ACR Appropriateness Criteria® Chronic Hip Pain: 2022 Update.

Chronic hip pain is a frequent chief complaint for adult patients who present for evaluation in a variety of clinical practice settings. Following a targeted history and physical examination, imaging plays a vital role in elucidating the etiologies of a patient's symptoms, as a wide spectrum of pathological entities may cause chronic hip pain. Radiography is usually the appropriate initial imaging test following a clinical examination. Depending on the clinical picture, advanced cross-sectional imaging may be subsequently performed for further evaluation. This documents provides best practice for the imaging workup of chronic hip pain in patients presenting with a variety of clinical scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Workplace Hazards in Orthopaedic Surgery Training: A Nationwide Resident Survey Involving Sharps-related Injuries.

INTRODUCTION: Surgical specialties are at an increased risk for occupational hazards, including sharps-related injuries. The objective of this study was to report the frequency of sharps injuries and evaluate which characteristics influence the number of injuries and reporting behaviors. METHODS: A web-based, anonymous survey was available for 10 weeks to 46 US orthopaedic surgery residency programs (1,207 potential residents) participating in an education research collaborative. The survey was divided into the following areas: demographics, training and attitudes concerning occupational hazards, and sharps injuries and reporting. Logistic regression was used to evaluate the association between the above variables on experiencing sharps injuries with significance threshold set at P < 0.05. RESULTS: In this study, 518 surveys were included yielding a response rate of 42.9% (518/1,207). Nearly 80% of the residents recalled some form of safety training during intern orientation and 62% of the respondents felt that they received adequate occupation safety training specifically related to orthopaedic surgery. Four hundred seventeen residents (80.5%) experienced a sharps injury (mean 2.8). Nearly 20% of the respondents experienced ≥5 sharps injuries. Needle sticks (38.8%) were responsible for the greatest percentage of injuries, followed by Kirschner wires (33.6%), scalpel (22.5%), and bone (17.3%). Only 42% of the residents consistently reported all injuries. Reasons included feelings of no risk (63.1%), too much hassle (58.9%), embarrassment (14.5%), other (8.7%), forgot (5.8%), and unclear what to do (3.3%). Inadequate safety training specific to orthopaedic surgery (odds ratio, 2.32 [95% confidence interval, 1.20 to 4.46]; P = 0.012) and greater training seniority (odds ratio, 2.04 [95% confidence interval, 1.64 to 2.52]; P < 0.0001) were associated with acquiring five or more sharps injuries. DISCUSSION: Sharps injuries are a prevalent and concerning reality for orthopaedic surgical trainees. Despite this common occurrence, only 42% of the residents always reported their injuries. Inadequate training specific to orthopaedic surgery and each subsequent year of postgraduate training are associated with increased sharps injuries. STUDY TYPE: Level III, retrospective observational survey.

Acute Workplace Hazards in Orthopedic Surgery: Resident Survey Regarding Splash and Workplace Violence Events.

