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In the intricate landscape of multiple myeloma, a hematologic malignancy of plasma cells, bone disease presents a pivotal and often debilitating complication. The emergence of Chimeric Antigen Receptor T-cell (CAR-T) therapy has marked a pivotal shift in the therapeutic landscape, offering novel avenues for the management of MM, particularly for those with relapsed or refractory disease. This innovative treatment modality not only targets malignant cells with precision but also influences the bone microenvironment, presenting both challenges and opportunities in patient care. In this comprehensive review, we aim to examine the multifaceted aspects of bone disease in patients with multiple myeloma and concurrent CAR-T therapy, highlighting its clinical ramifications and the latest advancements in diagnostic modalities and therapeutic interventions. The article aims to synthesize current understanding of the interplay between myeloma cells, CAR-T cells, and the bone microenvironment in the context of current treatment strategies in this challenging and unique patient population., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Soft-tissue sarcomas present as a mass with nonspecific symptoms, and unplanned excisions commonly occur. The purpose of this study was to analyze the incidence of unplanned excisions performed by orthopaedic surgeons and to conduct a root cause analysis (RCA) of the steps that led to unplanned excisions in all the cases., Methods: A retrospective case-control study was conducted. Two cohorts were identified, one including patients who underwent an unplanned excision of a soft-tissue sarcoma (n = 107) and a second cohort with patients whose entire care was performed at our sarcoma center (n = 102). A RCA was conducted with the whole sample to identify the preventable causes that led to sarcoma unplanned excisions., Results: Orthopedic surgeons were the second group of physicians to perform the most unplanned excisions, only behind general surgeons. Inadequate imaging was encountered in 76.6% of the patients (n = 82, 95% confidence interval, 67.8 to 83.6). Forty-five patients (42.1%) had no imaging studies before the unplanned procedure. In the RCA, the most notable obstacles found were (1) incorrect assumption of a benign diagnosis, (2) failure to obtain the appropriate imaging study, (3) incorrectly reported imaging studies, (4) failure to order a biopsy, and (5) incorrect reporting of the biopsy., Conclusions: Despite educational efforts, unplanned excisions and the devastating consequences that sometimes follow continue to occur. Orthopaedic surgeons persist in playing a role in the unplanned procedure burden., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Purpose of Review: This review summarizes current findings regarding limb amputation within the context of cancer, especially in osteosarcomas and other bony malignancies. We seek to answer the question of how amputation is utilized in the contemporary management of cancer as well as explore current advances in limb-sparing techniques., Recent Findings: The latest research on amputation has been sparse given its extensive history and application. However, new research has shown that rotationplasty, osseointegration, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) can provide patients with better functional outcomes than traditional amputation. While limb-sparing surgeries are the mainstay for managing musculoskeletal malignancies, limb amputation is useful as a palliative technique or as a primary treatment modality for more complex cancers. Currently, rotationplasty and osseointegration have been valuable limb-sparing techniques with osseointegration continuing to develop in recent years. TMR and RPNI have also been of interest in the modern management of patients requiring full or partial amputations, allowing for better control over myoelectric prostheses., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Case: Two cases of revision total hip arthroplasty (THA) for pseudotumor and infection with persistent postoperative bleeding because of angiosarcoma are presented. After surgery, both patients' health deteriorated because of hypovolemic shock despite transfusion, pressors, embolization, and prothrombotics. Diagnosis was obscure and delayed despite extensive imaging. Standard and computed tomography angiogram were nondiagnostic and did not localize the tumors or bleeding. Repeat surgeries and biopsies requiring special staining ultimately revealed epithelioid angiosarcoma., Conclusion: A diagnosis of angiosarcoma was etiologic for persistent postoperative bleeding after revision THA and should be considered in such cases., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C75)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Introduction: The purpose of this historical review is to highlight the progression and development of prosthetic reconstruction with a focus on the modular distal femur with hinged total knee arthroplasty., Method: Scientific literature was searched for descriptions of endoprosthetic reconstruction of the extremities to provide a thorough overview of the subject, focusing the research on the evolution of limb salvage of the distal femur., Results: After the first works of Gluck and Giordano, with ivory and metal and the pioneer shoulder prosthesis by Pean in the late 1890s, a great advancement was brought by reconstructions performed for injured soldiers of the Great War. By the 1940s, replacement of all the main joints had been attempted, and documented., Discussion: Walldius in the 1950s developed a fully constrained hinge knee, offering for the first time a consistent and replicable method of substituting the joint. In 1953, Shiers' prosthesis allowed for good flexion and extension. Stanmore and GUEPAR group prosthesis in the 1960s were the first to have a different right and left side model. The rotating hinge was developed in 1978 by Walker, with the innovative concept of six degrees of freedom. Between 1979 and 1982, Kotz developed the modular segmental replacement that, added to a fixed hinge knee, permitted the revolutionary creation of the modern distal femur replacement., Conclusion: The study of the materials and mechanical solutions that was brought to the modern distal femur resection prosthesis is a good example of a virtuous multidisciplinary teamwork between orthopaedic surgeons, anatomists, and biomechanical engineers., (© 2023. The Author(s) under exclusive licence to SICOT aisbl.)

