Wound infection following implant removal of foot, ankle, lower leg or patella; a protocol for a multicenter randomized controlled trial investigating the (cost-)effectiveness of 2 g of prophylactic cefazolin compared to placebo (WIFI-2 trial).

BACKGROUND: Elective implant removal (IR) after fracture fixation is one of the most common procedures within (orthopedic) trauma surgery. The rate of surgical site infections (SSIs) in this procedure is quite high, especially below the level of the knee. Antibiotic prophylaxis is not routinely prescribed, even though it has proved to lower SSI rates in other (orthopedic) trauma surgical procedures. The primary objective is to study the effectiveness of a single intravenous dose of 2 g of cefazolin on SSIs after IR following fixation of foot, ankle and/or lower leg fractures. METHODS: This is a multicenter, double-blind placebo controlled trial with a superiority design, including adult patients undergoing elective implant removal after fixation of a fracture of foot, ankle, lower leg or patella. Exclusion criteria are: an active infection, current antibiotic treatment, or a medical condition contraindicating prophylaxis with cefazolin including allergy. Patients are randomized to receive a single preoperative intravenous dose of either 2 g of cefazolin or a placebo (NaCl). The primary analysis will be an intention-to-treat comparison of the proportion of patients with a SSI at 90 days after IR in both groups. DISCUSSION: If 2 g of prophylactic cefazolin proves to be both effective and cost-effective in preventing SSI, this would have implications for current guidelines. Combined with the high infection rate of IR which previous studies have shown, it would be sufficiently substantiated for guidelines to suggest protocolled use of prophylactic antibiotics in IR of foot, ankle, lower leg or patella. Trial registration Nederlands Trial Register (NTR): NL8284, registered on 9th of January 2020, https://www.trialregister.nl/trial/8284.

An ex vivo Tissue Culture Model for the Assessment of Individualized Drug Responses in Prostate and Bladder Cancer.

Urological malignancies, including prostate and bladder carcinoma, represent a major clinical problem due to the frequent occurrence of therapy resistance and the formation of incurable distant metastases. As a result, there is an urgent need for versatile and predictive disease models for the assessment of the individualized drug response in urological malignancies. Compound testing on ex vivo cultured patient-derived tumor tissues could represent a promising approach. In this study, we have optimized an ex vivo culture system of explanted human prostate and bladder tumors derived from clinical specimens and human cancer cell lines xenografted in mice. The explanted and cultured tumor slices remained viable and tissue architecture could be maintained for up to 10 days of culture. Treatment of ex vivo cultured human prostate and bladder cancer tissues with docetaxel and gemcitabine, respectively, resulted in a dose-dependent anti-tumor response. The dose-dependent decrease in tumor cells upon administration of the chemotherapeutic agents was preceded by an induction of apoptosis. The implementation and optimization of the tissue slice technology may facilitate the assessment of anti-tumor efficacies of existing and candidate pharmacological agents in the complex multicellular neoplastic tissues from prostate and bladder cancer patients. Our model represents a versatile "near-patient" tool to determine tumor-targeted and/or stroma-mediated anti-neoplastic responses, thus contributing to the field of personalized therapeutics.

Computed tomography versus magnetic resonance imaging versus bone scintigraphy for clinically suspected scaphoid fractures in patients with negative plain radiographs.

