Preoperative Symptoms in Femoroacetabular Impingement Patients Are More Related to Mental Health Scores Than the Severity of Labral Tear or Magnitude of Bony Deformity.

BACKGROUND: The purpose of this study was to determine the relationships between patient factors, mental health status, the condition of the local tissue, magnitude of bony deformity, and preoperative symptoms in a series of femoroacetabular impingement (FAI) patients. METHODS: From our prospective outcomes registry, we identified 64 patients with arthroscopically-treated labral tears and cam deformities. We assessed the correlations between patient factors (age, sex, body mass index, level of education), surgical findings (size of labral tear, presence of chondral lesions), mental health factors (VR-12 mental component score [MCS], depression, and preoperative use of psychotropic and/or opioid drugs), magnitude of FAI deformity (alpha and lateral center edge angles), and preoperative hip dysfunction and osteoarthritis outcome score (HOOS) subscales. Patient factors, surgical and radiographic findings, and preoperative HOOS scores were compared between patients with low and high MCS. RESULTS: Neither hip pathology nor patient-related factors significantly correlated with HOOS scores. On the contrary, MCS significantly correlated with HOOS symptom (ρ = 0.45, P < .001) and pain scores (ρ = 0.52, P < .001). Low MCS patients had significantly lower preoperative scores for all 5 HOOS subscales (P ≤ .002) and more frequent chondral lesions and comorbid depression (P ≤ .01). CONCLUSION: Symptom severity was significantly more related to mental health status than either the size of labral tear or FAI deformity. Patients with low MCS had significantly worse preoperative pain and self-reported function, and a greater prevalence of concomitant chondral lesions. Future studies are necessary to determine if earlier surgical treatment or preoperative psychological and/or pain coping interventions may improve outcomes for those with low MCS.

Dendritic cell vaccination combined with temozolomide retreatment: results of a phase I trial in patients with recurrent glioblastoma multiforme.

There is no standard treatment for recurrent glioblastoma multiforme (GBM). Retreatment with temozolomide (TMZ) is one treatment option. We reasoned this could be more effective if combined with a vaccine that preferentially targeted TMZ-resistant cells. To test the feasibility and safety of such an approach, a phase 1 trial was conducted in which patients with GBM tumors relapsing after standard chemoradiotherapy were retreated with TMZ in combination with a vaccine consisting of monocyte-derived dendritic cells (DC) pulsed with autologous tumor cells that had previously been exposed to TMZ in vivo in the course of primary treatment. Of 14 participants, nine patients completed the initial phase of priming vaccinations and two cycles of TMZ, one proved to have radionecrosis, one rapidly progressed, and in three the yield of DC vaccine was insufficient to proceed with treatment. Other than expected toxicities related to TMZ, there were no adverse events attributable to the combined treatment. Two patients had objective radiological responses. Six month progression-free survival was 22 %, similar to retreatment with TMZ alone. Anti-tumor immune responses were assessed in peripheral blood mononuclear cells using interferon-γ ELISpot, with two patients meeting criteria for a vaccine-induced immune response, one of whom remained disease-free for nearly three years. Another patient with an anti-tumor immune response at baseline that was sustained post-vaccination experienced a 12-month period of progression-free survival. In summary, the combined treatment was safe and well-tolerated but feasibility in the recurrent setting was marginal. Evidence of immune responses in a few patients broadly correlated with better clinical outcome.

Lyophilizer Leak Rate Testing - An Industry Survey and Best Practice Recommendation.

The vacuum integrity of freeze dryers is critical for attaining adequate process control and maintaining confidence in sterility assurance which is key for the manufacture of sterile pharmaceutical products. Although discussions on the topic have been published, there is no industry standard established that is based on empirical data or that has a justifiable scientific rationale. This article provides a review of the scientific literature in the public domain and most importantly, a perspective from 14 Pharmaceutical companies on the leak rate specifications commonly used in industry. Using this information we recommend a best practice for the lyophilizer leak rate test which includes detailing necessary preparation activities following Steam-In-Place (SIP) sterilization, defining a period of stabilization to eliminate pressure and temperature fluctuations and details of the test conditions and the test period. We conclude that for routine manufacturing practice the operational leak rate should not exceed 20 µbar L/s and we provide additional guidance for large volume and older lyophilisation equipment.