INTRODUCTION: Orthopedic surgery residents are at risk for daily work-related hazards and exposures. Hazards related specific to this specialty includes radiation exposure, smoke inhalation (from electrocautery), and disease transmission through contact with surgical instruments or sharps during procedures. However, minimal research has been focused on other occupational hazard risks in orthopedic surgery including surgical splash events and workplace violence. This study focused on determining (1) whether or not use of protective eyewear in the workplace would be related to the availability of personal protective equipment (PPE); (2) resident education; and (3) the rate of workplace violence toward orthopedic surgery residents during their training. METHODS: An invitation to participate in a web-based, anonymous survey to 46 US allopathic orthopedic surgery residency programs (1207 potential resident respondents). The survey was conceptually divided into the following areas: (1) demographics; (2) training and attitudes concerning occupational hazards; (3) PPE provision and use; (4) sharps injuries and reporting; and (5) general safety knowledge and violence in the workplace. Those who answered yes to having a splatter event or receiving a threat at the hospital were compared to those who did not. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between these outcomes and selected independent variables of interest. p-Values of <0.05 were considered statistically significant. RESULTS: From January 18 to March 31, 2016, 518 surveys were received and included for analysis for a response rate of 42.9% (518/1207). One survey was excluded from analysis due to <50% completed response items. Self-reported program types were 64.5% (334/518) public university-affiliated, 23.2% (120/518) private university affiliated, 7.1% (37/518) community, and 5.2% (27/518) military. Residents were 83.0% = male and 17.0% = female. Overall, reported eye protection usage was 95% amongst all residents and 22% of residents reported experiencing a violent threat in the workplace. The risk of experiencing a splatter event was not statistically associated with residency type, gender, or geographic region. Senior residents were at an increased likelihood of experiencing a splatter event (OR 1.22, [95% CI 1.06-1.41], p = 0.006) when compared to PGY-1 residents. The risk of a violent experience at work was not statistically associated with residency type, year of residency training, or gender. Residents in the Northeast were more likely to have a violent experience (OR 2.78 [95% CI 1.41-5.49] p = 0.003). Overall, residents felt that they had adequate training to prevent occupational hazards (mean of 3.9/5 on Likert scale) and respond to hazards (mean of 3.7/5 Likert). CONCLUSIONS: Occupational hazards are not uncommon in orthopedic surgery training with high rates of improper eyewear PPE use and poor awareness of Occupational Safety and Health Administration and AAOS guidelines. Violence in the workplace impacts over one in 4 residents and training programs and hospitals should improve education and report efforts. Continual yearly PPE training and awareness of AAOS guidelines could be intertwined with duty hour and/or case logs in order to ensure residents are exposed to this material on a regular basis.

Diagnosis and Prevention of Periprosthetic Joint Infections.

The Diagnosis and Prevention of Periprosthetic Joint Infections Clinical Practice Guideline is based on a systematic review of current scientific and clinical research. Through analysis of the current best evidence, this guideline seeks to evaluate strategies to mitigate the risk of periprosthetic joint infection (PJI) in hip and knee arthroplasty and identify best practices in the diagnostic evaluation for these infections. Twenty-five recommendations related to prevention and diagnosis of PJI are presented. In addition, the work group highlighted areas for needed additional research when evidence proved lacking on the topic and carefully reviewed the rationale behind the recommendations while also noting potential harms or risks associated with implementation.

Correction: Alterations in Wnt- and/or STAT3 signaling pathways and the immune microenvironment during metastatic progression.

The original version of this Article incorrectly matched the supplementary files with their titles. This has been corrected. The following information has also been added to the Methods section.

Alterations in Wnt- and/or STAT3 signaling pathways and the immune microenvironment during metastatic progression.

Metastatic breast cancer is an extremely complex disease with limited treatment options due to the lack of information about the major characteristics of metastatic disease. There is an urgent need, therefore, to understand the changes in cellular complexity and dynamics that occur during metastatic progression. In the current study, we analyzed the cellular and molecular differences between primary tumors and paired lung metastases using a syngeneic p53-null mammary tumor model of basal-like breast cancer. Distinct subpopulations driven by the Wnt- and/or STAT3 signaling pathways were detected in vivo using a lentiviral Wnt- and STAT3 signaling reporter system. A significant increase in the overlapping populations driven by both the Wnt- and STAT3 signaling pathways was observed in the lung metastases as compared to the primary tumors. Furthermore, the overlapping populations showed a higher metastatic potential relative to the other populations and pharmacological inhibition of both signaling pathways was shown to markedly reduce the metastatic lesions in established lung metastases. An analysis of the unique molecular features of the lung metastases revealed a significant association with immune response signatures. Specifically, Foxp3 gene expression was markedly increased and elevated levels of Foxp3 + Treg cells were detected in close proximity to lung metastases. Collectively, these studies illustrate the importance of analyzing intratumoral heterogeneity, changes in population dynamics, and the immune microenvironment during metastatic progression.

