Postoperative Computed Tomography Scans of Acetabular Fractures Routinely Identify Indications for Revision Surgery.

OBJECTIVES: To investigate the utility of postoperative computed tomography (CT) scans in identifying indications for revision surgery after surgical fixation of acetabular fractures. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENT SELECTION CRITERIA: Patients with surgically treated acetabular fractures with surgical fixation (open reduction and internal fixation or percutaneous fixation) with routine postoperative CT scans. OUTCOME MEASURES AND COMPARISONS: Primary outcome-revision surgery based on postoperative imaging, including intra-articular osteochondral fragments, implant complications, and malreductions. Secondary outcome-quality of reduction on radiographs versus CT scans. RESULTS: One hundred forty-eight patients were included. The revision surgery rate was 15.5% (23/148); indications included malpositioned implants (6.7%, n = 10), malreductions (5.4%, n = 8), and intra-articular loose bodies (3.4%, n = 5). Only 8.7% (2/23) of the indications for revision surgery were identified on postoperative radiographs, with the remainder being identified on CT scans. Revision surgeries were found to be associated with male gender (proportional difference: 19.6%, 95% confidence interval [CI]: 3.4%-29.4%; P = 0.04) and T-type fractures (PD 28.7%; CI, 9.0%-48.9%; P = 0.001). Revision surgery was not found to be associated with age, body mass index, posterior wall fractures, concurrent pelvic ring fractures, or surgical approach. On radiographs, 51.3% (n = 76/148) had anatomic reductions (<2 mm) compared with only 10.2% (n = 15/148) on CT scans. CONCLUSIONS: Indications for revision of acetabular fixation surgeries and poor reductions were frequently missed on plain radiography and identified on postoperative CT scans. This suggests that the use of advanced imaging such as intraoperative 3D imaging or postoperative CT scans may be beneficial. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Should a history of pelvic fracture fixation be an indication for cesarean section?

PURPOSE: To compare the success rate of a trial of labor (TOL) in a cohort of patients with pelvic fractures, with and without internal fixation, in order to better counsel patients and avoid unnecessary cesarean section (CS). METHODS: A retrospective review of 35 female patients with 28 pelvic ring, five acetabular, and two combined fractures that had subsequent pregnancy; 12 patients had operative fixation and 23 did not. Fracture classification, treatment, type of fixation, mode of deliveries, and reason for CS were documented. RESULTS: The rate of vaginal delivery, unscheduled CS, and scheduled CS across all patients was 80.0% (n = 28), 14.3% (n = 5), and 5.7% (n = 2), respectively, which was similar to institutional rates of 87.0, 12.0, and 1.0%. A TOL was attempted in 91.4% (32/35) and successful in 87.5% (28/32). Patients who failed a TOL were more likely to have Tile B/C pelvic fractures (100.0 vs. 30.4%, observed difference (OD) 69.6%, 95% confidence interval (CI) 16.4, 86.3%; p = 0.01) and more pelvic displacement (6.0 vs. 1.5 mm, OD 4.0, CI 1.0, 18.0; p = 0.01). The fixation and control groups had no observed difference in successful TOL (72.7% vs. 95.2%, OD 22.5%, - 49.7%, 5.5%; p = 0.10). CONCLUSIONS: A majority of women had successful vaginal deliveries after pelvic fractures, with or without fixation, suggesting that these patients should consider a TOL. LEVEL OF EVIDENCE: Diagnostic Level III.

Use of 3D Printing Technology in Fracture Management: A Review and Case Series.

SUMMARY: Three-dimensional (3D) offers exciting opportunities in medicine, particularly in orthopaedics. The boundaries of 3D printing are continuously being re-established and have paved the way for further innovations, including 3D bioprinting, custom printing refined methods, 4D bioprinting, and 5D printing potential. The quality of these applications have been steadily improving, increasing their widespread use among clinicians. This article provides a review of the current literature with a brief introduction to the process of additive manufacturing, 3D printing, and its applications in fracture care. We illustrate this technology with a case series of 3D printing used for correction of complex fractures/nonunion. Factors limiting the use of this technology, including cost, and potential solutions are discussed. Finally, we discuss 4D bioprinting and 5D printing and their potential role in fracture surgery.

Conservative Management of Kienbock's Disease in a 7-year Old: A Case Report.