(1) Background: Pelvic Chondrosarcomas (CS) have a poor prognosis. The grade is the most important survival predictor; other factors are periacetabular location and Dedifferentiated CS subtype. The aim of the study is to investigate a series of CS of the pelvis, to analyze the prognostic factors that affect outcomes and to demonstrate how the use of intraoperative navigation can reduce the complications without worse outcomes. (2) Methods: Retrospective study on 35 patients (21 M, 14 F), median age at surgery 54 years (IQR 41−65), with pelvic CS, treated with hemipelvectomy under navigation guidance. (3) Results: 30 high-grade CS and 5 low-grade CS; mean follow-up 51.4 months. There was a positive linear correlation between the tumor volume and the presence of local recurrence at follow-up. The mean survival time of patients with larger chondrosarcoma volume was lower, but not significantly so. Lower MSTS score was associated with significantly lower survival time (p < 0.001). (4) Conclusion: in this series overall survival, LR and distant metastasis were comparable with recent literature, while complication rate was lower compared to similar series without the use of navigation. There was a correlation between tumor volume and local recurrence rate but not with the presence of metastasis at follow up.

This is a retrospective study that evaluated surgical versus non-surgical treatment of 100 patients followed for up to six years diagnosed with severe osteoporotic vertebral compression fractures (VCF). Fractures were classified by percent collapse of vertebral body height as "high-degree fractures" (HDF) (>50%) or vertebra plana (VP) (>70%). A total of 310 patients with VCF were reviewed, identifying 110 severe fractures in 100 patients. The HDF group was composed of 47 patients with a total of 50 fractures. The VP group was composed of 53 patients with a total of 60 fractures. Surgical intervention was performed in 59 patients, comprised entirely of percutaneous vertebral cement augmentation procedures, including vertebroplasty, balloon kyphoplasty, or cement with expandable titanium implants. The remaining 41 patients only underwent conservative treatment that is the basis of the comparison study. All procedures were performed as an outpatient under local anesthesia with minimal sedation and there were no procedural complications. The initial or pre-procedural visual analog scale (VAS) score averaged 8.4 in all patients, with surgical patients having the most marked drop in VAS, averaging four points. This efficacy was achieved to a greater degree in surgically treated VP fractures compared to HDF. Non-surgical patients persisted with the most pain in both short- and long-term follow-up. This large series, with follow-up up to six years, demonstrated that the more severe fractures respond well to different percutaneous cement augmentation procedures with reduction of pain without increased complications in a comparison to conservatively treated patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Joyce et al.)

Osteosarcoma is the most common primary bone sarcoma and affects both children and adults. The cornerstone of treatment for patients with localized and oligometastatic disease remains neoadjuvant chemotherapy, surgical resection of all sites of disease, followed by adjuvant chemotherapy. This approach is associated with up to an 80% 5-year survival. However, survival of patients with metastatic disease remains poor, and overall, osteosarcoma remains a challenging disease to treat. Advances in the understanding of molecular drivers of the disease, identification of poor prognostic factors, development of risk-stratified treatment protocols, successful completion of large collaborative trials, and surgical advances have laid the ground work for progress. Advances in computer navigation, implant design, and surgical techniques have allowed surgeons to improve patients' physical functional without sacrificing oncologic outcomes. Future goals include identifying effective risk stratification algorithms which minimize patient toxicity while maximizing oncologic outcomes and continuing to improve the durability, function, and patient acceptance of oncologic reconstructions., (Copyright © 2021 by the American Academy of Orthopaedic Surgeons.)