Intramuscular infiltration of a local anesthetic, lidocaine, does not result in adverse behavioural side effects in rainbow trout.

Fish are a useful animal model for research, but our improvement in some aspects of their welfare has not kept pace with their increased popularity for this use. For example, researchers rarely use analgesics. We evaluated the side effects of lidocaine, a local anesthetic widely used in human and veterinary medicine. We infiltrated lidocaine on each side of the dorsal fin (total 20 mg/kg) of young rainbow trout (15 fish per group) compared with infiltration with an equal volume of saline. We monitored behaviour of individual trout during the 4-hour trial. Food was presented 5 times during the trial (30 min, 1 h, 2 h, 3 h, 4 h after infiltration) and we analyzed behaviour for 1 minute before and after food presentation. Behaviour of Saline-Infiltrated trout compared with trout that received no infiltration showed that infiltration in and of itself had no statistically significant effects on trout behaviour. However, there were many statistically significant effects of Lidocaine-Infiltrated trout compared with Saline-Infiltrated trout; none of the side-effects were adverse.

Accuracy of radiographic determination of the posterior femoral wall integrity in anterior cruciate ligament reconstruction.

OBJECTIVE: To evaluate the accuracy of radiographs in determining integrity of the posterior femoral cortex following ACL reconstruction. METHODS: Fifty adult volunteers undergoing primary arthroscopic transtibial ACL reconstructions were prospectively enrolled into this study. Plain radiographs and fine-cut CT of the operative knee were obtained post-operatively. Three blinded orthopaedic surgeons were asked to measure the distance from the femoral tunnel to the posterior cortex on lateral radiographs. Inter/intra-observer reliabilities were assessed with the interclass correlation coefficient. The true measurement of the posterior wall was determined on CT. For each, a measurement was made at the aperture, 5 mm, and 10 mm along the tunnel. Plain radiographic measurements were compared to the CT measurement of back wall using a paired t-test. RESULTS: All measurements made on the lateral radiograph were significantly different from those from the respective CT scans for each surgeon (p < 0.0001) at all points. When radiographic measurements were compared to CT at the level of the intra-articular aperture, 29 subjects showed violation of the posterior cortex, with only one being identified on plain films. At 5 mm, 7 subjects demonstrated posterior cortical violation, and none were identified on lateral radiographs. The posterior cortex remained intact in all cases at 10 mm. CONCLUSION: Lateral radiographs of the knee are insufficient for evaluation of the posterior cortical integrity following primary ACL reconstruction. Direct visualization of the femoral tunnel remains the gold standard for evaluation of the posterior wall and may be supplemented by CT scan if there remains concern over graft fixation.

What Leads to Lead: Results of a Nationwide Survey Exploring Attitudes and Practices of Orthopaedic Surgery Residents Regarding Radiation Safety.

BACKGROUND: Excessive radiation to health-care providers has been linked to risks of cancer and cataracts, but its negative effects can be substantially reduced by lead aprons, thyroid shields, and leaded glasses. Hospitals are required to provide education and proper personal protective equipment, yet discrepancies exist between recommendations and compliance. This article presents the results of a survey of U.S. orthopaedic surgery residents concerning attitudes toward radiation exposure and personal protective equipment behavior. METHODS: An invitation to participate in a web-based, anonymous survey was distributed to 46 U.S. allopathic orthopaedic surgery residency programs (1,207 potential resident respondents). The survey was conceptually divided into the following areas: demographic characteristics, training and attitudes concerning occupational hazards, personal protective equipment provision and use, and general safety knowledge. Prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated for the association between these characteristics and compliance with thyroid shield or lead gown wear. RESULTS: In this study, 518 surveys were received, with 1 survey excluded because of insufficient response, leaving 517 surveys for analysis (42.8% response rate). Ninety-eight percent of residents believed that personal protective equipment should be provided by the hospital or residency program. However, provision of personal protective equipment was not universal, with 33.8% reporting none and 54.2% reporting provision of a gown and thyroid shield. The prevalence of leaded glasses usage was 21%. Poor lead gown compliance and thyroid shield wear were associated with difficulty finding the corresponding equipment: PR, 2.51 (95% CI, 1.75 to 3.62; p < 0.001) for poor lead gown compliance and PR, 2.14 (95% CI, 1.46 to 3.16; p < 0.0001) for poor thyroid shield wear. Not being provided with personal protective equipment was also significantly associated with low compliance with both lead gowns (PR, 1.47 [95% CI, 1.04 to 2.08]; p = 0.03) and thyroid shields (PR, 1.69 [95% CI, 1.18 to 2.41]; p = 0.004). Respondents from the Southeast, West, or Midwest had lower compliance with lead gown usage. Forgetting was the number 1 reason to not wear a lead apron (42%). CONCLUSIONS: Radiation exposure is associated with increased risk of serious health problems. Our findings identified that the availability of lead personal protective equipment leads to increased compliance among residents surveyed. In addition to yearly occupational hazard training specific to orthopaedic surgery, greater efforts by residency programs and hospitals are needed to improve access to lead personal protective equipment and compliance for orthopaedic residents.

