Tranexamic acid improves early postoperative mobilization in cancer patients undergoing endoprosthetic reconstruction.

BACKGROUND AND OBJECTIVES: Tranexamic acid (TXA) has been shown to decrease perioperative blood loss, transfusions, and cost in patients undergoing resection of aggressive bone tumors and endoprosthetic reconstruction. This study explored the effect of TXA administration on postoperative mobilization in these patients. METHODS: This study included 126 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction; 61 patients in the TXA cohort and 65 patients in the non-TXA cohort. Postoperative physical therapy (PT) and occupational therapy notes were reviewed; patient ambulation distance and duration of therapies were recorded. RESULTS: Patients in the TXA cohort ambulated further on all postoperative days, which was significant on postoperative Day 1 (POD1) (p = 0.002) and postoperative Day 2 (POD2) (p < 0.001). The TXA cohort ambulated 85% further per PT session 87.7 versus 47.4 ft (p < 0.001) and participated 14% longer, 36.1 versus 31.7 min (p < 0.001). Multivariate analysis identified a significant inverse association between postoperative hospitalization length and POD1, POD2, postoperative Day 3, and total ambulation (p < 0.001). Blood transfusion was independently associated with a 1.5 day increase in postoperative hospitalization (95% confidence interval: 0.64-2.5; p < 0.001). CONCLUSIONS: TXA administration was associated with increased postoperative ambulation and endurance. Increased postoperative ambulation was associated with decreased length of stay and increased likelihood to discharge home.

Tranexamic Acid in Patients With Cancer Undergoing Endoprosthetic Reconstruction: A Cost Analysis.

INTRODUCTION: Tranexamic acid (TXA) decreases blood loss, perioperative transfusion rates, and cost in total hip and total knee arthroplasty. In a previous study, topical TXA decreased both perioperative blood loss and transfusions in patients undergoing resection of aggressive bone tumors and endoprosthetic reconstruction. The purpose of this study was to explore the cost effectiveness of TXA in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction, assessing transfusion cost, TXA administration cost, postoperative hospitalization cost, posthospital disposition, and 30-day readmissions. METHODS: This study included 126 patients who underwent resection of an aggressive bone tumor and endoprosthetic resection at a single academic medical center; 61 patients in the TXA cohort and 65 patients in the non-TXA cohort. The cost of 1 unit of packed red blood cells, not including administration or complications, was estimated at our institution. The cost of hospitalization was estimated for lodging and basic care. The cost of TXA was $55 per patient. Patients were followed up for 30 days to identify hospital readmissions. RESULTS: Patients in the TXA cohort experienced a TXA and blood transfusion cost reduction of $155.88 per patient (P = 0.007). Proximal femur replacement patients experienced a $282.05 transfusion cost reduction (P = 0.008), whereas distal femur replacement patients only experienced a transfusion cost reduction of $32.64 (P = 0.43). An average hospital admission cost reduction of $5,072.23 per patient (P < 0.001) was associated with TXA use. Proximal femur replacement patients who received TXA experienced a hospital cost reduction of $5,728.38 (P < 0.001), whereas distal femur replacement patients experienced a reduction of $3,724.90 (P = 0.01). No differences between the cohorts were identified in discharge to home (P = 0.37) or readmissions (P = 0.77). DISCUSSION: TXA administration is cost effective in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction through reducing both perioperative transfusion rates and postoperative hospitalization. LEVEL OF EVIDENCE: III-Retrospective Cohort Study.

Reconstruction with Total Scapular Reverse Total Shoulder Endoprosthesis after Radical Tumor Excision.

Malignant musculoskeletal tumors about the shoulder girdle region involving the scapula are fairly rare, but when diagnosed, challenging and complex surgical treatment may be warranted with the primary goal of improving patient survival. These tumors are typically extensive and infiltrative at the time of presentation, requiring radical resection to achieve margins and obtain local tumor control. Historically, forequarter amputation or flail extremity were the mainstays of treatment in these cases. Presently, with recent advances in diagnostics, imaging, adjuvant therapies, and surgical treatment, many patients presenting with malignant tumors involving the scapula are candidates for limb salvage surgery. Reconstruction with endoprosthesis seems to have gained acceptance as the preferred surgical treatment for such lesions, as this intervention has resulted in improved postoperative function and cosmesis, with an acceptable complication rate. We present our experience with recent advancement in these surgical efforts in the form of shoulder girdle reconstruction with total scapular reverse total shoulder prosthesis after radical tumor excision.

The Ever-Changing World of Limb Salvage Surgery for Malignant Bone Tumors.