Background Kienbock's disease is primarily seen in young adult males but has been recognized in skeletally immature populations as well. Traditional treatment strategies recommend operative treatment but high remodeling potential in children may allow conservative management. Case Description We present the case of a 7-year-old female with 2 months of atraumatic right wrist pain who was found to have edematous signal change within the lunate on wrist magnetic resonance imaging (MRI) consistent with Kienbock's disease. She was treated with rigid immobilization for 12 weeks and transitioned to custom orthotic splint for another 3 months during activities. At her 6 month follow-up, she reported minimal wrist pain with repeat MRI demonstrating the resolution of lunate edema. Literature Review Available literature shows a significant portion of patients treated conservatively subsequently require surgical intervention due to unresolved symptoms or progressive disease. Only three cases are reported in the literature where skeletally immature patients were successfully treated with conservative management alone Clinical Relevance We report the youngest case of Lichtman stage I Kienbock's disease successfully treated with conservative management resulting in clinical and imaging resolution. Younger patients may be able to successfully remodel and recover from Kienbock disease with extended time in conservative management.

In-Office Diagnostic Needle Arthroscopy Using the NanoScope™ Arthroscopy System.

Diagnostic needle arthroscopy performed in office is a safe and cost-effective method for accurate evaluation of intra-articular pathology, improving clinical decision making. This minimally invasive approach is an effective alternative to traditional diagnostic techniques of diagnostic surgical arthroscopy and magnetic resonance imaging (MRI). Needle arthroscopy is considered low-risk, with an extremely low complication rate when performed with appropriate technique and indications. The purpose of this article is to describe an approach to an in-office diagnostic procedure using a needle arthroscopy system.

Sex-Based Differences in Adult ACL Reconstruction Outcomes.

PURPOSE OF REVIEW: In the setting of ever improving outcomes following anterior cruciate ligament (ACL) reconstruction, both objectively and subjectively, there remains continued interest in better understanding the differences in outcomes between male and female patients. The current review investigates the recent literature surrounding the roles of biological sex in adult ACL reconstruction outcomes. RECENT FINDINGS: Within the past five years, the most prominent and recurrent difference between male and female patient cohorts is the subjective report of pain and function. Female patients have been consistently shown to have worse self-reported outcomes following ACL reconstruction. Specific and quantifiable subjective outcomes that are highlighted include the International Knee Documentation Committee (IKDC) subjective score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and patient-acceptable symptom state (PASS). Current research on the topic of biological sex-based differences in ACL reconstruction outcomes can be divided into four main categories: patient-reported subjective outcomes; physical assessment and gait analysis; kinematics; and rates of reinjury, revision, and contralateral reconstruction. This chapter provides a summary of recent literature focused on these four main areas of interest related to ACL reconstruction outcomes in males and females.

SpeedBridge Knotless Double-Pulley Rotator Cuff Repair.

Rotator cuff tears remain a common injury, and may require rotator cuff repair, one of the most frequently performed orthopaedic procedures. Achieving an ideal construct during rotator cuff repair is crucial, and while many techniques exist to accomplish this, they are continuously evolving to improve stability and biomechanics of the repaired shoulder. Improving efficiency of the procedure alongside the increasing complexity of innovative techniques remains of the utmost importance. The double-pulley SpeedBridge technique achieves medial fixation in a double-row, transosseus-equivalent repair, and the knotless nature of the technique creates for a low-profile construct and improves overall efficiency. The purpose of this Technical Note is to describe a reproducible and efficient approach to arthroscopic rotator cuff repair using the SpeedBridge knotless double-pulley technique.

Incidence and Prevention of Thromboembolic Complications for Sports and Arthroscopic-related Surgery: Evidence-based Recommendations.

The incidence of thromboembolic events following arthroscopic surgery is relatively rare. Despite this, these are important complications to be aware of, as arthroscopic procedures are performed in high frequency each year and can lead to a substantial burden within health care. Over the past several decades, pharmacologic antithrombotic prevention strategies following knee arthroscopy have been extensively studied; however, their efficacy remains controversial, and there is a lack of consensus regarding a standard prevention protocol, with the exception of the established benefits of early mobilization. Several surgical and medical risk factors have been established and are important to consider as they specifically relate to each individual patient's risk of thromboembolic disease. Based on the best available evidence, chemical thromboprophylaxis appears to be unnecessary among healthy patients but may be beneficial for higher risk patients, especially those with a prior history of venous thromboembolism. A standard screening tool for risk factors in arthroscopy patients may be a cost-effective and safe solution for implementing preventative efforts.

Disseminated Nocardiosis Masquerading as Soft-Tissue Malignancy: A Case Report.

CASE: A 59-year-old man, immunosuppressed after renal transplant, presented with a painful posterior thigh mass concerning for malignancy, as well as pulmonary and posterior chest wall nodules. Cultures and mass spectrometry identified Nocardia paucivorans. The patient underwent operative irrigation and debridement of the posterior thigh and chest wall, with 12 months of antibiotic therapy. CONCLUSION: A 2-week delay in appropriate treatment was due to low suspicion for infectious etiology. Since cultures generally take weeks for positive diagnosis, advanced molecular or biochemical methods should be used. This case demonstrates importance in maintaining a high index of suspicion for nocardiosis in immunocompromised patients with soft-tissue masses.