Occlusion training: pilot study for postoperative lower extremity rehabilitation following primary total knee arthroplasty.

With continued emphasis on the value of healthcare, factors such as quality of life and patient reported outcomes are critical in evaluating high-demand procedures such as knee replacement surgery. Equally important to the surgery itself is maximizing the effectiveness and efficiency of the treatment, both preoperatively and postoperatively, which can have a significant effect the final outcome. Technical outcomes of total knee replacement are generally considered excellent; however, many patients continue to have postoperative pain, functional limitations, and low treatment satisfaction. The recovery process can be difficult and is often prolonged in older patient populations. Blood flow restriction (BFR) training is a resistance exercise performed with a venous tourniquet that stimulates local changes in muscle at low resistance. Herein we report on 3 patients who participated in BFR exercises as an adjunct to their normal physical therapy following total knee arthroplasty.

Multimedia Campaign Enhances Orthopaedic Patient Perceptions of Health Care Quality: A Prospective Analysis of Effect at a Military Treatment Facility.

BACKGROUND: The importance of patient satisfaction as a measure of quality has grown with initiatives intended to enhance demand for services, refocus reimbursement paradigms, encourage health care efficiencies, and ultimately improve clinical outcomes. The purpose of our performance improvement project was to (1) characterize the effect of a two-pronged multimedia initiative on patient perceptions of health care quality and satisfaction as assessed by the Army Provider Level Satisfaction Survey (APLSS) and (2) assess for differences in APLSS scores between the surgeons that did and did not participate in the program. METHODS: Baseline APLSS data for our Department of Orthopaedic Surgery were collected and subsequently compared to APLSS results 3 months after the implementation of a department-wide multimedia campaign. The multimedia initiative consisted of two concurrently implemented interventions to the orthopaedic surgery outpatient clinics. One intervention involved placing large-framed posters about the orthopaedic clinic waiting areas on which were written, "We helped write the book," and included pictures of various orthopaedic textbooks of which attending surgeons and/or residents had contributed to as authors. The other intervention provided patients with surgeon "face sheets" upon arrival to their clinic appointments. These sheets included a picture of their attending surgeon, contact information for the surgeon's nurse care coordinator, and a brief biographical sketch of the surgeon's training, clinical interests and expertise, and other information at each surgeon's discretion. FINDINGS: Among APLSS survey results for the orthopaedic surgery clinic including all surgeons, significant increases were observed between baseline data and 3-month data for Top 1 and Top 2 responses to the questions, "How satisfied do you feel about your visit?" and "Did your surgeon listen to you carefully about your concerns and questions?" (p = 0.003 and p = 0.004, respectively). IMPACT: The implementation of a multimedia campaign resulted in significant improvements among indices of orthopaedic patient satisfaction. We believe this model could be used at other military or nonmilitary treatment facilities as a means to engender patients' familiarity with their surgeon and prompt an appreciation for his/her expertise and enhance overall patient perceptions of department-wide health care quality.

