Stress Granule Assembly Disrupts Nucleocytoplasmic Transport.

Defects in nucleocytoplasmic transport have been identified as a key pathogenic event in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) mediated by a GGGGCC hexanucleotide repeat expansion in C9ORF72, the most common genetic cause of ALS/FTD. Furthermore, nucleocytoplasmic transport disruption has also been implicated in other neurodegenerative diseases with protein aggregation, suggesting a shared mechanism by which protein stress disrupts nucleocytoplasmic transport. Here, we show that cellular stress disrupts nucleocytoplasmic transport by localizing critical nucleocytoplasmic transport factors into stress granules, RNA/protein complexes that play a crucial role in ALS pathogenesis. Importantly, inhibiting stress granule assembly, such as by knocking down Ataxin-2, suppresses nucleocytoplasmic transport defects as well as neurodegeneration in C9ORF72-mediated ALS/FTD. Our findings identify a link between stress granule assembly and nucleocytoplasmic transport, two fundamental cellular processes implicated in the pathogenesis of C9ORF72-mediated ALS/FTD and other neurodegenerative diseases.

Interaction of preoperative chemoprophylaxis and tranexamic acid use does not affect transfusion in acetabular fracture surgery.

PURPOSE: While the effects of tranexamic acid (TXA) use on transfusion rates after acetabular fracture surgery are unclear, previous evidence suggests that holding deep vein thrombosis (DVT) chemoprophylaxis may improve TXA efficacy. This study examines whether holding DVT chemoprophylaxis in patients receiving TXA affects intraoperative and postoperative transfusion rates in acetabular fracture surgery. METHODS: We reviewed electronic medical records (EMR) of 305 patients who underwent open reduction and internal fixation of acetabular fractures (AO/OTA 62) and stratified patients per the following perioperative treatment: (1) no intraoperative TXA (noTXA), (2) intraoperative TXA and no preoperative DVT prophylaxis (opTXA/noDVTP), or (3) intraoperative TXA and preoperative DVT prophylaxis (opTXA/opDVTP). The primary outcomes were need for intraoperative or postoperative transfusion. Risk factors for each primary outcome were assessed using multivariable regression. RESULTS: Intraoperative or postoperative transfusion rates did not significantly differ between opTXA/opDVTP and opTXA/noDVTP groups (46.2% vs. 36%, p = 0.463; 15.4% vs. 28%, p = 0.181). Median units transfused did not differ between groups (2 ± 1 vs. 2 ± 1, p = 0.515; 2 ± 1 vs. 2 ± 0, p = 0.099). There was no association between preoperative DVT chemoprophylaxis and TXA with intraoperative or postoperative transfusions. EBL, preoperative hematocrit, and IV fluids were associated with intraoperative transfusions; age and Charlson Comorbidity Index (CCI) were associated with postoperative transfusions. CONCLUSION: Our findings suggest holding DVT prophylaxis did not alter the effect of TXA on blood loss or need for transfusion.

An External Acetabular Alignment Guide Decreases Positional Variance.

INTRODUCTION: Certain patient and operative factors limit accurate estimation of acetabular component positioning during total hip arthroplasty (THA). This study aimed to determine whether an intraoperative external alignment guide decreases variance in acetabular component positioning. MATERIALS AND METHODS: Adult patients who underwent primary THA from 2014-2018 were reviewed. Exclusion criteria were navigation, robot-assisted surgery, and inflammatory, post-traumatic, or avascular arthritis. One surgeon used an external guide while the second surgeon resected osteophytes and utilized available anatomical landmarks for positioning. Anteversion and inclination, variance, "safe zone" positioning, operative time, and hip instability were assessed. Multivariable regression models were used to examine effects on primary and secondary outcomes. RESULTS: 409 patients were included, of which 182 underwent component placement with landmarks only. Patients undergoing component placement with landmarks only were younger (p=0.002) and more often smokers (p=0.016). After multivariable risk adjustment, use of the external alignment guide was independently associated with 2.7° higher anteversion (CI: 1.6° to 3.8°) and smaller anteversion variance (-0.3, CI: -0.6 to 0.1) compared to landmarks only. It was independently associated with 3.2° higher inclination (CI: 2.0° to 4.4°), but there was no difference in inclination variance (-0.1, CI: -0.3 to 0.2). The external alignment guide was independently associated with a 14-minute shorter operative time (CI: 9.6 to 18.7) and smaller operative time variance (-0.9, CI: -1.2 to 0.6). DISCUSSION: Use of anatomical landmarks alone was associated with increased likelihood of safe zone positioning but lower precision and longer operative time. While this study was limited by lack of randomization and its retrospective nature, an acetabular positioner may be preferable to palpable or visible anatomy alone for acetabular component placement.