Metal-on-metal total hip arthroplasty adverse local tissue reaction with intermittent unilateral vascular claudication.

Osteolysis and adverse local soft-tissue reactions are well-documented complications of metal-on-metal prosthetic implants. This case report describes a 68-year-old man who presented to the clinic 10 years after staged bilateral metal-on-metal total hip arthroplasty revisions with the primary complaint of groin pain, intermittent right leg pain, swelling, and muscle cramping while ambulating that resolved with rest. A complete workup was negative for deep venous thrombosis and infection. His symptoms were found to be secondary to an iliopsoas bursal mass externally compressing the femoral vasculature resulting in vascular claudication. He was treated with revision arthroplasty and drainage of the fluid within the iliopsoas bursal effusion with symptomatic resolution.

HSP90 inhibitors in the context of heat shock and the unfolded protein response: effects on a primary canine pulmonary adenocarcinoma cell line.

BACKGROUND: Agents targeting HSP90 and GRP94 are seldom tested in stressed contexts such as heat shock (HS) or the unfolded protein response (UPR). Tumor stress often activates HSPs and the UPR as pro-survival mechanisms. This begs the question of stress effects on chemotherapeutic efficacy, particularly with drugs targeting chaperones such as HSP90 or GRP94. We tested the utility of several HSP90 inhibitors, including PU-H71 (targeting GRP94), on a primary canine lung cancer line under HS/UPR stress compared to control conditions. METHODS: We cultured canine bronchoalveolar adenocarcinoma cells that showed high endogenous HSP90 and GRP94 expression; these levels substantially increased upon HS or UPR induction. We treated cells with HSP90 inhibitors 17-DMAG, 17-AAG or PU-H71 under standard conditions, HS or UPR. Cell viability/survival was assayed. Antibody arrays measured intracellular signalling and apoptosis profiles. RESULTS: HS and UPR had varying effects on cells treated with different HSP90 inhibitors; in particular, HS and UPR promoted resistance to inhibitors in short-term assays, but combinations of UPR stress and PU-H571 showed potent cytotoxic activity in longer-term assays. Array data indicated altered signalling pathways, with apoptotic and pro-survival implications. UPR induction + dual targeting of HSP90 and GRP94 swayed the balance toward apoptosis. CONCLUSION: Cellular stresses, endemic to tumors, or interventionally inducible, can deflect or enhance chemo-efficacy, particularly with chaperone-targeting drugs. Stress is likely not held accountable when testing new pharmacologics or assessing currently-used drugs. A better understanding of stress impacts on drug activities should be critical in improving therapeutic targeting and in discerning mechanisms of drug resistance.

An adverse event capture and management system for cancer studies.

BACKGROUND: Comprehensive capture of Adverse Events (AEs) is crucial for monitoring for side effects of a therapy while assessing efficacy. For cancer studies, the National Cancer Institute has developed the Common Terminology Criteria for Adverse Events (CTCAE) as a required standard for recording attributes and grading AEs. The AE assessments should be part of the Electronic Health Record (EHR) system; yet, due to patient-centric EHR design and implementation, many EHR's don't provide straightforward functions to assess ongoing AEs to indicate a resolution or a grade change for clinical trials. METHODS: At UAMS, we have implemented a standards-based Adverse Event Reporting System (AERS) that is integrated with the Epic EHR and other research systems to track new and existing AEs, including automated lab result grading in a regulatory compliant manner. Within a patient's chart, providers can launch AERS, which opens the patient's ongoing AEs as default and allows providers to assess (resolution/ongoing) existing AEs. In another tab, it allows providers to create a new AE. Also, we have separated symptoms from diagnoses in the CTCAE to minimize inaccurate designation of the clinical observations. Upon completion of assessments, a physician would submit the AEs to the EHR via a Health Level 7 (HL7) message and then to other systems utilizing a Representational State Transfer Web Service. CONCLUSIONS: AERS currently supports CTCAE version 3 and 4 with more than 65 cancer studies and 350 patients on those studies. This type of standard integrated into the EHR aids in research and data sharing in a compliant, efficient, and safe manner.

Exosome proteomics reveals transcriptional regulator proteins with potential to mediate downstream pathways.