The Learning Curve of Suprapatellar Nailing: Adoption Over Time Can Decrease Operative Time and Radiation Exposure.

OBJECTIVE: To determine whether suprapatellar nailing (SPN) over time can decrease operative time and radiation exposure when compared with infrapatellar nailing (IPN) of tibial shaft fractures. DESIGN: Retrospective. SETTING: Single, Level 1 trauma center. PATIENTS: Extra-articular adult tibial shaft fractures treated with intramedullary nailing alone within a 7-year period. INTERVENTION: Patients were treated with SPN or IPN techniques based on the discretion of the operating surgeon. MAIN OUTCOME MEASUREMENTS: Operative time and radiation exposure. RESULTS: Three hundred forty-one fractures (SPN: 177, IPN: 164) were included in the analysis. No differences in patient body mass index, sex, or open fracture incidence existed between the 2 groups. A significant difference in average operative time (IPN 130 minutes vs. SPN 110 minutes, P < 0.01), fluoroscopy time (IPN 159 minutes vs. SPN 143 minutes, P = 0.02), and radiation dose (IPN 8.6 mGy vs. SPN 6.5 mGy, P < 0.01) existed between IPN and SPN. Early tibias treated with SPN had similar operative times (P = 0.11), fluoroscopy time (P = 0.94), and radiation dose (P = 0.34) compared with IPN. Later SPN patients had significantly lower operative time (P = 0.03), fluoroscopy time (P < 0.01), and radiation dose (P < 0.013) compared with earlier SPN. Regression analysis revealed with the increased use of SPN, operative time, fluoroscopy time, and radiation dose significantly decreased (P = 0.018, 0.046, 0.011). CONCLUSIONS: Tibia fractures treated with SPN have significantly decreased operative times and radiation exposure compared with those treated with IPN, after allowing time for the surgeon to gain sufficient experience with the technique. The surgeon should consider this when deciding to adopt this technique. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Monitoring anatomical changes of individual patients using statistical process control during head-and-neck radiotherapy.

BACKGROUND AND PURPOSE: Reduced toxicity while maintaining loco-regional control rates have been reported after reducing planning target volume (PTV) margins for head-and-neck radiotherapy (HNRT). In this context, quantifying anatomical changes to monitor patient treatment is preferred. This retrospective feasibility study investigated the application of deformable image registration (DIR) and Exponentially Weighted Moving Average (EWMA) Statistical Process Control (SPC) charts for this purpose. MATERIALS AND METHODS: DIR between the computed tomography for treatment planning (pCT) images of twelve patients and their daily on-treatment cone beam computed tomography (CBCT) images quantified anatomical changes during treatment. EWMA charts investigated corresponding trends. Uncertainty analysis provided 90% confidence limits which were used to confirm whether a trend previously breached a threshold. RESULTS: Trends in patient positioning reproducibility occurred before the end of treatment week four in 54% of cases. Using SPC process limits, only 24% of these were confirmed at a 90% confidence level before the end of treatment. Using an a priori clinical limit of 2 mm, absolute changes in patient pose were detected in 39% of cases, of which 82% were confirmed. Soft tissue trends outside SPC process limits occurring before the end of treatment week four were confirmed in 90% of cases. CONCLUSION: Structure specific action thresholds enabled detection of systematic anatomical changes during the first four weeks of treatment. Investigation of the dosimetric impact of the observed deviations is needed to show the efficacy of SPC to timely indicate required treatment adaptation and provide a safety net for PTV margin reduction.

Comminuted olecranon fracture fixation with pre-contoured plate: Comparison of composite and cadaver bones.