Drilling the cement mantle in well-fixed periprosthetic femur fractures is not associated with arthroplasty-related complications.

OBJECTIVE: To determine if screw fixation across a cement mantle is safe and effective during plate fixation of well-fixed periprosthetic femur fractures. DESIGN: Retrospective cohort study. SETTING: Academic Level I Trauma Center. PATIENTS: Twenty-eight patients with AO/OTA 32A[B1] or 32A[C] periprosthetic femur fractures treated with open reduction and internal plate and screw fixation after cemented or uncemented hip arthroplasty. INTERVENTION: Screw placement into the cement mantle during internal fixation. OUTCOME MEASUREMENTS: Primary outcome was revision arthroplasty for aseptic loosening. Secondary outcomes included radiographic evidence of aseptic loosening, infection, nonunion, implant failure, and overall reoperation rate. RESULTS: There were 28 patients who met inclusion criteria. A total of 9 patients had screws placed in the cement mantle while the remaining 19 patients had screws placed around an uncemented stem. At a mean of 3.7-year follow-up, there were no cases of revision arthroplasty or aseptic loosening in either group. There were no significant differences in rates of infection, nonunion, implant failure, or reoperation rate between patients who had screw placement into a cement mantle vs around an uncemented stem. CONCLUSION: Drilling into the cement mantle during fixation of a periprosthetic femur fracture around a well-fixed cemented hip stem appears safe and effective. When possible, surgeons can consider bicortical screws around a cemented stem, given the biomechanical advantages over unicortical screw or cerclage fixation. Larger prospective trials confirming the safety of this technique are warranted prior to routine implementation. LEVEL OF EVIDENCE: III.

Indications for cement augmentation in fixation of geriatric intertrochanteric femur fractures: a systematic review of evidence.

INTRODUCTION: Achieving durable mechanical stability in geriatric intertrochanteric proximal femur fractures remains a challenge. Concomitant poor bone quality, unstable fracture patterns, and suboptimal reduction are additional risk factors for early mechanical failure. Cement augmentation of the proximal locking screw or blade is one proposed method to augment implant anchorage. The purpose of this review is to describe the biomechanical and clinical evidence for cement augmentation of geriatric intertrochanteric fractures, and to elaborate indications for cement augmentation. METHODS: The PubMed database was searched for English language studies up to January 2021. Studies that assessed effect of calcium phosphate or methylmethacrylate cement augmentation during open reduction and internal fixation of intertrochanteric fractures were included. Studies with sample size < 5, nontraumatic or periprosthetic fractures, and nonunion or revision surgery were excluded. Study selection adhered to PRISMA criteria. RESULTS: 801 studies were identified, of which 40 met study criteria. 9 studies assessed effect of cement augmentation on fracture displacement. All but one found that cement decreased fracture displacement. 10 studies assessed effect of cement augmentation on total load or cycles to failure. All but one demonstrated that augmented implants increased this variable. Complication rates of cement augmentation during ORIF of intertrochanteric fractures ranged from 0 to 47%, while non-augmented implants ranged from 0 to 51%. Reoperation rates ranged from 0 to 11% in the cement-augmented group and 0 to 11% in the non-augmented group. Fixation failure ranged from 0 to 11% in the cement-augmented group and 0 to 20% in the non-augmented group. Nonunion ranged from 0 to 3.6% in the cement-augmented group and 0 to 34% in the non-augmented group. CONCLUSIONS: Calcium phosphate or PMMA-augmented CMN fixation of IT fractures increased construct stability and improved outcomes in biomechanical and early clinical studies. The findings of these studies suggest an important role for cement augmentation in patient populations at high risk of mechanical failure.

Tranexamic acid does not affect intraoperative blood loss or in-hospital outcomes after acetabular fracture surgery.

