-day mortality rates. Cancer patients have increased morbidity and mortality after TJA and should undergo comprehensive medical optimization and adapted thromboprophylaxis.

Cryptococcal aortitis presenting as a symptomatic abdominal aortic aneurysm.

We report a case of cryptococcal aortitis in a 59-year-old man presenting as a symptomatic suprarenal abdominal aortic aneurysm (AAA). The patient underwent repair of his aneurysm using a rifampin-soaked graft with omental wrapping. Intraoperative Gram stains showed yeast organisms, the cultures eventually grew Cryptococcus neoformans with results available 43 days postoperatively. He was started on antifungal therapy intraoperatively and will be on lifelong antifungal treatment. Our case is the first report of cryptoccocal aortitis presenting as a symptomatic AAA; the diagnosis of a true mycotic aneurysm was made intraoperatively.

Fewer postoperative fevers: an unexpected benefit of multimodal pain management?

BACKGROUND: Elevated temperatures after total joint arthroplasty (TJA) are common and can be a source of anxiety both for the patient and the surgical team. Although such fevers rarely are caused by acute infection, many patients are subjected to extensive testing for elevated body temperature after surgery. We recently implemented a multimodal pain management regimen for TJA, which includes acetaminophen, pregabalin, and celecoxib or toradol, and because some of these medications have antipyrexic properties, it was speculated that this protocol might influence the frequency of postoperative pyrexia. QUESTIONS/PURPOSES: The purpose of this study was to determine whether patients treated under this protocol were less likely to exhibit postoperative fever after primary TJA, compared with a historical control group, and whether they were less likely to receive postoperative testing as part of a fever workup. METHODS: We compared 1484 primary TJAs in which pain was controlled primarily with opioid-based relief from July 2004 to December 2006 with 2417 procedures from July 2009 to December 2011 during which time multimodal agents were used. The same three surgeons were responsible for care in both of these cohorts. Oral temperature readings in the first 5 postoperative days (POD) were drawn from a review of medical records, which also were evaluated for fever workup tests, including urinalysis, urine culture, chest radiograph, and blood culture. Fever was defined by the presence of a temperature measurement over 38.5 °C. Patients having preoperative fever or postoperative fever starting later than POD 5 were excluded. Before surgery, there were no differences between the groups' temperature measurements. RESULTS: Fewer patients developed fever in the multimodal analgesia group than in the control group (5% versus 25%, p < 0.001). Furthermore, fewer patients underwent workup for fever in the multimodal analgesia cohort (1.8% of patients undergoing 155 individual tests) compared with the control cohort (9.8% of patients undergoing 247 individual tests; p < 0.001). CONCLUSIONS: In addition to fewer adverse effects and better pain control, the multimodal analgesia protocol has the hidden benefit of dampening the temperature response to the surgical insult of TJA. The decreased rate of postoperative fever avoids unnecessary anxiety for the patient and the treating team and reduces healthcare resource use occasioned by working up postoperative fever. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Periprosthetic joint infection increases the risk of one-year mortality.

BACKGROUND: Periprosthetic joint infection continues to potentially complicate an otherwise successful joint replacement. The treatment of this infection often requires multiple surgical procedures associated with increased complications and morbidity. This study examined the relationship between periprosthetic joint infection and mortality and aimed to determine the effect of periprosthetic joint infection on mortality and any predictors of mortality in patients with periprosthetic joint infection. METHODS: Four hundred and thirty-six patients with at least one surgical intervention secondary to confirmed periprosthetic joint infection were compared with 2342 patients undergoing revision arthroplasty for aseptic failure. The incidence of mortality at thirty days, ninety days, one year, two years, and five years after surgery was assessed. Multivariate analysis was used to assess periprosthetic joint infection as an independent predictor of mortality. In the periprosthetic joint infection population, variables investigated as potential risk factors for mortality were evaluated. RESULTS: Mortality was significantly greater (p < 0.001) in patients with periprosthetic joint infection compared with those undergoing aseptic revision arthroplasty at ninety days (3.7% versus 0.8%), one year (10.6% versus 2.0%), two years (13.6% versus 3.9%), and five years (25.9% versus 12.9%). After controlling for age, sex, ethnicity, number of procedures, involved joint, body mass index, and Charlson Comorbidity Index, revision arthroplasty for periprosthetic joint infection was associated with a fivefold increase in mortality compared with revision arthroplasty for aseptic failures. In the periprosthetic joint infection population, independent predictors of mortality included increasing age, higher Charlson Comorbidity Index, history of stroke, polymicrobial infections, and cardiac disease. CONCLUSIONS: Although it is well known that periprosthetic joint infection is a devastating complication that severely limits joint function and is consistently difficult to eradicate, surgeons must also be cognizant of the systemic impact of periprosthetic joint infection and its major influence on fatal outcome in patients.

Predictors of operative mortality following major lower extremity amputations using the National Surgical Quality Improvement Program public use data.

BACKGROUND: The most definitive outcome data on lower extremity amputation (LEA) comes from the Veterans Administration (VA) system. Because of the unique nature of VA patients (more chronic disease, greater functional disability, and lower socioeconomic status), it is not clear these results can be generalized to the private sector. This study was undertaken to determine the short-term outcome of LEA in private sector patients and to define predictors of operative mortality. METHODS: After Institutional Review Board approval and under the National Surgical Quality Improvement Program public use agreement, a data set of LEA based on Current Procedural Terminology coding was assembled for the years 2005 to 2008. Patient demographics, comorbidities, and laboratory values were compiled and linked to operative mortality. Dichotomous variables were analyzed using χ(2) test with odds ratios (ORs) and continuous variables with Student t-test. Predictive modeling was done using stepwise logistic regression. Data were analyzed in SPSS. RESULTS: A total of 6839 patients underwent 4001 amputations below-knee (BK) and 2838 above-knee (AK) with a 9.1% operative mortality (6.5% BK, 12.7% AK; P < .001). Age >60 years (OR, 2.4; 95% confidence interval [CI], 1.9-2.9), white race (OR, 1.2; 95% CI, 1.0-1.4), and American Society of Anesthesiologists classification (II, 2.3% vs IV, 13.8%) were significant predictors of mortality. Preoperative functional status (20% for totally dependent vs 4.3% for independent), renal failure (OR, 2.3; 95% CI, 1.7-3.2), and congestive heart failure (OR, 2.6; 95% CI, 2.1-3.3) also predicted death. Postoperative complications associated with mortality included pneumonia (OR, 5.4; 95% CI, 4.1-7.0), ventilator dependence (OR, 5.1; 95% CI, 3.8-6.8), and need for transfusion (OR, 3.7; 95% CI, 2.0-6.7). Hispanic and African-American race (OR, 0.6; 95% CI, 0.4-0.9 and OR, 0.8; 95% CI, 0.7-1), history of peripheral arterial disease (OR, 0.6; 95% CI, 0.5-0.8), and smoking (OR, 0.5; 95% CI, 0.4-0.7) were protective (all ORs had P values < .001). CONCLUSIONS: The mortality of LEA in private sector patients remains high, with risk factors similar to those identified in previous studies of VA patients. These results should serve as a benchmark for future attempts to improve the outcome of LEA and serve to improve patient and family counseling.