Ror2-mediated alternative Wnt signaling regulates cell fate and adhesion during mammary tumor progression.

Cellular heterogeneity is a common feature in breast cancer, yet an understanding of the coexistence and regulation of various tumor cell subpopulations remains a significant challenge in cancer biology. In the current study, we approached tumor cell heterogeneity from the perspective of Wnt pathway biology to address how different modes of Wnt signaling shape the behaviors of diverse cell populations within a heterogeneous tumor landscape. Using a syngeneic TP53-null mouse model of breast cancer, we identified distinctions in the topology of canonical Wnt ß-catenin-dependent signaling activity and non-canonical ß-catenin-independent Ror2-mediated Wnt signaling across subtypes and within tumor cell subpopulations in vivo. We further discovered an antagonistic role for Ror2 in regulating canonical Wnt/ß-catenin activity in vivo, where lentiviral shRNA depletion of Ror2 expression augmented canonical Wnt/ß-catenin signaling activity across multiple basal-like models. Depletion of Ror2 expression yielded distinct phenotypic outcomes and divergent alterations in gene expression programs among different tumors, despite all sharing basal-like features. Notably, we uncovered cell state plasticity and adhesion dynamics regulated by Ror2, which influenced Ras Homology Family Member A (RhoA) and Rho-Associated Coiled-Coil Kinase 1 (ROCK1) activity downstream of Dishevelled-2 (Dvl2). Collectively, these studies illustrate the integration and collaboration of Wnt pathways in basal-like breast cancer, where Ror2 provides a spatiotemporal function to regulate the balance of Wnt signaling and cellular heterogeneity during tumor progression.

Liposomal bupivacaine in total hip arthroplasty: Do the results justify the cost?

INTRODUCTION: Liposomal bupivacaine has a paucity of data regarding narcotic requirements and hospital length of stay in comparison to other peri-articular injections, specifically in the total hip arthroplasty (THA) population. METHODS: 69 patients who underwent THA by a single surgeon were divided into two cohorts over a 3 year period in this retrospective study comparing narcotic requirements, hospital length of stay and cost. The study group (n = 29) received liposomal bupivacaine whereas a matched control group (n = 40) received a pharmacy-mixed cocktail in peri-articular structures. Statistical and clinical differences were reported in this unfunded study. RESULTS: No difference was found in hospital length of stay [2.9 days in the study group (range 1-14) versus 3.1 days (range 1-11) in the control group, p = 0.101], however, the study group required less narcotics per day [22.6 mg (range 5-53.3) versus 29 mg (range 6.7-80.8) in the control group, p = 0.045]. The clinical difference between cohorts averaged less than one pill per day of hospitalization. The cost per patient of the local injection was more than 11 times greater in the liposomal bupivacaine group. CONCLUSION: Liposomal bupivacaine demonstrated a statistical improvement in narcotic requirements but not in hospital length of stay in comparison to a control group. The effects of liposomal bupivacaine on narcotic requirements and hospital length of stay may not justify its use in total hip arthroplasty patients given the substantial cost of these injections and the minimal clinical difference in outcomes compared to a more cost-effective injection.

ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.

Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.