PURPOSE: Tranexamic acid (TXA) reduces need for transfusion in total joint arthroplasty, though findings in acetabular surgery are conflicting. We compared outcomes after acetabular fracture surgery with or without perioperative intravenous (IV) TXA administration. METHODS: We performed a retrospective review of 305 patients with acetabular fractures that underwent open reduction and internal fixation (ORIF). Eighty-nine patients received TXA, and 216 did not. The primary outcome was rates of intraoperative and postoperative allogeneic blood transfusion. RESULTS: Baseline demographics and characteristics were similar. Time from injury to surgery and estimated blood loss were comparable. Operative time (p < 0.01) and intraoperative IV fluids (p < 0.01) were greater in the non-TXA group. The proportion of patients who received blood transfusion and mean units transfused intraoperatively and postoperatively did not differ. Mean differences in preoperative and postoperative hemoglobin and hematocrit, hospital length of stay, and perioperative complications also did not differ. In a multivariable regression model, age 60-70 years, Charlson Comorbidity Index, Injury Severity Score, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approaches and intraoperative transfusion requirement were independently associated with postoperative transfusion. CONCLUSION: In this study, perioperative IV TXA did not decrease blood loss, need for transfusion, or improve in-hospital outcomes of acetabular fracture surgery. Age 60-70, CCI, ISS, and fracture patterns likely to bleed were independently associated with intraoperative transfusion. Anterior surgical approach and need for intraoperative transfusion were independently associated with postoperative transfusion. Further prospective trials are warranted to confirm these findings.

Prospectively Assigned AAST Grade versus Modified Hinchey Class and Acute Diverticulitis Outcomes.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) recently developed a classification system to standardize outcomes analyses for several emergency general surgery conditions. To highlight this system's full potential, we conducted a study integrating prospective AAST grade assignment within the electronic medical record. METHODS: Our institution integrated AAST grade assignment into our clinical workflow in July 2018. Patients with acute diverticulitis were prospectively assigned AAST grades and modified Hinchey classes at the time of surgical consultation. Support vector machine-a machine learning algorithm attuned for small sample sizes-was used to compare the associations between the two classification systems and decision to operate and incidence of complications. RESULTS: 67 patients were included (median age of 62 y, 40% male) for analysis. The decision for operative management, hospital length of stay, intensive care unit admission, and intensive care unit length of stay were associated with both increasing AAST grade and increasing modified Hinchey class (all P < 0.001). AAST grade additionally showed a correlation with complication severity (P = 0.02). Compared with modified Hinchey class, AAST grade better predicted decision to operate (88.2% versus 82.4%). CONCLUSIONS: This study showed the feasibility of electronic medical record integration to support the full potential of AAST classification system's utility as a clinical decision-making tool. Prospectively assigned AAST grade may be an accurate and pragmatic method to find associations with outcomes, yet validation requires further study.

Risk of Venous Thromboembolism Following Rhinoplasty.

BACKGROUND: Although prior studies have identified a low risk of venous thromboembolism (VTE) in rhinoplasty, these studies are limited by small samples and associated risk factors remain unknown. OBJECTIVES: The aim of this study was to discern the incidence of VTE following rhinoplasty in a large patient population through analysis of a nationwide insurance claims database. METHODS: This study involved a population-based retrospective analysis of insurance claims made by patients who underwent rhinoplasty between 2007 and 2016. Established risk factors for VTE, demographic data, procedural details, and absolute incidence of VTE were collected. RESULTS: We identified a total of 55,287 patients who underwent rhinoplasty from 2007 to 2016. Mean age [standard error of the mean] was 38.74 [0.06] years (range, 18-74 years), and 54% were female. The overall incidence of VTE was 111, of which 70 were DVT and 41 were PE. From multivariate regression analysis, previous VTE (odds ratio [OR], 52.8; 95% confidence interval [CI], 35.2-78.6; P < 0.0001), peripherally inserted central catheter (PICC)/central line placement (OR, 19.6; 95% CI, 9.8-153; P < 0.05), rib graft (OR, 4.6; 95% CI, 2.3-8.5; P < 0.0001), age 41 to 60 years (OR, 2.65; 95% CI, 1.7-4.3; P < 0.01), inflammatory bowel disease (IBD) (OR, 2.6; 95% CI, 1.0-5.5; P < 0.05), and age 61 to 74 years (OR, 2.4; 95% CI, 1.2-4.8; P < 0.05) were associated with an increased risk of VTE. CONCLUSIONS: We demonstrate a low overall incidence of VTE in rhinoplasty patients. Previous VTE, PICC/central line, advancing age, IBD, and intraoperative rib graft harvest were most strongly associated with VTE in this population cohort.