Background: Breast cancer is the most common cancer and second cause of death in women worldwide. Patients with breast cancer are classified into subgroups based on the presence or absence of hormone receptors and the human epidermal growth factor 2-neu (HER-2) marker, the different molecular profiles come with an associated prognosis and variety of possible treatment options. Patients with triple negative cancer have a worse prognosis, a more aggressive behavior, higher likelihood of spreading, a higher risk of recurrence and a poorer outcome overall. Intramedullary rod fixation has proven to provide a good outcome and function in patients with metastatic breast cancer, but no study has addressed the receptor-status potential outcome differences that may affect disease progression at an orthopaedic surgery site., Questions/purposes: (1) Do patients with triple negative breast cancer have a higher revision rate of intramedullary rod fixation of bone metastases? (2) Do patients with metastatic triple negative breast cancer have a higher revision rate of intramedullary rod fixation due to local disease progression?, Methods: This was a single-center, observational, retrospective cohort study. Fifty-seven patients with a diagnosis of breast cancer metastatic to long bones who underwent surgical fixation with an intramedullary rod for a pathological fracture or an impending fracture due to a bone metastasis with a Mirels' score equal or above 8 between January 2004 and December 2016 at our institution were included. All implants used were from the same manufacturer (Stryker Corp., Mahwah, NJ, USA). Patients were divided into two groups based on the receptor status of the tumor and were classified either as triple negative, when the tumor lacked progesterone, estrogen and HER-2 receptors, or as receptor-positive when the presence of one or a combination of either three was proven. In the triple-negative tumor group the mean follow up time was 26 months (SD 29) and median follow up time was 16 months. In the receptor-positive tumor group mean follow up was 27 months (SD 24) with a median follow up of 19 months. To assess possible associations between different factors and the outcomes of interest, we used either the chi-square test or Fisher's exact test for categorical variables and the ANOVA test for continuous variables. For the survival assessment, a Kaplan-Meier analysis was performed and for the cumulative incidence a competing risk analysis was utilized., Results: The intramedullary rod revision rate for patients in the triple-negative tumor group was 17%, while for the receptor-positive group it was 12%, this was not statistically different for our sample size. The mean time for revision of the intramedullary rod in the whole sample was 19 months (SD 11, range 6-40). The causes of revision were disease progression (43%), nonunion (29%) and surgeon error (29%). The cumulative incidence of revision surgery was 6% (CI 95%, 2-14%) at 12 months and 20% (CI 95%, 8-36%) at 60 months., Conclusions: Intramedullary rodding can be considered for the treatment of long bones metastases in breast cancer patients for an impending or actual pathological fracture. There is no difference in the intramedullary rod revision rate among patients with different receptor-status when comparing triple-negative tumor patients and receptor-positive ones., Level of Evidence: Level III, therapeutic study., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

The surgical treatment of osteoporotic vertebral fractures with greater than 70% collapse, known as "Vertebra Plana (VP)" has been controversial. Originally VP was a considered a contraindication to vertebroplasty or kyphoplasty because of presumed difficulty of entering the collapsed vertebra as well as obtaining significant re-expansion or correct associated sagittal kyphosis. In some cases, multilevel pedicle screw fixation with or without attempts to correct the collapse is still performed to correct the kyphosis or prevent progression. With experience it was clear that the pedicle could be accessed and VP could be treated without added risk of epidural leak of cement or epidural extravasation. Now, with the introduction of newer third-generation intraspinal expansion devices that are larger and need to be placed bilaterally, their use in cases of VP was again an issue since VP cases were excluded from the original multicenter studies used for worldwide approval. This report reviews six cases of VP treated with bilateral SpineJack® implants (Stryker Corp, Kalamazoo, Michigan, USA) demonstrating it is not only feasible to place these larger size implants but achieve significant reconstitution of vertebral height as well as correction of the kyphotic deformity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Joyce et al.)

