Comparisons of Procedures Performed in Training vs in Early Practice by Orthopaedic Trauma Surgeons.

INTRODUCTION: The Orthopaedic Trauma Association (OTA) has maintained an accreditation process of orthopaedic trauma fellowships with various requirements including an annually reviewed list of qualifying trauma cases in the form of American Medical Association Current Procedural Terminology (CPT) codes. The correlation between these established and monitored CPTs and the actual practices of orthopaedic trauma surgeons has not been studied. METHODS: American Board of Orthopaedic Surgery part II case logs (trauma subspecialty) (2012 to 2018) were compared with OTA fellowship case logs (2015 to 2019). Case logs from 447 surgeons and 166 trauma fellowship programs were compared. Four CPT code categories were defined: complex trauma (OTA required CPT codes, excluding Accreditation Council for Graduate Medical Education [ACGME] orthopaedic residency requirements), general trauma (ACGME residency required trauma codes), general orthopaedics (nontrauma ACGME residency requirements), and others (codes not included in residency or trauma fellowship requirements). RESULTS: OTA fellows performed a higher median percentage of complex trauma compared with American Board of Orthopaedic Surgery candidates (34% vs. 21%, P < 0.001): Both cohorts performed a similar percentage of general trauma (23%). OTA fellows performed more general orthopaedics (40% vs. 1%, P < 0.001). Several OTA required codes were performed infrequently (0 to 3 during board collection) by most surgeons, and several procedures are being performed that are not included in current CPT code requirements. DISCUSSION: Early-career traumatologists are performing orthopaedic trauma procedures they were trained on during residency and fellowship, with varying complexity. Trauma fellows perform a higher percentage of complex trauma compared with early-career trauma surgeons. Continued surveillance is necessary such that educational improvements can be made to maximize the quality of trauma fellowship education. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Comparison of clinical and radiographic outcomes of arthroscopic-assisted percutaneous fixation versus open reduction internal fixation of lateral tibial plateau fractures.

PURPOSE: Treatment for tibial plateau fractures continues to evolve but maintains primary objectives of anatomic reduction of the joint line and a rapid recovery course. Arthroscopic-assisted percutaneous fixation (AAPF) has been introduced as an alternative to traditional open reduction internal fixation (ORIF). The purpose of the study is to compare clinical and radiographic outcomes in patients with low-energy Schatzker type I-III tibial plateau fractures treated with AAPF versus ORIF. METHODS: A retrospective chart review was performed at a level 1 trauma centre to compare outcomes of 120 patients (57 AAPF, 63 ORIF) with low-energy lateral Schatzker type I-III tibial plateau fractures who underwent tibial plateau fixation between 2009 and 2018. Demographic information, injury characteristics, and surgical treatment were recorded. The main outcome measurements included reduction step-off, joint space narrowing, time to weight bearing, and implant removal. RESULTS: There was no difference in age, gender distribution, BMI, ASA, Schatzker classification distribution, initial displacement, blood loss, and reduction step-off between the two groups (p > 0.05). Shorter tourniquet time (74.1 ± 21.7 vs 100.0 ± 21.0 min; p < 0.001), shorter time to full weight bearing (47.8 ± 15.2 vs. 69.1 ± 17.2 days; p < 0.001), and lower rate of joint space narrowing (3.5% vs. 28.6% with more than 1 mm, p < 0.001) were associated with the AAPF cohort, with no difference in pain, knee range of motion, or implant removal rate between the two cohorts. CONCLUSION: AAPF may be a viable alternative to ORIF for the management of low-energy tibial plateau fractures with outcomes not inferior compared to the traditional ORIF method.

Results of Implementation of Amyloidosis Screening for Patients Undergoing Carpal Tunnel Release.