Sequential ilioinguinal or anterior intrapelvic approach with anterior approach to the hip during combined internal fixation and total hip arthroplasty for acetabular fractures.

PURPOSE: This study examined the complications and outcomes of geriatric acetabular fractures treated with open reduction internal fixation (ORIF) and total hip arthroplasty (THA) performed via combined ilioinguinal or anterior intrapelvic (AIP) approach to acetabulum and anterior approach to the hip. METHODS: Eight patients with a fracture of the acetabulum were treated at a Level I trauma center between 2010 and 2019 with combined ORIF/THA using an ilioinguinal or AIP approach for the acetabulum and a separate anterior approach to the hip. Wound dehiscence, peri-incisional skin necrosis, surgical site infection, dislocation, fracture union, acetabular component stability, and heterotopic ossification (HO) were utilized as outcome measures. Merle d'Aubigné-Postel scores were collected for the six patients that had one-year minimum follow-up. RESULTS: The mean patient age was 77 years. Four patients had anterior wall fractures, two had associated both column fractures, and two had anterior column-posterior hemitransverse fractures. All fractures healed with stable fixation of the acetabular component by 6 months. There were no instances of skin necrosis, dislocation, infection, or re-operation. One patient had a superficial wound dehiscence that resolved with local wound care. One patient developed radiographic HO but was clinically asymptomatic. The mean Merle d'Aubigné-Postel score was 15.8 (range = 14-16). CONCLUSIONS: Our small series of geriatric patients with fracture of the acetabulum treated with combined ORIF/THA, via the ilioinguinal or AIP approach with a separate anterior approach to the hip, demonstrates satisfactory outcomes with low complications after one-year of follow-up. Further research of these challenging injuries with more patients is warranted in order to determine the subset of fracture types best treated with this method and THA survivorship.

Is percutaneous screw fixation really superior to non-operative management after valgus-impacted femoral neck fracture: a retrospective cohort study.

PURPOSE: The optimal management of valgus-impacted femoral neck fractures remains controversial. Internal fixation is associated with significant rates of re-operation, while historical non-operative management strategies consisting of prolonged bed rest also resulted in patient morbidity. Our hypothesis was that screw fixation would have comparable failure rates to non-operative treatment and immediate mobilization for valgus-impacted femoral neck fractures. METHODS: Retrospective cohort at a single academic Level I trauma center of patients with valgus-impacted femoral neck fractures (AO/OTA 31-B1) treated with percutaneous screw fixation (n = 97) or non-operatively (n = 28). Operative treatment consisted of percutaneous screw fixation. Non-operative treatment consisted of early mobilization. The primary outcome was a salvage operation. Patient demographics were assessed between groups. RESULTS: More non-operatively treated patients were permitted unrestricted weight-bearing (WBAT; p = 0.002). There was no increase in complication rates or mortality, and return to previous ambulatory status was comparable between operatively and non-operatively treated patients. 35.7% (10/28) of non-operatively treated patients underwent a subsequent operation, compared to 15.5% (15/97) of patients with screw fixation (p = 0.03). Only WBAT was independently associated with treatment failure (OR 3.1, 95%CI 1.2-8.3, p =0.02). WBAT was predictive of treatment failure only in the non-operatively treated group (64.3%, 9/14 WBAT vs 8.3%, 1/12 partial, p =0.005). CONCLUSION: After controlling for weight-bearing restrictions, we found no difference in failure rates between non-operative treatment and screw fixation. Non-operative treatment with partial weight-bearing had low failure rates, comparable complication and mortality rates, and equivalent functional outcomes to operative treatment and is reasonable if a patient would like to avoid surgery and accepts the risk of subsequent arthroplasty. Overall, there were relatively high failure rates in all groups.

Trochanteric fixation nail advanced with helical blade and cement augmentation: early experience with a retrospective cohort.