Tenosynovial giant cell tumors are extremely rare tumors with highly nonspecific symptoms. This benign but aggressive disease has a slow course of progression; however, it can ultimately lead to irreversible damage to a joint. Here we describe a case of a 45-year-old female with a diagnosis of tenosynovial giant cell tumors of the distal tibiofibular joint, the second case described in the literature for such location. Appropriate imaging studies and ultimately histologic studies are necessary for the correct diagnosis. Some locations are particularly unusual for these tumors making a high level of suspicion as well as treatment by an oncology orthopedic surgery specialist at a high-volume center paramount., (© 2021 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Melanocytic schwannoma is a rare nerve tumor characterized by melanin-producing neoplastic Schwann cells. Wide surgical resection is the management of choice for this tumor; however, anatomical location and proximity to nerve roots can make locating this tumor and the surgical resection challenging. Here we describe the case of 49-year-old male with a melanocytic schwannoma in the presacral area adjacent to the second sacral nerve root that was managed by wide resection aided by computer-assisted navigation due to the difficulty in identifying its location intraoperatively. The utilization of computer-assisted navigation improves accuracy and precision through the creation of a virtual continuous tridimensional map, particularly useful when oftentimes tumor margins may seem equivocal and further resection would compromise the patient's functionality. The value of computer-assisted navigation for soft tissue tumor resections in orthopedic oncology is still in its infancy, though, in certain scenarios it may advance the technique for some soft tissue resections., (© 2020 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Soft tissue sarcomas (STS) are rare and heterogeneous tumors making chemotherapy use controversial. Our goal was to identify a subset of patients with primary STS that benefit with the addition of chemotherapy., Methods: A retrospective chart review included intermediate to high-grade localized primary STS of the extremity/trunk, and tumor size > 5 cm. The effect of chemotherapy was evaluated for local control (LC), distant control (DC), progression free survival (PFS), and overall survival (OS)., Results: In this cohort (n = 273), patients were treated with surgery (98%), radiation (81%), and chemotherapy (24.5%). With a median follow-up of 51 months, the entire cohort's 5-year LC, DC, PFS, and OS are 79.1%, 59.9%, 43.8%, and 68.7%, respectively. The addition of chemotherapy did not provide a DC benefit (p = 0.238) for the entire cohort. High-grade disease (n = 210) experienced a 5-year benefit in DC (68% vs. 54.4%, p = 0.04), which was more pronounced with MAI (Mesna, Adriamycin, Ifosfamide) based regimens (74.2%, p = 0.016), and a 5-year PFS (50.8% vs 45%, p = 0.025) and OS benefit (76.2% vs 70%, p = 0.067) vs. no chemotherapy. On multivariate analysis of the high-grade subset, chemotherapy independently predicted for a DC benefit (HR 0.48 95% CI 0.26-89, p = 0.019). The benefit of chemotherapy was more pronounced with MAI, showing a significant benefit in DC (HR 0.333 95% CI 0.145-0.767, p = 0.01) and PFS (HR 0.52 95% CI 0.28-0.99, p = 0.047)., Conclusion: In patients with localized STS > 5 cm, the high-grade subset had a distant control benefit with the addition of chemotherapy, leading to improved progression free survival. This is more pronounced with the use of MAI and should be considered in patients eligible for this regimen., Competing Interests: Competing interestsNot applicable., (© The Author(s) 2020.)