BACKGROUND: In clinically suspected scaphoid fractures, early diagnosis reduces the risk of non-union and minimises loss in productivity resulting from unnecessary cast immobilisation. Since initial radiographs do not exclude the possibility of a fracture, additional imaging is needed. Computed tomography (CT), magnetic resonance imaging (MRI) and bone scintigraphy (BS) are widely used to establish a definitive diagnosis, but there is uncertainty about the most appropriate method. OBJECTIVES: The primary aim of this study is to identify the most suitable diagnostic imaging strategy for identifying clinically suspected fractures of the scaphoid bone in patients with normal radiographs. Therefore we looked at the diagnostic performance characteristics of the most used imaging modalities for this purpose: computed tomography, magnetic resonance imaging and bone scintigraphy. SEARCH METHODS: In July 2012, we searched the Cochrane Register of Diagnostic Test Accuracy Studies, MEDLINE, EMBASE, the Database of Abstracts of Reviews of Effects, the Cochrane Central Register of Controlled Trials, the NHS Economic Evaluation Database. In September 2012, we searched MEDION, ARIF, Current Controlled Trials, the World Health Organization (WHO) International Clinical Trials Registry Platform, conference proceedings and reference lists of all articles. SELECTION CRITERIA: We included all prospective or retrospective studies involving a consecutive series of patients of all ages that evaluated the accuracy of BS, CT or MRI, or any combination of these, for diagnosing suspected scaphoid fractures. We considered the use of one or two index tests or six-week follow-up radiographs as adequate reference standards. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and assessed full-text reports of potentially eligible studies. The same authors extracted data from full-text reports and assessed methodological quality using the QUADAS checklist. For each index test, estimates of sensitivity and specificity from each study were plotted in ROC space; and forest plots were constructed for visual examination of variation in test accuracy. We performed meta-analyses using the HSROC model to produce summary estimates of sensitivity and specificity. MAIN RESULTS: We included 11 studies that looked at diagnostic accuracy of one or two index tests: four studies (277 suspected fractures) looked at CT, five studies (221 suspected fractures) looked at MRI and six studies (543 suspected fractures) looked at BS. Four of the studies made direct comparisons: two studies compared CT and MRI, one study compared CT and BS, and one study compared MRI and BS. Overall, the studies were of moderate to good quality, but relevant clinical information during evaluation of CT, MRI or BS was mostly unclear or unavailable.As few studies made direct comparisons between tests with the same participants, our results are based on data from indirect comparisons, which means that these results are more susceptible to bias due to confounding. Nonetheless, the direct comparisons showed similar patterns of differences in sensitivity and specificity as for the pooled indirect comparisons.Summary sensitivity and specificity of CT were 0.72 (95% confidence interval (CI) 0.36 to 0.92) and 0.99 (95% CI 0.71 to 1.00); for MRI, these were 0.88 (95% CI 0.64 to 0.97) and 1.00 (95% CI 0.38 to 1.00); for BS, these were 0.99 (95% CI 0.69 to 1.00) and 0.86 (95% CI 0.73 to 0.94). Indirect comparisons suggest that diagnostic accuracy of BS was significantly higher than CT and MRI; and CT and MRI have comparable diagnostic accuracy. The low prevalence of a true fracture among suspected fractures (median = 20%) means the lower specificity for BS is problematic. For example, in a cohort of 1000 patients, 112 will be over-treated when BS is used for diagnosis. If CT is used, only 8 will receive unnecessary treatment. In terms of missed fractures, BS will miss 2 fractures and CT will miss 56 fractures. AUTHORS' CONCLUSIONS: Although quality of the included studies is moderate to good, findings are based on only 11 studies and the confidence intervals for the summary estimates are wide for all three tests. Well-designed direct comparison studies including CT, MRI and BS could give valuable additional information.Bone scintigraphy is statistically the best diagnostic modality to establish a definitive diagnosis in clinically suspected fractures when radiographs appear normal. However, physicians must keep in mind that BS is more invasive than the other modalities, with safety issues due to level of radiation exposure, as well as diagnostic delay of at least 72 hours. The number of overtreated patients is substantially lower with CT and MRI.Prior to performing comparative studies, there is a need to raise the initially detected prevalence of true fractures in order to reduce the effect of the relatively low specificity in daily practice. This can be achieved by improving clinical evaluation and initial radiographical assessment.

Fracture surgery of the extremities with the intra-operative use of 3D-RX: a randomized multicenter trial (EF3X-trial).