Intra-articular screw cut-out is a potential complication of intertrochanteric femur fracture fixation with a cephalomedullary nail. Cement augmentation of fixation in the proximal segment offers the prospect of increased stability and fewer complications, but clinical experience with non-resorbable cement is limited. To determine the handling properties and efficacy of this new technique, we performed a retrospective propensity-matched cohort of forty-four geriatric intertrochanteric femur fractures treated with a cephalomedullary nail with (n = 11) or without (n = 33) augmentation with non-resorbable cement injected into the proximal segment. In the patients treated with cement augmentation, at minimum 3-month follow-up, there were no instances of intra-articular cut-out, and no increase in re-operation compared to conventional fixation. Cement augmentation appears to be safe and effective in geriatric intertrochanteric femur fractures to mitigate risk of cut-out.

Trochanteric osteotomy for acetabular fracture fixation: a case series and literature review.

PURPOSE: This study examined osteotomy union and heterotopic ossification (HO) after performing digastric trochanteric osteotomies during open reduction and internal fixation (ORIF) of acetabular and combined femoral head fractures. Femoral head osteonecrosis and trochanteric screw removal were secondarily assessed. METHODS: Twenty-six patients treated at a Level I trauma center, from years 2003 to 2019, who received a digastric trochanteric osteotomy during acetabular and combined femoral head fracture ORIF through a posterior surgical approach were retrospectively identified. Osteotomies were fixed with two 3.5 mm cortical lag screws. Rates of osteotomy union, HO, femoral head osteonecrosis, and trochanteric screw removal were determined. RESULTS: All osteotomies went onto union without displacement or failure of fixation. Only three (12%) patients developed severe HO (modified-Brooker class III-IV). There were no instances of femoral head osteonecrosis and only one (7%) patient required trochanteric screw removal. CONCLUSIONS: The digastric trochanteric osteotomy heals reliably with low rates of severe HO, femoral head osteonecrosis, and screw removal for soft-tissue irritation. A review of the literature is presented and found comparable findings.

Management of the posterior wall fracture in associated both column fractures of the acetabulum.

PURPOSE: The primary aim of this study was to compare clinical outcomes in patients with associated both column (ABC) acetabular fractures with fracture of the posterior wall (PW), in which the PW underwent reduction and fragment-specific fixation versus those that were treated with column fixation alone. Secondary aims were to assess PW fracture incidence and morphology, as well as to compare radiographic outcomes including fracture healing and interval displacement of the PW in those that did and did not undergo fragment-specific fixation of the PW. METHODS: This was a retrospective series of ABC acetabular fractures treated at a single Level I trauma center. Separate fractures of the PW were identified, and associated features were assessed. Associated both column fractures that underwent reduction and fragment-specific fixation of the PW where then compared to ABC fractures with PW involvement that underwent column reconstruction alone. Radiographic and clinical outcomes were compared. RESULTS: Fractures of the PW occurred in 55.7% of ABC fractures and were associated with central displacement of the femoral head. The majority of PW fractures were large and involved the acetabular roof. All PW fractures healed without displacement by 3 months, regardless of whether or not reduction and stabilization was performed. Mid-term outcomes at 1-year were similar regardless of whether or not the PW was reduced and stabilized, with regards to Tönnis grade, Merle d'Aubigné-Postel score, and conversion to total hip arthroplasty. CONCLUSION: Reduction and fragment-specific fixation of the PW component of ABC acetabular fractures did not improve outcomes in this small comparative study. Posterior wall fractures associated with ABC patterns are frequently large-sized fragments that involve the acetabular roof and are rendered stable after reconstruction of the columns.

Cephalomedullary helical blade is independently associated with less collapse in intertrochanteric femur fractures than lag screws.