Exosomes are virus-sized, membrane-enclosed vesicles with origins in the cellular endosomal system, but are released extracellularly. As a population, these tiny vesicles carry relatively enormous amounts of information in their protein, lipid and nucleic acid content, and the vesicles can have profound impacts on recipient cells. This review employs publically-available data combined with gene ontology applications to propose a novel concept, that exosomes transport transcriptional and translational machinery that may have direct impacts on gene expression in recipient cells. Here, we examine the previously published proteomic contents of medulloblastoma-derived exosomes, focusing on transcriptional regulators; we found that there are numerous proteins that may have potential roles in transcriptional and translational regulation with putative influence on downstream, cancer-related pathways. We expanded this search to all of the proteins in the Vesiclepedia database; using gene ontology approaches, we see that these regulatory factors are implicated in many of the processes involved in cancer initiation and progression. This information suggests that some of the effects of exosomes on recipient cells may be due to the delivery of protein factors that can directly and fundamentally change the transcriptional landscape of the cells. Within a tumor environment, this has potential to tilt the advantage towards the cancer.

Induction of the unfolded protein response drives enhanced metabolism and chemoresistance in glioma cells.

The unfolded protein response (UPR) is an endoplasmic reticulum (ER)-based cytoprotective mechanism acting to prevent pathologies accompanying protein aggregation. It is frequently active in tumors, but relatively unstudied in gliomas. We hypothesized that UPR stress effects on glioma cells might protect tumors from additional exogenous stress (ie, chemotherapeutics), postulating that protection was concurrent with altered tumor cell metabolism. Using human brain tumor cell lines, xenograft tumors, human samples and gene expression databases, we determined molecular features of glioma cell UPR induction/activation, and here report a detailed analysis of UPR transcriptional/translational/metabolic responses. Immunohistochemistry, Western and Northern blots identified elevated levels of UPR transcription factors and downstream ER chaperone targets in gliomas. Microarray profiling revealed distinct regulation of stress responses between xenograft tumors and parent cell lines, with gene ontology and network analyses linking gene expression to cell survival and metabolic processes. Human glioma samples were examined for levels of the ER chaperone GRP94 by immunohistochemistry and for other UPR components by Western blotting. Gene and protein expression data from patient gliomas correlated poor patient prognoses with increased expression of ER chaperones, UPR target genes, and metabolic enzymes (glycolysis and lipogenesis). NMR-based metabolomic studies revealed increased metabolic outputs in glucose uptake with elevated glycolytic activity as well as increased phospholipid turnover. Elevated levels of amino acids, antioxidants, and cholesterol were also evident upon UPR stress; in particular, recurrent tumors had overall higher lipid outputs and elevated specific UPR arms. Clonogenicity studies following temozolomide treatment of stressed or unstressed cells demonstrated UPR-induced chemoresistance. Our data characterize the UPR in glioma cells and human tumors, and link the UPR to chemoresistance possibly via enhanced metabolism. Given the role of the UPR in the balance between cell survival and apoptosis, targeting the UPR and/or controlling metabolic activity may prove beneficial for malignant glioma therapeutics.

Prolonged remission of advanced bronchoalveolar adenocarcinoma in a dog treated with autologous, tumour-derived chaperone-rich cell lysate (CRCL) vaccine.

PURPOSE: This paper presents the treatment of a 12-year-old female spayed Great Dane who presented with vestibular signs (ataxia, nystagmus, hind end collapse). Thoracic radiographs revealed a discrete pulmonary nodule in the right cranial lung lobe. Ultrasound-guided fine needle aspirate detected primary bronchoalveolar adenocarcinoma, verified via computed tomography, with a second smaller nodule discovered in the right cranial lung lobe. MATERIALS AND METHODS: A lateral thoracotomy with right cranial lung lobectomy was performed. Histopathological analysis of the nodules and an excised lymph node identified grade III bronchoalveolar adenocarcinoma with vascular infiltration and lymph node metastasis - a grim diagnosis with a reported median survival time of 6-27 days. A 10-g sample of the tumour was processed into a chaperone-rich cell lysate (CRCL) vaccine, which was administered weekly to the patient. Imiquimod - a Toll-like receptor 7 (TLR7) agonist - was applied topically for the first 12 treatments to stimulate local Langerhans cells. A single injection of bacillus Calmette-Guerin (BCG) was administered for additional immune stimulation at week 30 of treatment. RESULTS: The dog remained stable and in otherwise good health until diffuse relapse occurred 44 weeks after the initial treatment; following gastrointestinal bleeding, the dog was euthanised 50+ weeks post diagnosis. CONCLUSION: To the authors' knowledge, this is the first report of significantly prolonged survival following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a canine patient. This case report suggests that CRCL vaccine combined with topical imiquimod is a safe, effective treatment for canine tumours.