The treatment of malignant bone tumors, also called bone sarcomas, has changed dramatically over the past 50 years owing to the advances in chemotherapy, immunotherapy, targeted therapy, radiation, prosthetic technology, and surgical advances. There are 3 main primary bone cancers: osteosarcoma, Ewing's sarcoma (or Ewing's family of sarcoma), and chondrosarcoma. Before advances in limb preservation techniques and before the development of prosthetic replacement, the treatment for a malignant bone tumor of the extremity was amputation. This article discusses the progression of surgical treatment of malignant bone cancers.

Ideological Sorting of Physicians in Both Geography and the Workplace.

CONTEXT: The distribution of physicians across geography and employers has important implications for the delivery of medical services. This study examines how the political beliefs of physicians influence their decisions about where to live and work. METHODS: Physician relocation and employment patterns are analyzed with a panel constructed from the National Provider Identifier directory. Data on political donations are used to measure the political preferences of physicians. FINDINGS: The "ideological fit" between a physician and his or her community is a key predictor of both relocation and employment decisions. A Democratic physician in a predominantly Republican area is twice as likely to relocate as a Republican counterpart living there; the reverse is also true for Republicans living in Democratic areas. Physicians who do not share the political orientation of their colleagues are more likely to change workplaces within the same geographic area. CONCLUSIONS: Physicians are actively sorting along political lines. Younger physicians have trended sharply to the left and are increasingly drawn to urban areas with physician surpluses and away from rural areas suffering from physician shortages. The findings also help explain why physician shortages are more prevalent among left-leaning specialties such as psychiatry.

Tranexamic Acid in Patients With Cancer Undergoing Endoprosthetic Reconstruction: A Retrospective Review.

INTRODUCTION: Endoprosthetic reconstruction presents a significant risk of perioperative blood loss. Tranexamic acid (TXA) is an antifibrinolytic agent used to reduce blood loss in orthopaedic procedures. The safety and efficacy of TXA in arthroplasty are well documented. There is, however, a dearth of literature exploring the safety and efficacy of TXA in musculoskeletal oncology patients. This retrospective, comparative study explores the effects of TXA on perioperative blood loss, blood transfusion rates, venous thromboembolism (VTE) occurrence, and hospital stay in patients undergoing resection of an aggressive bone tumor and endoprosthetic reconstruction. METHODS: For the study, charts from a total of 90 patients who underwent resection of an aggressive bone tumor and endoprosthetic reconstruction were reviewed; of these patients, 34 were in the TXA group and 56 in the non-TXA group. Study participants composed of a heterogeneous group of patients with primary bone sarcoma and metastatic osseous disease. Patients in the TXA group received 1 g of topical TXA administered into the wound bed before closure. The Hemoglobin Balance method was used to calculate blood loss. Patients were followed for 6 weeks. RESULTS: Patients undergoing proximal femur replacement and distal femur replacement in the TXA group experienced a 796 and 687 mL reduction in 72-hour mean blood loss, respectively (P = 0.0003 and P = 0.006). Average blood transfusions decreased by 0.45 U of packed red blood cells per patient in the TXA group (P = 0.048) and transfusion incidence decreased by 21.1% compared with the non-TXA group (P = 0.04). Patients undergoing proximal femur replacement in the TXA group left the hospital 2.2 days earlier than those in the non-TXA group (P = 0.0004). No increase in VTE rate was observed with TXA use. DISCUSSION: This study found results similar to total joint arthroplasty with regard to TXA's effect on perioperative blood loss, transfusion rates, hospital stay, and VTE occurrence. It provides initial data to support the efficacy of topical TXA use in this patient cohort. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

Ipsilateral rotational double-barrel fibula autograft for limb salvage in a pediatric patient with lower extremity intramedullary osteosarcoma: A case report.

Osteosarcoma is a relatively uncommon diagnosis that often requires limb salvage techniques in young patients. Due to the potential long-life expectancy of these patients, techniques which avoid prostheses are preferred to limit the need for future revision surgeries. This case report presents a 9-year-old male diagnosed with intramedullary well-differentiated osteosarcoma of the tibial diaphysis. This limb salvage procedure utilized a rotational ipsilateral vascularized double barrel fibula autograft measuring a total of 24.5 cm when harvested but osteotomized to lengths of 11 and 12.5 cm limbs to reconstruct an 11 cm tibial shaft defect. Anterior chamfer cuts were performed on one limb allowing it to be inserted intramedullary while the second limb was then placed with an inlay technique posterolaterally and then compressed with a carbon fiber plate. The patient recovered well initially postoperatively but was taken back for revision of the carbon fiber plate 10 weeks postoperatively secondary to asymptomatic loosening of the proximal screws. The patient subsequently healed and experienced full graft incorporation with expected hypertrophy of the graft. At most recent follow-up at 19 months, the patient reported no pain and was utilizing the extremity in a normal fashion with no activity limitations. In this report, we present a case of the use of an ipsilateral rotational double-barrel fibula autograft for limb salvage in a pediatric patient with lower extremity intramedullary osteosarcoma.