PURPOSE: Many patients with amyloidosis undergo carpal tunnel release (CTR) before amyloidosis diagnosis and before developing cardiac or other serious disease manifestations. The purposes of this study were to examine if our patient population had a similar prevalence of positive amyloidosis diagnoses to that in prior studies and to describe the results of implementing a screening program for amyloidosis. METHODS: We retrospectively reviewed the biopsy results and subsequent interventions for all patients who underwent screening tenosynovial biopsy during CTR from March 2020 through December 2021. Amyloid screening was offered to patients who met the criteria for increased risk of disease using an appropriateness screening algorithm. RESULTS: Seventy-five (48%) of 156 patients who underwent CTR met the eligibility criteria for amyloidosis testing. Of the 62 patients who agreed to undergo tenosynovial biopsy, 14 had amyloid-positive biopsy specimens (10 men and 4 women). All patients with positive tenosynovial biopsies had bilateral carpal tunnel syndrome and wild-type transthyretin amyloid subtype. One patient was diagnosed and started treatment for otherwise asymptomatic cardiac amyloidosis. CONCLUSIONS: The incidence of amyloid-positive tenosynovial biopsy results from CTR was 22.5% in patients using the criteria from an appropriateness screening algorithm, which was higher than previously reported. Implementation of a screening program for patients undergoing CTR requires a multidisciplinary approach and may result in early diagnosis and lifesaving interventions for patients with amyloidosis. TYPE OF STUDY/LEVEL OF EVIDENCE: Differential diagnosis/symptom prevalence study, II.

Outcomes of arthroscopic-assisted lateral tibial plateau fixation: a systematic review.

PURPOSE: The purpose of this study is to evaluate and summarize the current literature on outcomes of arthroscopic-assisted tibial plateau fixation (AATPF) when applied for only lateral tibial plateau fractures. METHODS: A comprehensive search of nine databases was conducted: ClinicalTrials.gov, Cochrane Library via Wiley, Embase and MEDLINE via Ovid, Global Index Medicus, PubMed, Scopus, SPORTDiscus via EBSCO, and Web of Science Core Collection. The study was performed in concordance with PRISMA guidelines. Studies eligible for inclusions included Schatzker I-III lateral tibial plateau fractures with a minimum of 6-month follow-up. Data extraction was performed by two authors independently using a predesigned form. RESULTS: A total of 17 studies, 7 prospective and 10 retrospective, including 565 patients (age 15-82 years old) treated with AATPF were included in this review with follow-up ranging from 6 to 138 months. All 10 studies that used categorical functional outcomes demonstrated excellent/very good or good outcomes in > 90% of patients. When compared to patients managed with the traditional open reduction internal fixation (ORIF), patients treated with AATPF had statistically significantly better range of motion mean difference [5.21° (95% CI - 2.50 to 12.92, p < 0.0001)], lower blood loss [66.19 mL (95% confidence interval (CI) 32.54-99.84 mL, p < 0.0001)], shorter hospital stay [- 1.41 days (95% CI - 3.39 to 0.58 days, p < 0.0001)], better Hospital Special Surgery score [11.31 (95% CI 6.49-16.12, p < 0.0001)], and higher Rasmussen radiographic score [1.26 (95% CI - 0.72 to 3.23, p < 0.0001)]. CONCLUSION: AATPF is a promising treatment of lateral tibial plateau fractures with some advantages over the traditional ORIF. LEVEL OF EVIDENCE: Therapeutic Level III.

The influence of viral respiratory season on perioperative outcomes in patients undergoing spinal fusion for neuromuscular scoliosis.

PURPOSE: Respiratory complications are common following neuromuscular scoliosis (NMS) spinal fusion. Concern exists regarding the safety to perform complicated procedures in winter months when viral respiratory illness is common. The purpose of this study was to compare perioperative outcomes in children with NMS undergoing spinal fusion during peak (November-March) or non-peak (April-October) viral season. METHODS: The Health Care and Utilization Project (HCUP) Kids' inpatient database (KID) from 2006 to 2012 was reviewed. Children 20 years or younger who underwent spinal fusion for NMS were included. Patients were grouped by date of surgery during peak or non-peak viral season. Continuous variables were compared using t tests and categorical variables were compared using the Rao-Scott Chi-square test. Weighted logistic regression models were performed. RESULTS: This study identified 5082 records, including 1711 and 3371 patients who had surgery in peak and non-peak viral seasons, respectively. Patients who had spinal fusion during peak viral season were less likely to experience respiratory failure (p = 0.0008) and did not demonstrate an increased incidence of aspiration pneumonia (p = 0.26), respiratory complication (p = 0.43), or mortality (p = 0.68). Respiratory failure was associated with younger age (p = 0.0031), the presence of a tracheostomy (p < 0.0001), and the number of chronic conditions (p < 0.0001). Higher number of chronic medical conditions (mean of 5.0) was associated with an increased risk of in-hospital mortality (p < 0.0001), aspiration pneumonia (p = 0.0009), and respiratory failure (p < 0.0001). CONCLUSION: Spinal fusion for NMS during peak viral season has a lower risk of respiratory failure without an increase in mortality or other complications compared to during non-peak viral season.