Intraosseous lipomas are rare primary benign bone tumors which present with highly nonspecific radiographic features that may lead to equivocal diagnoses. Advanced imaging studies such as MRI with and without contrast and, in some selected cases, tissue sample analyses are required in the diagnostic pathway. Here we describe the second case in the literature of an intraosseous lipoma of the clavicle and the first with extraosseous extension. Subsequent to histologic confirmation the lesion was monitored with clinical and radiologic evaluation., (© 2020 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Despite an abundance of evidence, routine perioperative antifibrinolytics have been avoided in oncology patients due to concern of thrombosis when given to patients with a preexisting hypercoagulable state. We present a retrospective review of 104 patients with an oncologic diagnosis who received intraoperative tranexamic acid during orthopedic surgery. Overall, complication rates were low, including deep vein thrombosis (1.0%), pulmonary embolism (4.8%), stroke (0%), and myocardial infarction (0%). This preliminary evidence shows that antifibrinolytics such as tranexamic acid may be considered perioperatively in oncology patients without increased risk of thromboembolic events; however, further prospective trials are encouraged.

Atypical hemangiomas of the spine can mimic metastatic lesions on magnetic resonance imaging, therefore making this distinction is a diagnostic challenge. In most cases, this conundrum can usually be solved with positron emission tomography/computed tomography images, because hemangiomas do not usually present with increased uptake while metastatic lesions do. Here we present a case of a patient with a unique diagnosis, myxoid liposarcoma, in which the vertebral metastatic lesion did not present with increased uptake in positron emission tomography/computed tomography scans. While keeping the imaging particularity of this rare sarcoma in mind, proceeding with a biopsy when the suspicion of metastasis remains high will help elucidate the diagnosis and allow for proper management., (© 2019 The Authors.)

Intramuscular myxomas (IM) are rare benign tumors of mesenchymal origin. These tumors have a high myxoid content and a nonspecific radiologic appearance. Here we describe the case of a patient with an IM in an infrequent location; within the obturator externus muscle. A singular approach was utilized for the resection of this tumor in such rare location. Despite IM being benign tumors, patients may require a surgical excision due to the difficulty of differentiating these tumors, with unreliable imaging features, from other myxoid soft tissue masses.

Purpose: Sarcomas are a diverse group of malignant tumors that arise from soft tissues or bone. For most advanced cases, there is a substantial need for improved therapeutic options and, therefore, a desire to more precisely tailor therapy in individual cases. In this study, we review our institutional experience with next-generation sequencing (NGS)-based molecular profiling for non-GI stromal tumors sarcomas, with a focus on the clinical utility of the results., Patients and Methods: We retrospectively analyzed results of NGS performed on tumors from 114 patients with a diagnosis of sarcoma. A chart review was conducted to review the clinical impact of NGS findings., Results: A median of three putatively oncogenic gene alterations were identified per tumor sample (range, 0 to 19) and at least one mutation was detected in 96.7% of tumors. Fifty-six patients (49.1%) harbored a finding that was felt to be actionable after review by a molecular tumor board. Five patients (4.4%) had a diagnosis change as a result of NGS findings. In 15 patients (13.2%), therapeutic selection was influenced by NGS findings. Four of 15 (26.7%) of the NGS-influenced systemic therapies resulted in clinical benefit., Conclusion: Putatively oncogenic mutations are readily detected in the majority of sarcomas. Genetic profiling affected the diagnosis and/or treatment approach in a sizeable minority of patients with sarcoma treated at our center. Additional study is required to determine if genetic profiling leads to improved clinical outcomes.

Parachordoma is a rare entity with less than 50 cases described in the literature. This soft-tissue tumor resembles chordomas as well as extraskeletal myxoid chondrosarcomas and has only recently been fully characterized. Here we describe the case of a patient with a lower back parachordoma and its subsequent postresection recurrence 9 years after the initial procedure, emphasizing the importance of long-term follow-up in individuals with this diagnosis.

Background: RAF family activating fusions have been described as a potentially targetable molecular finding in a subset of soft tissue sarcomas. To further expand upon the landscape of this genetic feature, we describe a novel MTAP-RAF1 activating fusion identified in a S100 positive soft tissue sarcoma., Case Presentation: A 51 year old man underwent excision of a soft tissue mass in his foot. Pathology revealed a spindle cell neoplasm with S100 positivity, ultimately classified as a soft tissue sarcoma, not otherwise specified. Comprehensive molecular profiling was performed to help establish the diagnosis and revealed a novel MTAP-RAF1 fusion that includes the tyrosine kinase domain of RAF1., Conclusions: Our report adds to the spectrum of fusion-driven RAF activation observed in soft tissue sarcomas and lends additional evidence that RAF activation plays an important role in some soft tissue sarcomas. Identification of novel fusions involving the MAPK/ERK pathway in sarcomas may provide new avenues for precision medicine strategies involving targeted kinase inhibitors.