Physician activism in American politics: The opposition to the Price nomination.

Although a substantial literature considers physician advocacy fundamental to medical professionalism, only a minority of physicians actually pursue it. We analyze the characteristics of 6,402 physicians who engaged in political advocacy by signing the Clinician Action Network's 2016 petition objecting to the American Medical Association's endorsement of the nomination of Tom Price as Secretary of Health and Human Services. These physicians were matched to the NPI (all physicians) and PECOS (largely Medicare payment recipients) directories. Physicians in the directories were matched to publicly disclosed campaign contributions. Contributions are used to measure political preferences expressed on a liberal-conservative scale. We document a pronounced generational realignment in the politics of the medical profession, with recent graduates trending sharply Democratic. Petition signing vs. non-signing is responsive to gender, specialty, geographic location, personal liberal-conservative preferences and year of graduation from medical school. Petition signers were more likely to be women (62% of signers versus 34% of non-signers), recent medical school graduates (58% of signers versus 42% of non-signers), and in lower-paying specialties (27% of signers versus 12% of non-signers). The changing face of physician advocacy has important implications for understanding how the medical profession is likely to influence health care policy in coming decades.

Physicians' political preferences and the delivery of end of life care in the United States: retrospective observational study.

OBJECTIVES: To compare the delivery of end of life care given to US Medicare beneficiaries in hospital by internal medicine physicians with Republican versus Democrat political affiliations. DESIGN: Retrospective observational study. SETTING: US Medicare. PARTICIPANTS: Random sample of Medicare beneficiaries, who were admitted to hospital in 2008-12 with a general medical condition, and died in hospital or shortly thereafter. MAIN OUTCOME MEASURES: Total inpatient spending, intensive care unit use, and intensive end of life treatments (eg, mechanical ventilation and gastrostomy tube insertion) among patients dying in hospital, and hospice referral among patients discharged but at high predicted risk of 30 day mortality after discharge. Physicians were categorized as Democrat, Republican, or non-donors, using federal political contribution data. RESULTS: Among 1 480 808 patients, 93 976 (6.3%) were treated by 1523 Democratic physicians, 58 876 (4.0%) by 768 Republican physicians, and 1 327 956 (89.6%) by 23 627 non-donor physicians. Patient demographics and clinical characteristics were similar between groups. Democrat physicians were younger, more likely to be female, and more likely to have graduated from a top 20 US medical school than Republican physicians. Mean end of life spending, after adjustment for patient covariates and hospital specific fixed effects, was US$17 938 (£12 872; €14 612) among Democrat physicians (95% confidence interval $17 176 to $18 700) and $18 409 among Republican physicians ($17 362 to $19 456; adjusted Republican v Democrat difference, $472 (-$803 to $1747), P=0.47). Intensive end of life treatments for patients who died in hospital did not vary by physician political affiliation. The proportion of patients discharged from hospital to hospice did not vary with physician political affiliation. Among patients in the top 5% of predicted risk of death 30 days after hospital discharge, adjusted proportions of patients discharged to hospice were 15.8%, 15.0%, and 15.2% among Democrat, Republican, and non-donor physicians, respectively (adjusted difference in proportion between Republicans v Democrats, -0.8% (-2.7% to 0.9%), P=0.43). CONCLUSIONS: This study provided no evidence that physician political affiliation is associated with the intensity of end of life care received by patients in hospital. Other treatments for politically polarised healthcare issues should be investigated.

In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.

The long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease.

Use of a Resin-Bonded Bridge to Replace a Congenitally Missing Lateral Incisor: Treatment of "Intrusion" of Teeth.

Craniofacial growth is an important factor to consider when providing dental implant treatment for adolescents to replace missing teeth. Ongoing longitudinal observation has demonstrated that such tooth replacements may appear intruded over time, because there may be ongoing downward and anterior movement of both the alveolus and the teeth at a rate exceeding that of the dental implant, which acts like an ankylosed unit. This case reports on a 23.5-year-old female patient who, at age 16, had orthodontics completed and was left with a space where the maxillary right lateral incisor was congenitally missing with the hope of future restoration with a dental implant. A resin-bonded bridge had been placed to fill the space in the interim. After approximately 7.5 years, the bridge loosened and the patient sought an implant option as its replacement. Clinical images revealed that the bridge, which contained two bonded wings, may have limited physiologic growth, causing both the maxillary right central incisor and canine to appear intruded compared with the left central incisor and canine. This case illustrates, at the very least, that growth and development may not be complete in females aged 16 years and that the way in which a missing tooth is replaced must be carefully considered given the impact that ongoing growth and development may have on restorative care. Moreover, further growth and development may also impact adults.