OBJECTIVES: Excessive fracture site collapse and shortening in intertrochanteric femur fractures alter hip biomechanics and patient outcomes. The purpose of the study was to compare extent of collapse in cephalomedullary nails with blades or lag screws. We hypothesized that there would be no difference in collapse between helical blades and lag screws. DESIGN: Retrospective cohort study. SETTING: Single U.S. Level I Trauma Center. PATIENTS: 171 consecutive patients treated with cephalomedullary nails with either lag screw or blade for AO/OTA 31A1-3 proximal femur fractures and minimum 3-month follow-up. INTERVENTION: Lag screw or helical blade in a cephalomedullary nail. OUTCOME MEASURES: The primary outcome was fracture site collapse at 3 months. RESULTS: There was a significantly higher proportion of reverse-oblique and transverse intertrochanteric femur fractures (31-A3) in the lag screw group (15/42 vs 25/129). A3 patterns were associated with more collapse. There was significantly less collapse in the blade group (median 4.7 mm, inter-quartile range 2.5-7.8 mm) than the screw group (median 8.4 mmm, inter-quartile range 3.7-11.2 mm, p 0.006). Median collapse was no different between blades and screws when comparing stable and unstable patterns. However, blades were independently associated with 2.5 mm less collapse (95%CI - 4.2, - 0.72 mm, p 0.006) and lower likelihood of excessive collapse (> 10 mm at 3 months, OR 0.3, 95% CI 0.13-0.74, p 0.007), regardless of fracture pattern. CONCLUSIONS: Helical blades are independently associated with significantly less collapse than lag screws in intertrochanteric proximal femur fractures, after adjusting for unstable fracture patterns. In fracture patterns at risk for collapse, surgeons can consider use of a helical blade due to its favorable sliding properties compared to screws.

Costs and Outcomes of Total Joint Arthroplasty in Medicare Beneficiaries Are Not Meaningfully Associated with Industry Payments.

BACKGROUND: Prior studies have demonstrated that industry payments affect physician prescribing patterns, but their effect on orthopaedic surgical costs is unknown. This study examines the relationship between industry payments and the total costs of primary total joint arthroplasty, as well as operating room cost, length of stay, 30-day mortality, and 30-day readmission. METHODS: Open Payments data were matched across a 20% sample of Medicare-insured patients undergoing primary elective total hip arthroplasty (THA) (n = 130,872) performed by 7,539 surgeons or primary elective total knee arthroplasty (TKA) (n = 230,856) performed by 8,977 surgeons from 2013 to 2015. Patient, hospital, and surgeon-specific factors were gathered. Total and operating room costs, length of stay, mortality, and readmissions were recorded. Multivariable linear and logistic regression models were used to identify the risk-adjusted relationships between industry payments and the primary and secondary outcomes. RESULTS: In this study, 96.7% of THA surgeons and 97.4% of TKA surgeons received industry payments. After multivariable risk adjustment, for each $1,000 increase in industry payments, the total costs of THA increased by $0.50 (0.003% of total costs) and the operating room costs of THA increased by $0.20 (0.003% of total costs). Industry payments were not associated with TKA cost. Industry payments were not associated with 30-day mortality after either THA or TKA. Higher industry payments were independently associated with a marginal decrease in the length of stay for patients undergoing THA (0.0045 days per $1,000) or TKA (0.0035 days per $1,000) and a <0.1% increase in the odds of 30-day readmission after THA for every $1,000 in industry payments. The median total THA costs were $300 higher (p < 0.001), whereas the median TKA costs were $150 lower (p < 0.001), for surgeons receiving the highest 5% of industry payments. These surgical procedures were more often performed in large urban areas, in hospitals with a higher number of beds, with a higher wage index, and by more experienced surgeons and were associated with a 0.4 to 1-day shorter length of stay (p < 0.001). CONCLUSIONS: Although most arthroplasty surgeons received industry payments, a minority of surgeons received the majority of payments. Overall, arthroplasty costs and outcomes were not meaningfully impacted by industry relationships. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Do Epidural Steroid Injections Affect Outcomes and Costs in Cervical Degenerative Disease? A Retrospective MarketScan Database Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To investigate the effect of preoperative epidural steroid injection (ESI) on quality outcomes and costs in patients undergoing surgery for cervical degenerative disease. METHODS: We queried the MarketScan database, a national administrative claims dataset, to identify patients who underwent cervical degenerative surgery from 2007 to 2016. Patients under 18 and patients with history of tumor or trauma were excluded. Patients were stratified by ESI use at 3, 6, 12, 18, and 24 or more months preoperative. Propensity score matched controls for these groups were obtained. Baseline demographics, postoperative complications, reoperations, readmissions, and costs were compared via univariate and multivariate analysis. RESULTS: 97 117 patients underwent cervical degenerative surgery, of which 29 963 (30.7%) had ESI use at any time preoperatively. Overall, 90-day complication rate was not significantly different between groups. The ESI cohorts had shorter length of stay, but higher 90-day readmission and reoperation rates. ESI use was associated with higher total payments through the 2-year follow-up period. Among patients who received preoperative ESI, male sex, history of cancer, obesity, PVD, rheumatoid arthritis, nonsmokers, cervical myelopathy, BMP use, anterior approach, 90-day complication, 90-day reoperation, and 90-day readmission were independently associated with increased 90-day total cost. CONCLUSION: ESI can offer pain relief in some patients refractory to other conservative management techniques, but those who eventually undergo surgery have greater healthcare resource utilization. Certain characteristics can predispose patients who receive preoperative ESI to incur higher healthcare costs.