Complications in the 2-Year Postoperative Period Following Pediatric Syndactyly Release.

PURPOSE: Syndactyly surgical release is one of the most common congenital hand surgeries performed by pediatric hand surgeons. The purpose of our study was to evaluate the complications associated with syndactyly release and determine factors that correlate with higher complication rates within the 2-year postoperative period. METHODS: A retrospective chart review was completed for patients who underwent syndactyly release at a single pediatric center between 2005 and 2018. Patients were included if they had a diagnosis of syndactyly and underwent surgical release, and excluded for a diagnosis of cleft hand, incomplete surgical documentation, surgery performed at an outside institution, or follow-up care that did not extend beyond the first postoperative visit. Complications were classified using the Clavien-Dindo (CD) system. RESULTS: Fifty-nine patients met the inclusion criteria, which included 143 webs released in 85 surgeries. A total of 27 complications occurred for the 85 surgeries performed. The severity of complications was CD grade I or II in 23% of surgeries, most commonly unplanned cast changes, and CD grade III in 8% of surgeries. No CD grade IV or V complications occurred. The CD grade III complications included 6 reoperations. The complication rate was higher when performing >1 syndactyly release per surgery. It also was higher for patients undergoing >1 surgical event. Rates of complication per surgery were similar between patients with multiple surgeries compared with those with a single surgery. Concomitant diagnoses and complexity of syndactyly was not associated with a higher complication rate. CONCLUSIONS: Syndactyly release was associated with a complication rate of 31% per surgical event with 44% of these complications related to unplanned cast changes and 8% of complications that required admission or reoperation. Risk factors for complications following syndactyly release include >1web operated on per surgery and undergoing >1 surgical event. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognosis IV.

Glucocorticoid-Induced Bone Loss: Dietary Supplementation Recommendations to Reduce the Risk for Osteoporosis and Osteoporotic Fractures.

Glucocorticoids (GCs) are among the most widely prescribed medications in dermatologic practice. Although considered generally safe and efficacious, prolonged use and high dosing regimens may precipitate GC-induced osteoporosis, which contributes to an increased risk for fragility fractures. Dermatologists using and prescribing GCs must be aware of the risk for GC-induced osteoporosis. This review details the risks for osteoporosis and osteoporotic (OP) fractures in the setting of topical, intralesional, intramuscular, and systemic GC treatment, as well as nutritional supplementation recommendations that may reduce the risk of these adverse effects.

Motorized Plate Lengthening of the Femur in Children: A Preliminary Report.

BACKGROUND: Limb lengthening by distraction osteogenesis can be performed with motorized internal devices, but intramedullary implants risk avascular necrosis of the femoral head in young children. A method of internal limb lengthening using a motorized expandable plate has been developed and preliminary results are presented. METHODS: Seven skeletally immature patients (ages 2.7 to 9.7 y) with congenital femoral deficiencies underwent femoral lengthening with the use of a magnetic expandable plate. Surgical details, lengthening parameters, Limb Lengthening and Reconstruction Society-Angular deformity, Infection, Motion index, and complications were reviewed and classified according to the modified Clavien-Dindo system. RESULTS: An average lengthening was 4.1 cm (range, 3.3 to 4.4 cm) comprising 18% of initial femoral segment length (range, 14% to 21%). The average lengthening phase was 50.2 days (range, 40 to 57 d) and weight-bearing was initiated at an average of 13 weeks from surgery (range, 8 to 18 wk). Limb deformities and length discrepancies were of moderate complexity, with an Limb Lengthening and Reconstruction Society-Angular deformity, Infection, Motion score of 6.57 (range, 6 to 7). Complication rates were comparable to previously reported methods of femoral lengthening. One patient underwent reoperation for patellar instability and 1 patient experienced radiographic hip subluxation which was observed. Small magnitude varus was observed in regenerate in 3 of 7 cases, none requiring treatment. Preoperative planning consisted of careful localization of the corticotomy site, acute deformity correction at the lengthening site in 3 cases, and implant orientation. CONCLUSIONS: Limb lengthening with motorized internal plates is feasible for young children with congenital femoral deficiency for whom intramedullary lengthening is unsafe or if external fixation is to be avoided. However, the fundamental principles of distraction osteogenesis and risks of lengthening for congenital discrepancies remain unchanged. Specific considerations herein include: careful planning of implant length and positioning, adjacent joint protection with adjunctive means, and mitigating deformity of the regenerate during distraction. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Park-Harris Lines.