Background: Altered anatomy in a previously irradiated surgical bed can make accurate localization of anatomic landmarks and local recurrence nearly impossible. The use of intraoperative MRI (iMRI) has been described in neurosurgical settings, but to our knowledge, no such description has been made regarding its utility for local recurrence localization in sarcoma surgery., Case Description: A 58-year-old female presented after previously undergoing two previous resection and reresection procedures of a myxoid liposarcoma located adjacent to her proximal femoral vasculature. After postoperative radiation therapy, she was referred to our institution where she underwent two additional reexcisions of local recurrences during a 3-year span, eventually undergoing a regional rotational muscle flap for coverage. Two years after her third reexcision procedure, she presented with two additional, nonpalpable surgical-bed local recurrences. After converting an MRI bed and scanner to allow for proximal thigh imaging in an iMRI surgical suite, the patient underwent a successful resection that achieved negative margins. To date, she remains without evidence of disease at 37 months., Literature Review: Real-time iMRI in neurosurgical studies has shown a high rate of residual disease leading to immediate subsequent reexcision, thus lending to improved rates of negative margin resection. To our knowledge, this is the first example using iMRI technology to remove a recurrent soft tissue sarcoma that otherwise was clinically nonlocalizable., Clinical Relevance: The use of an iMRI surgical suite can aid with identification of soft tissue nodules in conditions such as an altered tumor bed from prior resection and radiotherapy, which otherwise make recurrences difficult to localize. A team approach between administration, surgeons, and engineers is required to design and pragmatically implement the use of an MRI-compatible table extension to enhance existing iMRI surgical suite technology for extremity sarcoma resection procedures.

Background: Total hip arthroplasty (THA) can be associated with substantial peri-operative blood loss which can negatively influence a patient's clinical outcome. Few haemostatic agents have been tested in THA. The aim of this study was to determine whether the use of a collagen/thrombin/ autologous platelet haemostatic agent would result in a significant decrease of blood transfusions for patients undergoing primary THA., Materials and Methods: THA patients meeting inclusion/exclusion criteria (n=109) were enrolled in this prospective, double-blind trial and randomised to a treatment arm (standard haemostatic methods plus haemostatic agent) or control arm (standard haemostatic methods only). The primary outcome was transfusion. Secondary outcome measures included peri-operative narcotic usage and post-operative haemoglobin levels, pain scores, function, and general health quality of life., Results: Transfusions were required by 5/60 (8.3%) patients in the treatment group and 7/49 (14.3%) in the control group (p=0.33). The mean number of units transfused was not significantly different between the treatment group (2.2±1.3) and the control group (1.6±0.5) (p=0.36). Haemoglobin values on post-operative days 1, 2, and 3 were significantly higher in the treatment group (p=0.002, 0.04, and 0.02, respectively). Hip Disability and Osteoarthritis Outcome Score and Short Form-12 scores were not different between the two groups., Discussion: In relatively healthy patients undergoing primary cementless THA there was no significant difference in number of transfusions or number of units transfused. It is unlikely that we will routinely use the investigated haemostatic agent to reduce blood loss in a healthy patient undergoing THA. The product may have some benefit in patients who refuse blood transfusions, have minimal ability to increase blood volume, are undergoing total joint revision, or have markedly low pre-operative haemoglobin levels, but this needs to be demonstrated.

Revision total knee arthroplasty (RTKA) requires preoperative planning to enable the reconstruction of bony deficiencies. The objective of this project was to identify predictors of bone loss management at RTKA based on the preoperative failure mode and patient demographics known preoperatively. We retrospectively reviewed 245 consecutive RTKA procedures in which the same revision knee system was utilized. Patient demographic and treatment data were recorded, and locations of bone loss were identified based on the reconstructive management. We identified significant predictors for use of femoral augments at all four positions. Several predictors significantly predisposed to use of a thick (>19 mm) polyethylene; however, no predictors of tibial augments were significant. Although the reconstruction of bone loss is primarily based on the intraoperative assessment, these findings may provide additional information to help the surgeon prepare for difficult revision procedures.