Operative Versus Nonoperative Management of Unstable Spine Fractures in the Elderly: Outcomes and Mortality.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess outcomes and mortality in elderly patients following unstable spine fractures depending on treatment modality. SUMMARY OF BACKGROUND DATA: Operative management of unstable spine fractures in the elderly remains controversial due to increased risk of perioperative complications. Mortality rates after operative versus nonoperative treatment of these injuries have not been well-characterized. MATERIALS AND METHODS: Patients aged above 65 with unstable spine fractures without neurologic injury from 2015 to 2021 were identified from the Clinformatics ® Data Mart (CDM) Database. Demographics, complications, and mortality were collected. Multivariable logistic regression was used to adjust for the effect of baseline characteristics on mortality following unstable fracture diagnosis. RESULTS: Of the 3688 patients included, 1330 (36.1%) underwent operative management and 2358 (63.9%) nonoperative. At baseline, nonoperative patients were older, female, had higher Elixhauser comorbidity scores, and were more likely to have a cervical fracture. Operative patients had a longer length of stay in the hospital compared with nonoperative patients (9.7 vs. 7.7 days; P <0.001). Although patients in the operative group had higher rates of readmission at 30, 60, 90, and 120 days after diagnosis ( P <0.01), they had lower mortality rates up to five years after injury. After adjusting for covariates, nonoperative patients had a 60% greater risk of mortality compared with operative patients (hazard ratio: 1.60, 95% confidence interval: 1.40-1.78, P <0.001). After propensity score matching, operative patients age 65 to 85 had greater survivorship compared with their nonoperative counterparts. CONCLUSIONS: Elderly patients with an unstable spine fracture who undergo surgery experience lower mortality rates up to five years postdiagnosis compared with patients who received nonoperative management, despite higher hospital readmission rates and an overall perioperative complication rate of 37.3%. Operating on elderly patients with unstable spine fractures may outweigh the risks and should be considered as a viable treatment option in appropriately selected patients.

Anabolic and Antiresorptive Osteoporosis Treatment: Trends, Costs, and Sequence in a Commercially Insured Population, 2003-2021.

New anabolic medications (abaloparatide and romosozumab) were recently approved for osteoporosis, and data suggest that prescribing antiresorptive medications after a course of anabolic medications offers better outcomes. This study aimed to characterize prescription trends, demographics, geographical distributions, out-of-pocket costs, and treatment sequences for anabolic and antiresorptive osteoporosis medications. Using a commercial claims database (Clinformatics Data Mart), adult patients with osteoporosis from 2003 to 2021 were retrospectively reviewed and stratified based on osteoporosis medication class. Patient demographics and socioeconomic variables, provider types, and out-of-pocket costs were collected. Multivariable regression analyses were used to identify independent predictors of receiving osteoporosis treatment. A total of 2,988,826 patients with osteoporosis were identified; 616,635 (20.6%) received treatment. Patients who were female, Hispanic or Asian, in the Western US, had higher net worth, or had greater comorbidity burden were more likely to receive osteoporosis medications. Among patients who received medication, 31,112 (5.0%) received anabolic medication; these were more likely to be younger, White patients with higher education level, net worth, and greater comorbidity burden. Providers who prescribed the most anabolic medications were rheumatologists (18.5%), endocrinologists (16.8%), and general internists (15.3%). Osteoporosis medication prescriptions increased fourfold from 2003 to 2020, whereas anabolic medication prescriptions did not increase at this rate. Median out-of-pocket costs were $17 higher for anabolic than antiresorptive medications, though costs for anabolic medications decreased significantly from 2003 to 2020 (compound annual growth rate: -0.6%). A total of 8388 (1.4%) patients tried two or more osteoporosis medications, and 0.6% followed the optimal treatment sequence. Prescription of anabolic osteoporosis medications has not kept pace with overall osteoporosis treatment, and there are socioeconomic disparities in anabolic medication prescription, potentially driven by higher median out-of-pocket costs. Although prescribing antiresorptive medications after a course of anabolic medications offers better outcomes, this treatment sequence occurred in only 0.6% of the study cohort. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Trends, payments, and costs associated with BMP use in Medicare beneficiaries undergoing spinal fusion.