BACKGROUND: Posttraumatic osteoarthritis can develop after an intra-articular extremity fracture, leading to pain and loss of function. According to international guidelines, anatomical reduction and fixation are the basis for an optimal functional result. In order to achieve this during fracture surgery, an optimal view on the position of the bone fragments and fixation material is a necessity. The currently used 2D-fluoroscopy does not provide sufficient insight, in particular in cases with complex anatomy or subtle injury, and even an 18-26% suboptimal fracture reduction is reported for the ankle and foot. More intra-operative information is therefore needed.Recently the 3D-RX-system was developed, which provides conventional 2D-fluoroscopic images as well as a 3D-reconstruction of bony structures. This modality provides more information, which consequently leads to extra corrections in 18-30% of the fracture operations. However, the effect of the extra corrections on the quality of the anatomical fracture reduction and fixation as well as on patient relevant outcomes has never been investigated.The objective of this study protocol is to investigate the effectiveness of the intra-operative use of the 3D-RX-system as compared to the conventional 2D-fluoroscopy in patients with traumatic intra-articular fractures of the wrist, ankle and calcaneus. The effectiveness will be assessed in two different areas: 1) the quality of fracture reduction and fixation, based on the current golden standard, Computed Tomography. 2) The patient-relevant outcomes like functional outcome range of motion and pain. In addition, the diagnostic accuracy of the 3D-RX-scan will be determined in a clinical setting and a cost-effectiveness as well as a cost-utility analysis will be performed. METHODS/DESIGN: In this protocol for an international multicenter randomized clinical trial, adult patients (age > 17 years) with a traumatic intra-articular fracture of the wrist, ankle or calcaneus eligible for surgery will be subjected to additional intra-operative 3D-RX. In half of the patients the surgeon will be blinded to these results, in the other half the surgeon may use the 3D-RX results to further optimize fracture reduction. In both randomization groups a CT-scan will be performed postoperatively. Based on these CT-scans the quality of fracture reduction and fixation will be determined. During the follow-up visits after hospital discharge at 6 and 12 weeks and 1 year postoperatively the patient relevant outcomes will be determined by joint specific, health economic and quality of life questionnaires. In addition a follow up study will be performed to determine the patient relevant outcomes and prevalence of posttraumatic osteoarthritis at 2 and 5 years postoperatively. DISCUSSION: The results of the study will provide more information on the effectiveness of the intra-operative use of 3D-imaging during surgical treatment of intra-articular fractures of the wrist, ankle and calcaneus. A randomized design in which patients will be allocated to a treatment arm during surgery will be used because of its high methodological quality and the ability to detect incongruences in the reduction and/or fixation that occur intra-operatively in the blinded arm of the 3D-RX. An alternative, pragmatic design could be to randomize before the start of the surgery, then two surgical strategies would be compared. This resembles clinical practice better, but introduces more bias and does not allow the assessment of incongruences that would have been detected by 3D-RX in the blinded arm. TRIAL REGISTRATION: Dutch Trial Register NTR 1902.

MRI assessment of the posterior acetabular wall fracture in traumatic dislocation of the hip in children.

Traumatic hip dislocations associated with posterior wall fractures of the acetabulum in the pediatric population are in general a consequence of high-energy trauma. After expeditious reduction, instability mandates for further diagnosis and intervention. Plain radiographs or computerized tomography (CT) scans can misjudge the involvement of the posterior wall of the acetabulum due to the partially calcified nature of the pediatric bone. We present two cases of pediatric traumatic hip dislocation associated with posterior wall fractures of the acetabulum. In both cases, obvious postreduction instability was noted without conclusive findings of etiology on plain X-rays or CT scans. Magnetic resonance imaging (MRI) disclosed an extensive posterior wall traumatic involvement in both cases and helped to decide in favor of open reduction of the hip and internal fixation of the posterior wall fragment.