Park-Harris lines are radiographically apparent linear opacities that occur in a metaphyseal bone in proximity to a physis. Lines correspond to a temporary interruption of the normally ossifying physis with a sclerotic line corresponding to transversely oriented trabeculae. They were first appreciated in the long bones of diabetic children and have since been described in various metabolic, endocrinologic, infectious, neoplastic, and posttraumatic conditions as well as in response to systemic medications. Park-Harris lines are clinically useful in demarcating notable events in whole-body or individual bone development, in tracking longitudinal growth, or in assessing physeal arrest and responses to its treatment. There remains controversy about whether these lines are pathologic or a component of physiologic development and whether they constitute true "growth arrest" or rather "growth recovery." In this review, the history, pathophysiology, imaging, and clinical use of Park-Harris lines as well as an anthropological perspective on their utility for studying illness, nutrition, and historical living conditions over time are discussed.

Does Inpatient Mobilization Predict 1-Year Mortality After Femoral Neck Fracture Treated With Hemiarthroplasty?

OBJECTIVE: To determine whether inpatient mobilization (defined as ambulation before hospital discharge) is associated with 1-year mortality and 90-day hospital readmission in patients treated with a hip hemiarthroplasty for a femoral neck fracture. DESIGN: Retrospective case-control. SETTING: Academic Level 1 trauma center. PATIENTS/PARTICIPANTS: Two hundred twelve consecutive femoral neck fractures were treated with hip hemiarthroplasties with a minimum of 1 year of follow-up. INTERVENTION: All study patients were treated with a hip hemiarthroplasty and weight-bearing as tolerated postoperative day 1. Patients were prescribed daily physical therapy with the goal of mobilization before discharge from hospital. MAIN OUTCOME MEASURES: Mortality at 1 year; hospital readmission within 90 days. RESULTS: Two hundred twelve patients were included in the study. One-year mortality was 29%. One hundred thirty-two (62%) patients were able to ambulate before hospital discharge. Ambulation with physical therapy before discharge from hospital was a significant predictor of 1-year mortality when compared with patients who were unable to ambulate (hazard ratio 0.57; 95% confidence interval, 0.34-0.94; P = 0.03), which equates to 43% reduction in risk of mortality. There was no difference in the 90-day readmission rates for ambulatory versus nonambulatory patients. CONCLUSIONS: Ambulation with physical therapy before discharge reduced the risk of 1-year mortality by 43%, without an effect on 90-day readmission. Sixty-two percentage of our cohort was able to ambulate before discharge. Future investigations are warranted to further identify those patients at heightened risk of mortality and readmission and the role of early rehabilitation in recovery. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Osteoporotic Fractures: What Orthopaedic Surgeons Can Do to Prevent the Next Fall and the Next Fracture?

SUMMARY: Falls are the leading cause of injuries for geriatric patients, causing significant morbidity and mortality. Orthopaedic surgeons should take an active role in decreasing patient falls, improving patient bone health, and initiate care to prevent subsequent fracture. In this manuscript, we outline 5 areas for orthopaedic surgeons to intervene and prevent the next fall: (1) patient education; (2) modifying environment/home safety measures; (3) medical fall risk assessment; (4) bone health evaluation and optimization; and (5) physical/occupational therapy.

Safety of a Noninvasive Expandable Electromagnetic Prosthesis with an In Situ Ventricular Assist Device: A Case Report.

CASE: An 8-year-old girl was diagnosed with osteosarcoma of the distal femur. She underwent chemotherapy and wide resection with implantation of a noninvasive electromagnetic expandable distal femur prosthesis. Ninety-three days after chemotherapy, she developed anthracycline-induced cardiomyopathy with heart failure for which a ventricular assist device was placed. Device compatibility was tested, and she was successfully lengthened. CONCLUSION: Expandable prostheses allow limb length maintenance in skeletally immature patients who undergo limb salvage. Chemotherapy for osteosarcoma involves anthracyclines with a dose-dependent side effect of cardiotoxicity. Patients can be successfully and safely lengthened with expandable electromagnetic prostheses with in situ ventricular assist devices.