BACKGROUND CONTEXT: Bone morphogenic protein (BMP) promotes bony fusion but increases costs. Recent trends in BMP use among Medicare patients have not been well-characterized. PURPOSE: To assess utilization trends, complication, payments, and costs associated with BMP use in spinal fusion in a Medicare-insured population. STUDY DESIGN/SETTING: Retrospective cohort study. PATIENT SAMPLE: Total of 316,070 patients who underwent spinal fusion in a 20% sample of Medicare-insured patients, 2006 to 2015. OUTCOME MEASURES: Utilization trends across time and geography, complications, payments, and costs. METHODS: Patients were stratified by fusion type and diagnosis. Multivariable logistic and linear regression were used to adjust for the effect of baseline characteristics on complications and total payments or cost, respectively. RESULTS: BMP was used in 60,249 cases (19.1%). BMP utilization rates decreased from 23.1% in 2006 to 12.0% in 2015, most significantly in anterior cervical (7.5%-3.1%), posterior cervical (17.0%-8.3%), and posterior lumbar fusions (31.5%-15.8%). There are significant state- and region-level geographic differences in BMP utilization. Across all years, states with the highest BMP use were Indiana (28.5%), Colorado (26.6%), and Nevada (25.7%). States with the lowest BMP use were Maine (2.3%), Vermont (8.2%), and Mississippi (10.4%). After multivariate risk adjustment, BMP use was associated with decreased overall complications in thoracic (odds ratios [OR] [95% confidence intervals [CI]): 0.89 [0.81-0.99]) and anterior lumbar fusions (OR [95% CI]: 0.89 [0.84-0.95]), as well as increased reoperation rates in anterior cervical (OR [95% CI]: 1.11 [1.04-1.19]), posterior cervical (OR (95% CI): 1.14 (1.04-1.25)), thoracic (OR (95% CI): 1.32 (1.23-1.41)), and posterior lumbar fusions (OR (95% CI): 1.11 (1.06-1.16)). BMP use was also associated with greater total costs, independent of fusion type, after multivariate risk adjustment (p<.0001). Payments, however, were comparable between groups in anterior and posterior cervical fusion with or without BMP. BMP use was associated with greater total payments in thoracic, anterior lumbar, and posterior lumbar fusions. Notably, the difference in payments was smaller than the associated cost increase in all fusion types. CONCLUSIONS: BMP use has declined across all fusion types over the last decade, after a peak in 2007. While BMP is associated with greater costs, reimbursement does not increase proportionally with BMP cost.

Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.

Cancer-associated fibroblasts (CAFs) were presumed absent in glioblastoma given the lack of brain fibroblasts. Serial trypsinization of glioblastoma specimens yielded cells with CAF morphology and single-cell transcriptomic profiles based on their lack of copy number variations (CNVs) and elevated individual cell CAF probability scores derived from the expression of 9 CAF markers and absence of 5 markers from non-CAF stromal cells sharing features with CAFs. Cells without CNVs and with high CAF probability scores were identified in single-cell RNA-Seq of 12 patient glioblastomas. Pseudotime reconstruction revealed that immature CAFs evolved into subtypes, with mature CAFs expressing actin alpha 2, smooth muscle (ACTA2). Spatial transcriptomics from 16 patient glioblastomas confirmed CAF proximity to mesenchymal glioblastoma stem cells (GSCs), endothelial cells, and M2 macrophages. CAFs were chemotactically attracted to GSCs, and CAFs enriched GSCs. We created a resource of inferred crosstalk by mapping expression of receptors to their cognate ligands, identifying PDGF and TGF-ß as mediators of GSC effects on CAFs and osteopontin and HGF as mediators of CAF-induced GSC enrichment. CAFs induced M2 macrophage polarization by producing the extra domain A (EDA) fibronectin variant that binds macrophage TLR4. Supplementing GSC-derived xenografts with CAFs enhanced in vivo tumor growth. These findings are among the first to identify glioblastoma CAFs and their GSC interactions, making them an intriguing target.