Bilateral deltoid myositis ossificans in a weightlifter using anabolic steroids.

A 40-year-old male weightlifter presented with a 6-month history of a painless mass in the right deltoid. He had no history of trauma to the shoulder other than an arthroscopic rotator cuff repair a few weeks earlier. Physical examination showed a firm, nontender mass located longitudinally and coinciding with the deltoid, measuring 12×14×4 cm. There was no limitation in range of motion or functioning. Magnetic resonance imaging (MRI) and computed tomography (CT) scans suggested a lobulated, heterogeneous mass with multiple areas of calcification that raised suspicion for soft tissue sarcoma vs myositis ossificans. Marginal resection of the soft tissue mass was performed, and pathologic studies confirmed the diagnosis of xanthogranulomatous myositis ossificans with dystrophic calcifications and central cystic degeneration. At 2-week follow-up, the patient had improved range of motion and pain, but he noted a second soft tissue mass in the left deltoid. The MRI and CT scans showed a 10.5×16×3.4-cm linear, lobulated lesion with multiple calcifications, similar in appearance to the contralateral deltoid. The patient admitted to frequently injecting anabolic steroids into his deltoids. Because the patient was asymptomatic on the left side and the MRI appearance of the left deltoid mass was similar to that of the myositis ossificans seen on the right side, the patient opted for nonsurgical treatment. This is a rare case of myositis ossificans occurring bilaterally in the deltoids after repeated injections of anabolic steroids. There is currently no known association between anabolic steroids and myositis ossificans. This condition often mimics malignant neoplasms, illustrating the necessity of resection for diagnostic confirmation.

The political polarization of physicians in the United States: an analysis of campaign contributions to federal elections, 1991 through 2012.

IMPORTANCE: Few current data are available regarding the political behavior of American physicians as the number of female physicians has increased and the number of solo practitioners has decreased. OBJECTIVE: To analyze campaign contributions that physicians made from the 1991 to 1992 through the 2011 to 2012 election cycles to Republican and Democratic candidates in presidential and congressional races and to partisan organizations, including party committees and super political action committees (Super PACs). DESIGN, SETTING, AND PARTICIPANTS: We explored partisan differences in physician contributions by sex, for-profit vs nonprofit practice setting, and specialty using multiple regression analysis. We studied the relation between the variation in the mean annual income across specialties and the mean percentage of physicians within each specialty contributing to Republicans. MAIN OUTCOMES AND MEASURES: Differences in contributions to Republicans and Democrats, for all physicians and for subgroups. RESULTS: Between the 1991 to 1992 and the 2011 to 2012 election cycles, physician campaign contributions increased from $20 million to $189 million, and the percentage of active physicians contributing increased from 2.6% to 9.4%. Of physicians who contributed during the study period, the mean percentage contributing to Republicans was 57% for men and 31% for women. Since 1996, the percentage of physicians contributing to Republicans has decreased, to less than 50% in the 2007 to 2008 election cycle and again in the 2011 to 2012 election cycle. Contributions to Republicans in 2011 to 2012 were more prevalent among men vs women (52.3% vs 23.6%), physicians practicing in for-profit vs nonprofit organizations (53.2% vs 25.6%), and surgeons vs pediatricians (70.2% vs 22.1%). In 1991 to 1992, these contribution gaps were smaller: for sex, 54.5% vs 30.9%; for organizations, 54.2% vs 40.0%; and for specialty, 65.5% vs 32.7%. The percentage of physicians contributing to Republicans across specialties correlated 0.84 with the mean log earnings of each specialty; specialties with higher mean earnings had higher percentages of physicians contributing to Republicans. CONCLUSIONS AND RELEVANCE: Between 1991 and 2012, the political alignment of US physicians shifted from predominantly Republican toward the Democrats. The variables driving this change, including the increasing percentage of female physicians and the decreasing percentage of physicians in solo and small practices, are likely to drive further changes.

Atypical intradermal smooth muscle neoplasms (formerly cutaneous leiomyosarcomas): case series, immunohistochemical profile and review of the literature.