Management of Civilian Low-Velocity Gunshot Injuries to an Extremity.

➤: Despite an increasing rate of civilian low-velocity gunshot injuries, there remains a lack of evidence-based treatment standards. ➤: Most low-velocity gunshot-induced fractures of the extremity can be managed similarly to non-gunshot-induced fractures, with the goals of restoring function and minimizing complications. ➤: There are a limited number of high-quality studies to support the use of prophylactic antibiotics for nonoperatively treated gunshot wounds. ➤: Intra-articular retained bullets should be removed, while prophylactic irrigation and debridement for a transarticular bullet is not routinely warranted for infection prevention. ➤: Much of the literature on low-velocity gunshot wounds is Level-III or IV evidence, warranting the need for higher-powered, randomized, prospective investigations.

Advanced Templating for Total Shoulder Arthroplasty.

¼: Longitudinal clinical and radiographic success of total shoulder arthroplasty (TSA) is critically dependent on optimal glenoid component position. ¼: Historically, preoperative templating utilized radiographs with commercially produced overlay implant templates and a basic understanding of glenoid morphology. ¼: The advent of 3-dimensional imaging and templating has achieved more accurate and precise pathologic glenoid interrogation and glenoid implant positioning than historical 2-dimensional imaging. ¼: Advanced templating allows for the understanding of unique patient morphology, the recognition and anticipation of potential operative challenges, and the prediction of implant limitations, and it provides a method for preoperatively addressing abnormal glenoid morphology. ¼: Synergistic software, implants, and instrumentation have emerged with the aim of improving the accuracy of glenoid component implantation. Additional studies are warranted to determine the ultimate efficacy and cost-effectiveness of these technologies, as well as the potential for improvements in TSA outcomes.

Arthroscopic Transosseous Repair of a Medial Meniscal Posterior-Root Tear.