AIM: To determine whether use of a precontoured olecranon plate provides adequate fixation to withstand supraphysiologic force in a comminuted olecranon fracture model. METHODS: Five samples of fourth generation composite bones and five samples of fresh frozen human cadaveric left ulnae were utilized for this study. The cadaveric specimens underwent dual-energy X-ray absorptiometry (DEXA) scanning to quantify the bone quality. The composite and cadaveric bones were prepared by creating a comminuted olecranon fracture and fixed with a pre-contoured olecranon plate with locking screws. Construct stiffness and failure load were measured by subjecting specimens to cantilever bending moments until failure. Fracture site motion was measured with differential variable resistance transducer spanning the fracture. Statistical analysis was performed with two-tailed Mann-Whitney-U test with Monte Carlo Exact test. RESULTS: There was a significant difference in fixation stiffness and strength between the composite bones and human cadaver bones. Failure modes differed in cadaveric and composite specimens. The load to failure for the composite bones (n = 5) and human cadaver bones (n = 5) specimens were 10.67 nm (range 9.40-11.91 nm) and 13.05 nm (range 12.59-15.38 nm) respectively. This difference was statistically significant (P ˂ 0.007, 97% power). Median stiffness for composite bones and human cadaver bones specimens were 5.69 nm/mm (range 4.69-6.80 nm/mm) and 7.55 nm/mm (range 6.31-7.72 nm/mm). There was a significant difference for stiffness (P ˂ 0.033, 79% power) between composite bones and cadaveric bones. No correlation was found between the DEXA results and stiffness. All cadaveric specimens withstood the physiologic load anticipated postoperatively. Catastrophic failure occurred in all composite specimens. All failures resulted from composite bone failure at the distal screw site and not hardware failure. There were no catastrophic fracture failures in the cadaveric specimens. Failure of 4/5 cadaveric specimens was defined when a fracture gap of 2 mm was observed, but 1/5 cadaveric specimens failed due to a failure of the triceps mechanism. All failures occurred at forces greater than that expected in postoperative period prior to healing. CONCLUSION: The pre-contoured olecranon plate provides adequate fixation to withstand physiologic force in a composite bone and cadaveric comminuted olecranon fracture model.

Validation of Varian's SmartAdapt® deformable image registration algorithm for clinical application.

BACKGROUND: Re-contouring of structures on consecutive planning computed tomography (CT) images for patients that exhibit anatomical changes is elaborate and may negatively impact the turn-around time if this is required for many patients. This study was therefore initiated to validate the accuracy and usefulness of automatic contour propagation for head and neck cancer patients using SmartAdapt® which is the deformable image registration (DIR) application in Varian's Eclipse™ treatment planning system. METHODS: CT images of eight head and neck cancer patients with multiple planning CTs were registered using SmartAdapt®. The contoured structures of target volumes and OARs of the primary planning CT were deformed accordingly and subsequently compared with a reference structure set being either: 1) a structure set independently contoured by the treating Radiation Oncologist (RO), or 2) the DIR-generated structure set after being reviewed and modified by the RO. RESULTS: Application of DIR offered a considerable time saving for ROs in delineation of structures on CTs that were acquired mid-treatment. Quantitative analysis showed that 84% of the volume of the DIR-generated structures overlapped with the independently re-contoured structures, while 94% of the volume overlapped with the DIR-generated structures after review by the RO. This apparent intra-observer variation was further investigated resulting in the identification of several causes. Qualitative analysis showed that 92% of the DIR-generated structures either need no or only minor modification during RO reviews. CONCLUSIONS: SmartAdapt is a powerful tool with sufficient accuracy that saves considerable time in re-contouring structures on re-CTs. However, careful review of the DIR-generated structures is mandatory, in particular in areas where tumour regression plays a role.

A prospective, controlled evaluation of the abdominal reapproximation anchor abdominal wall closure system in combination with VAC therapy compared with VAC alone in the management of an open abdomen.

Dramatic increases in damage control and decompressive laparotomies and a significant increase in patients with open abdominal cavities have resulted in numerous techniques to facilitate fascial closure. We hypothesized addition of the abdominal reapproximation anchor system (ABRA) to the KCI Abdominal Wound Vac™ (VAC) or KCI ABThera™ would increase successful primary closure rates and reduce operative costs. Fourteen patients with open abdomens were prospectively randomized into a control group using VAC alone (control) or a study group using VAC plus ABRA (VAC-ABRA). All patients underwent regular VAC changes; patients receiving VAC-ABRA also underwent concomitant daily elastomer adjustment of the ABRA system. Primary end points included abdominal closure, number of operating room (OR) visits, and OR time use. Eight patients were included in the VAC-ABRA group and six patients in the control group. Primary closure rates between groups were not statistically different; however, the number of trips to the OR and OR time use were different. Despite higher Acute Physiology and Chronic Health Evaluation II scores, larger starting wound size, and higher rates of abdominal compartment syndrome, closure rates in the VAC-ABRA group were similar to VAC alone. Importantly, however, fewer OR trips and less OR time were required for the VAC-ABRA group.