Background: Combinations of gemfibrozil and a 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase inhibitor show promise in treating mixed lipid abnormalities. However, concern regarding the risk of myopathy and hepatic toxicity has limited the use of this combination. To determine the long-term safety and efficacy of this combination, we prospectively identified all patients placed on a combination of gemfibrozil and any HMG reductase inhibitor., Methods: Pravastatin, simvastatin, fluvastatin, lovastatin, or atorvastatin at incremental doses was combined with gemfibrozil (600 mg twice daily). Lipid profiles, creatine kinase levels, and aminotransferase levels were monitored. Two hundred fifty-two patients with established atherosclerosis receiving combination therapy for a mean of 2.36 +/- 1.52 years spanning a total of 593.6 patient-years were monitored., Results: In 148 patients, gemfibrozil was started before an HMG was added. The pretreatment total cholesterol level fell from 222 +/- 34 mg/dL to 181 +/- 26 mg/dL (P <.001) on combination therapy. HDL cholesterol level rose from 30 +/- 5 mg/dL to 36 +/- 7 mg/dL (P <.01), triglyceride level fell from 361 +/- 141 mg/dL to 212 +/- 101 mg/dL (P <.03). The ratio of total cholesterol to HDL fell from 7.6 +/- 1. 7 to 5.3 +/- 1.6 (P <.001). In 104 patients an HMG was begun before gemfibrozil was added. Pretreatment total cholesterol level fell from 246 +/- 54 mg/dL to 192 +/- 40 mg/dL on combination therapy (P <.01). HDL level rose from 33 +/- 9 mg/dL to 38 +/- 9 mg/dL (P <.03) and triglyceride level fell from 314 +/- 183 mg/dL to 183 +/- 93 mg/dL (P <.001). The ratio of total cholesterol to HDL fell from 7.9 +/- 3.6 to 5.2 +/- 1.4 (P <.001). In both groups the lipid profile on combination therapy was significantly better than that obtained on single-agent therapy. One episode of myopathy (0.4%) and one episode of aminotransferase level elevation (0.4%) of greater than 3 times upper limit of normal occurred. Both resolved with cessation of therapy without consequence., Conclusions: Combinations of gemfibrozil and an HMG, compared with either agent alone, results in improved long-term control of lipid abnormalities in mixed lipid disorders. The low incidence of toxicity permits the use of combination therapy in patients at high risk of atherosclerotic complications.

Normal binocular vision requires that all involved structures; ocular, muscular, and neuronal; be intact and all of the intricate processes controlling conjugate gaze and cortical fusion be functioning. Diplopia may represent pathology at any point in this complex system. A careful history and physical examination may reveal a relatively benign etiology or may compel rapid diagnostic studies to evaluate the patient for neurological catastrophe.

A liquid chromatographic (LC) method has been developed for determination of thiamine in infant formula products. The method involves the following steps: (a) dissolution of the formula with water, (b) pH adjustment to induce protein precipitation, (c) filtration, (d) concentration of thiamine by using a cation exchange column and extraction system, (e) cleanup of adsorbed thiamine and other contaminants on the ion exchange column by washing with water and then methanol, (f) elution of thiamine with a mixture of methanol-2M potassium chloride buffer, (g) analysis for thiamine by liquid chromatography. Thiamine is separated from its phosphate esters, the mono-, di-, and triphosphates, as well as its antagonists oxythiamine and pyrithiamine on a 6 micron particle size column and a mobile phase of 40mM triethyl-ammonium phosphate buffer-methanol (pH 7.7) (90 + 10). The method is reproducible, with relative standard deviations ranging from +/- 0.76 to +/- 1.2%, depending on the infant formula product tested. Recovery of thiamine from various infant formula products is greater than 99%. Analysis for thiamine of several commercially available infant formulas at different levels of fortification gave results that ranged from 122 to 216% of the declared levels. These results agree well with those obtained using the AOAC fluorometric method.