Meniscal root tears are soft-tissue and/or osseous injuries characterized by an avulsion of, or tear within 1 cm of, the native meniscal insertion1. These injuries account for 10% to 21% of all meniscal tears, affecting nearly 100,000 patients annually2. Medial meniscal posterior-root tears (MMPRTs) expose the tibiofemoral joint to supraphysiologic contact pressure, decreased contact area, and altered knee kinematics similar to a total meniscectomy3. This injury predisposes the patient to exceedingly high rates of osteoarthritis and total knee arthroplasty secondary to an inability to resist hoop stress4. The arthroscopic transosseous repair of an MMPRT is described in the present article. Description: (1) Preoperative evaluation, including patient history, examination, and imaging (i.e., radiographs and magnetic resonance imaging). (2) Preparation and positioning. The patient is placed in the supine position, and anteromedial and anterolateral portals are created. (3) Placement of sutures. Two simple cinch sutures are placed into the posterior horn, within approximately 5 mm of each other. (4) Footprint decortication. Remove articular cartilage from the native root insertion site. (5) Drilling of the transosseous tibial tunnel. Introduce a tibial tunnel guide over the decorticated base, set guide to 45° to 50°, place a 2-cm vertical incision over an anteromedial tibial guide footprint, advance a 2.4-mm guide pin through the guide, and overream to 5 mm. (6) Passing of the sutures with use of a looped suture passer introduced retrograde through the tibial tunnel to retrieve sutures. (7) Anchor placement and fixation. Apply maximum suture traction, drill a second aperture 0.5 to 1.0 cm distal to the original aperture on the anteromedial aspect of the tibia, pass the suture ends through the anchor, and fix the anchor into the aperture. (8) Repair evaluation and closure. Note the position and stability of the meniscal root relative to the native footprint. Standard closure in layers is performed. Alternatives: If the patient experiences no relief from nonoperative treatment, an MMPRT can be treated operatively via partial meniscectomy or repaired via direct suture-anchor repair or indirect transosseous (transtibial) repair. Direct repair utilizes a suture anchor inserted at the root site5. Variations of the present technique include different suture configurations or numbers of tunnels. Although several suture configurations have been described, the simple cinch stitch (utilized in the present procedure) has been shown to be better at resisting displacement than the locking loop stitch6. Moreover, it has been suggested that simple stitches are less technically difficult and more able to resist displacement because they require less tissue penetration than other stitches7. Lastly, procedures that utilize a single versus a second transtibial tunnel have been shown to be equivalent in cadaveric studies8. Rationale: The desired results of MMPRT repair include anatomic reduction, preservation of meniscal tissue and knee biomechanics, and preservation of hoop stress, which improve activity, function, and symptoms and mitigate degenerative changes and the risk of progression to total knee arthroplasty. Expected Outcomes: At a minimum of 2 years after transosseous repair, the Lysholm, Western Ontario and McMaster Universities Osteoarthritis Index, 12-Item Short Form, and Tegner activity scale were significantly improved8,9. Previous studies have shown significant improvement in the Hospital for Special Surgery and Lysholm scores without radiographic osteoarthritis progression at the same minimum follow-up10. Lastly, in the longest-term follow-up study to date, transosseous repair survivorship was reported to be 99% at 5 years and 92% at 8 years, with failure defined as conversion to total knee arthroplasty11. Important Tips: Pearls○ Decorticate the native meniscal root down to bleeding bone.○ Consider fenestration or percutaneous release of the medial collateral ligament in order to further open a tight medial compartment.○ A self-retrieving suture passer allows the use of standard arthroscopy portals.○ A multiuse variable-angle tibial tunnel drill guide allows point-to-point placement over the native meniscal root insertion.○ A guide with a tip may be easier and more accurate to control.○ Consider different guides when drilling the tibial tunnel, according to the anatomy of the patient.○ A low-profile guide may provide better clearance along the condyles.○ Utilize a cannula when shuttling sutures through the tibial tunnel in order to prevent a soft-tissue bridge.○ With anchor fixation, consider drilling over a guide pin and tapping when the bone is hard.○ Study preoperative imaging to evaluate the amount of arthritis present. Evaluate all compartments on magnetic resonance imaging for additional pathology.Pitfalls○ Obliquity of the tibial tunnel can cause the guide pin and reamer to enter too anteriorly.○ Patient failure to adhere to postoperative rehabilitation and restrictions can lead to unfavorable outcomes.○ The use of lower-strength sutures may increase the risk of fixation failure.

The role of radiation therapy and margin width in localized soft-tissue sarcoma: Analysis from the US Sarcoma Collaborative.

BACKGROUND AND OBJECTIVES: Soft-tissue sarcomas (STSs) are often treated with resection and radiation (RT)±chemotherapy. The role of RT in decreasing resection width to achieve local control is unclear. We evaluated RT on margin width to achieve local control and local recurrence (LR). METHODS: From 2000 to 2016, 514 patients with localized STS were identified from the US Sarcoma Collaborative database. Patients were stratified by a margin and local control was compared amongst treatment groups. RESULTS: LR was 9% with positive, 4.2% with ≤1 mm, and 9.3% with >1 mm margins (P = .315). In the ≤1 mm group, LR was 5.7% without RT, 0% with preoperative RT, and 0% with postoperative RT (P < .0001). In the >1 mm group, LR was 10.2%, 0%, and 3.7% in the no preoperative and postoperative RT groups, respectively (P = .005). RT did not influence LR in patients with positive margins. In stage I-III and II-III patients, local recurrence-free survival was higher following RT (P = .008 and P = .05, respectively). CONCLUSIONS: RT may play a larger role in minimizing LR than margin status. In patients with positive margins, RT may decrease LR to similar rates as a negative margin without RT and may be considered to decrease the risk of LR with anticipated close/positive margins.

Pathologic necrosis following neoadjuvant radiotherapy or chemoradiotherapy is prognostic of poor survival in soft tissue sarcoma.