Emerging therapeutics targeting castration-resistant prostate cancer: the AR-mageddon of tumor epithelial-mesenchymal transition.

Advanced prostate cancer will claim nearly 30,000 lives among men in the USA in the year 2013. Most of these will be castration-resistant prostate cancers that are not responsive to traditional therapeutic modalities, and there is no available regimen that fully eradicates metastatic disease. This poses a significant clinical challenge for practitioners and has stimulated the development of novel agents that target these castration-resistant tumor cells. Development of metastatic prostate cancer is orchestrated by multiple signaling pathways that regulate cell survival, apoptosis, anoikis, epithelial-mesenchymal transition (EMT), invasion, the androgen signaling axis and angiogenesis. Disruption of the mechanisms underlying these processes is critical for development of agents that can target otherwise resistant tumor cells. Insights into the mechanisms by which rounds of EMT/mesenchymal-epithelial transition conversions facilitate the progression of localized prostate carcinomas to advanced metastatic and castration-resistant disease emerge as attractive targets for drug development. In this review, the authors discuss the current understanding of therapeutic resistance in castration-resistant prostate cancer with focus on the androgen receptor signaling axis and EMT. Novel therapeutic approaches targeting critical players of both pathways as well as the results from ongoing clinical trials will be discussed in this review.

Use of the obturator-outlet oblique view to guide percutaneous retrograde posterior column screw placement.

In contrast to open reduction internal fixation, percutaneous fixation is a relatively new option for operative fixation of acetabular fractures. The techniques for percutaneous insertion of anterior and posterior column screws have been previously described. For technical aspects of retrograde percutaneous posterior column screws, much attention has been paid to the proper start point. However, descriptions of proper trajectory and end point have not been as clearly delineated. Understanding of posterior column anatomy and its radiographic correlates are fundamental in the safe placement of this screw. Herein, we present technical advice for acquisition and interpretation of fluoroscopic images needed to ensure a safe trajectory and end point in retrograde percutaneous posterior column screw placement. We highlight our steps to ensure correct placement in a small series.

Bilateral asymmetric hip dislocation: A case series and literature review of a rare injury pattern.

BACKGROUND: Bilateral asymmetric hip dislocation, with one hip dislocated posteriorly and with anterior dislocation of the contralateral hip, is a rare injury pattern. A total of 34 cases have been reported in English literature, but only 24 cases detail injury mechanism and patient demographic factors, 3 of which reported bilateral asymmetric hip dislocation in female patients. Only one report describes more than one example. We describe four patients with bilateral asymmetric hip dislocation, including one example in a female patient, which represents the largest case series to date. Pertinent anatomy, injury mechanism, treatment options, and prognosis are also discussed. METHODS: A literature review was conducted via PubMed using the term bilateral asymmetric dislocation. Review of additional reports cited by articles found by our search resulted in what we think to be an exhaustive list of cases reported to date.A medical record review of four patients treated at our institution, a Level I trauma center, was performed to compare our treatment methods and outcomes to those previously described. RESULTS: All four patients in our case series had satisfactory outcomes. Motor vehicle collision is the most common cause of bilateral asymmetric hip dislocation. CONCLUSION: Timely, accurate reduction of bilateral asymmetric hip dislocation is recommended for optimal outcomes. An understanding of pertinent anatomy about the hip joint allows the orthopedic surgeon to perform a safe, timely reduction. In the absence of an associated acetabular fracture, conservative management with weight-bearing restrictions typically leads to good outcomes without complications such as aseptic necrosis of the femoral head. LEVEL OF EVIDENCE: Therapeutic study, level V.