Atypical intradermal smooth muscle neoplasms (AISMN, formerly known as cutaneous leiomyosarcomas) are uncommon neoplasms, which seem to be remarkable for their excellent prognosis in contrast to their deeper counterparts. The rarity of AISMN has posed a challenge for characterizing the morphologic spectrum, immunohistochemical staining pattern, and behavior. In this study we evaluated the histologic and immunohistochemical features of 20 cases of AISMN. Clinical follow-up was available on 19 out of 20 patients and ranged from 1 to 124 months with an average of 35 months and a median of 20 months with a male predominance (male to female ratio was 2.3:1). Our data show a wide variation in differentiation and atypical features. Among these, the presence of mitotic figures is diagnostically valuable in rendering the final diagnosis. A broad panel of immunohistochemical stains revealed that smooth muscle actin and muscle specific actin, when used in combination, identified smooth muscle differentiation in 100% of the cases. With some caveats, CD34, S100, and CK 5/6 were helpful in ruling out other important cutaneous spindle cell neoplasms. Significantly, loss of phosphatase and tensin homolog (PTEN) staining was seen in the majority of our cases (80%), supporting a role for PTEN loss in the etiology of these lesions. Logistic regression analysis revealed that positive margin status was helpful for predicting recurrence (100% sensitivity and 94% specificity). We conclude that AISMN can have significant morphologic variation and overlap with other spindle cell neoplasms of the skin and that a limited panel of key immunohistochemical stains should be used to distinguish this lesion. The different surgical measures such as wide excision versus Mohs procedure showed a similar clinical outcome. Although the significance of frequent PTEN loss supports a molecular mechanism of tumor genesis, the diagnostic utility of the stain remains to be determined.

Expression of Vascular Endothelial Growth Factor correlates with the advance of clinical osteosarcoma.

PURPOSE: Osteosarcoma is the most common primary malignancy in orthopaedic surgery. Studies suggest that expression of VEGF and high vascularity within osteosarcoma may correlate with poor prognosis. The purpose of this study was to determine whether there was a correlation of VEGF expression with clinical tumour stage and metastasis. METHODS: This retrospective case series examined 54 cases of osteosarcoma patients who were treated during a ten-year period. Relevant clinical information included age, gender, tumour location, stage, adjuvant therapy, morbidity, mortality, and tumour subtypes. The clinical information was analysed for correlation of VEGF expression and tumour prognosis. Tumour sections were examined by routine H&E and by immunohistochemistry for VEGF, CD31, and the oncogenes c-myc and c-fos. RESULTS: There was a significantly positive correlation between VEGF expression and tumour stages among these cases (p < 0.01). The data also suggested a higher cancer recurrence and more frequent cases of remote metastasis in the high-VEGF group compared to the low-VEGF group. VEGF expression also positively associated with c-fos and c-myc expressions in the primary tumour sections. CONCLUSION: The results of this study highlight the role of VEGF in angiogenesis and tumour burden. Data also suggest the influence of VEGF may associate with the elevations of c-fos and c-myc expression. The development of novel therapies to target the VEGF pathway in osteosarcoma may lead to improved survival.

Aggressive squamous cell carcinoma originating as a Marjolin's ulcer.

BACKGROUND: Marjolin's ulcer is an epidermoid carcinoma arising in a scar or chronic wound and can have an aggressive course. OBJECTIVE: To present a case of squamous cell carcinoma arising in a burn scar with resulting metastases and to discuss Marjolin's ulcer. RESULTS: The patient continued to have further metastatic disease despite aggressive surgical treatment. CONCLUSION: In following patients with chronic ulcers and wounds, it is important to evaluate any changes immediately with biopsies and further imaging studies if indicated in order to treat effectively. Even aggressive surgical intervention will sometimes be inadequate in treating these tumors.

Skeletal muscle metastases at sites of documented trauma.

OBJECTIVE: Hematogenous metastases to skeletal muscles have been reported to be rare. We report eight biopsy-proven cases of skeletal metastases occurring in sites of previously documented skeletal muscle trauma. We retrospectively reviewed MR imaging examinations obtained at a large orthopedic surgical oncology service from January 1994 through December 2000 for biopsy-proven metastases to skeletal muscles. Our retrospective review revealed 28 patients with biopsy-proven skeletal muscle metastases. Of these 28 patients, eight had a documented clinical history of previous trauma at the site of skeletal metastasis. Five of these eight patients underwent MR imaging before the development of a metastasis. MR imaging revealed a hematoma in three of the five patients and a partial muscle tear in two of the five patients. The hematomas and partial muscle tears were in the same skeletal muscle location in which the metastatic disease subsequently developed. Metastatic disease was documented by MR imaging and subsequent biopsy. CONCLUSION: Skeletal muscle injury may alter muscle physiology and result in increased susceptibility to the development of metastatic disease at such sites.