PURPOSE: Neoadjuvant radiotherapy ± chemotherapy and wide local excision is an accepted management of localized soft tissue sarcomas (STS). Necrosis is prognostic for survival in osteosarcomas, but the significance for STS is undetermined. This study aimed to determine if percent true necrosis, opposed to a combination of necrosis and fibrosis, leads to improved survival in extremity and trunk STS. METHODS: From 2000 to 2015, 162 patients with STS were treated with neoadjuvant therapy and resection. Patient and tumor variables were reviewed, and resected specimens underwent pathological assessment. Necrosis was ratiometrically determined. Overall (OS), distant metastasis-free (DMFS), and progression-free survival (PFS) were calculated using Kaplan-Meier estimator. Survival was determined using the Fisher's exact test for univariate analysis (UVA) and logistic regression for multivariate analysis (MVA). RESULTS: Median follow-up was 4.5 years and median necrosis was 24.97%. Necrosis predicted worse OS, DMFS, and PFS on UVA, and DMFS and PFS on MVA. Necrosis was positively correlated with size and grade. To mitigate the role of size, a sub-analysis of ≥ 10 cm tumors was performed revealing necrosis predicted decreased DMFS and PFS on UVA and MVA. In high-grade tumors, necrosis correlated with decreased DMFS and PFS on UVA. Necrosis did not predict OS in ≥ 10 cm or high-grade tumors. CONCLUSIONS: Our data suggests necrosis may be an additional independent, prognostic variable with increased necrosis predicting a worse prognosis. Necrosis may not be a measure of treatment response and instead suggests more aggressive tumor biology as high-grade, large STS were associated with increased necrosis.

Smoking is predictive of poorer distant metastasis-free and progression free-survival in soft tissue sarcoma patients treated with pre-operative radiotherapy or chemoradiotherapy.

BACKGROUND: Soft tissue sarcomas (STS) are often treated with pre-operative radiation (RT), with or without chemotherapy, followed by wide local excision. Prognosis for these patients involves an interplay of tumor and patient characteristics. Known prognostic determinants include tumor size, grade, response to therapy, and patient characteristics such as age. While smoking is negatively correlated with outcomes in various malignancies, the impact on STS is unknown. We aimed to assess if smoking impacts overall (OS), distant metastasis-free (DMFS), and progression-free (PFS) survival in patients with STS treated with pre-operative RT. METHODS: Between 2000 and 2015, 166 patients with STS were identified from our prospective database. Patient variables were retrospectively reviewed. Smoking was defined as a ≥ 10 pack year history of current and former smokers. Survival was evaluated using the fisher exact test for univariate (UVA) and logistic regression for multivariate (MVA) analysis. RESULTS: Fifty-seven (34.3%) patients had smoking histories of ≥ 10 pack years. On UVA, smoking was associated with decreased DMFS (p = 0.0009) and PFS (p = 0.0036), but not OS (p = 0.05). Smoking held significance on MVA for both DMFS and PFS. Current smokers and patients with ≥ 24-month follow-up demonstrated decreased DMFS and PFS on UVA and MVA. CONCLUSIONS: Current smokers and patients with a significant smoking history demonstrated decreased DMFS and PFS in STS patients treated with pre-operative RT. Smoking may cause immunologic compromise and therefore lead to higher rates of progression and distant metastasis.

Metabolic effects of physiological levels of caffeine in myotubes

Caffeine has been shown to stimulate multiple major regulators of cell energetics including AMP-activated protein kinase (AMPK) and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Additionally, caffeine induces peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alfa) and mitochondrial biogenesis. While caffeine enhances oxidative metabolism, experimental concentrations often exceed physiologically attainable concentrations through diet. This work measured the effects of low-level caffeine on cellular metabolism and gene expression in myotubes, as well as the dependence of caffeine's effects on the nuclear receptor peroxisome proliferator-activated receptor beta/delta (PPAR Beta/Delta). C2C12 myotubes were treated with various doses of caffeine for up to 24 h. Gene and protein expression were measured via qRT-PCR and Western blot, respectively. Cellular metabolism was determined via oxygen consumption and extracellular acidification rate. Caffeine significantly induced regulators of mitochondrial biogenesis and oxidative metabolism. Mitochondrial staining was suppressed in PPARBeta/Delta -inhibited cells which was rescued by concurrent caffeine treatment. Caffeine-treated cells also displayed elevated peak oxidative metabolism which was partially abolished following PPARβ/δ inhibition. Similar to past observations, glucose uptake and GLUT4 content were elevated in caffeine-treated cells, however, glycolytic metabolism was unaltered following caffeine treatment. Physiological levels of caffeine appear to enhance cell metabolism through mechanisms partially dependent on PPARBeta/Delta