Multiplatform-based molecular subtypes of non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) demonstrates remarkable molecular diversity. With the completion of The Cancer Genome Atlas (TCGA), there is opportunity for systematic analyses of the entire TCGA NSCLC cohort, including comparisons and contrasts between different disease subsets. On the basis of multidimensional and comprehensive molecular characterization (including DNA methylation and copy, and RNA and protein expression), 1023 NSCLC cases-519 from TCGA adenocarcinoma (AD) project and 504 from TCGA squamous cell carcinoma (SQCC) project-were classified using a 'cluster-of-clusters' analytic approach. Patterns from TCGA NSCLC subsets were examined in independent external databases, including the PROSPECT (Profiling of Resistance patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax) NSCLC data set. Nine genomic subtypes of NSCLC were identified, three within SQCC and six within AD. SQCC subtypes were associated with transcriptional targets of SOX2 or p63. One predominately AD subtype (with a large proportion of SQCC) shared molecular features with neuroendocrine tumors. Two AD subtypes manifested a CpG island methylator phenotype. Three AD subtypes showed high p38 and mTOR pathway activation. AD subtypes associated with low differentiation showed relatively worse prognosis. SQCC subtypes and two of the AD subtypes expressed cancer testis antigen genes, whereas three AD subtypes expressed several immune checkpoint genes including PDL1 and PDL2, corresponding with patterns of greater immune cell infiltration. Subtype associations for several immune-related markers-including PD1, PDL1, CD3 and CD8-were confirmed in the PROSPECT cohort using immunohistochemistry. NSCLC molecular subtypes have therapeutic implications and lend support to a personalized approach to NSCLC management based on molecular characterization.

5α-Androstane-3α,17ß-Diol Inhibits Neurotoxicity in SH-SY5Y Human Neuroblastoma Cells and Mouse Primary Cortical Neurons.

Low free T levels in men are associated with age-related cognitive decline and increased risk for neurotoxicity, resulting in disease. The mechanisms underlying these observations remain poorly defined. Although rapid, androgen receptor-dependent activation of ERK has been postulated as a neurotrophic and neuroprotective mechanism, actions of T metabolites such as 5α-androstane-3α,17ß-diol (3α-diol) may also be involved. We investigated the influence of 3α-diol on the induction of ERK phosphorylation in SH-SY5Y human female neuroblastoma cells and primary cortical neurons from male and female mice. In SH-SY5Y cells, ERK phosphorylation was induced by 10 nM DHT, epidermal growth factor, hydrogen peroxide (H2O2), and acetylcholine. The addition of 10 nM 3α-diol, which did not itself activate ERK, significantly inhibited ERK phosphorylation induced by DHT, epidermal growth factor, or H2O2, but not acetylcholine. In both SH-SY5Y cells and primary cortical neurons, prolonged ERK phosphorylation and caspase-3 cleavage resulting from amyloid ß-peptide 1-42 (Aß42) exposure were inhibited by cotreatment with 3α-diol. 3α-diol also reduced the loss in cellular viability induced by Aß42 or H2O2 in SH-SY5Y cells. These data suggest that T-mediated neuroprotection may occur via two distinct but complementary mechanisms: an initial rapid activation of ERK phosphorylation, followed by modulation via 3α-diol of the potentially adverse consequences of prolonged ERK activation.

Dismounted Blast Injuries in Patients Treated at a Role 3 Military Hospital in Afghanistan: Patterns of Injury and Mortality.

BACKGROUND: The purposes of this study are to define the pattern of injuries sustained by dismounted troops exposed to improvised explosive devices blasts treated at a Role 3 combat support hospital and to assess injury patterns and mortality associated with the mechanism. Our hypothesis was that mortality is associated with pelvic fracture, massive transfusion, high Injury Severity Score (ISS), multiple limb amputations, and transfer from a Role 2 facility. STUDY DESIGN: Retrospective study of 457 patients. Analysis performed on trauma registry data and systematic review of radiographs. RESULTS: 99.9% were men with a median age of 23 years and median ISS 10. 141 patients (30.9%) required massive blood transfusion. Limb amputations were frequently observed injuries, 109 of 172 amputees (63.4%) had a double amputation. 34 subjects (7.4%) had pelvic fractures; majority of pelvic fractures (88%) were unstable (Tile B or C). Risk factors associated with the overall mortality rate of 1.8% were an ISS greater than 15 (odds ratio: 11.5; 95% confidence interval: 1.38, 533; p = 0.009), need for massive transfusion (p < 0.0001), and the presence of a pelvic fracture (odds ratio: 7.63; 95% confidence interval: 1.13, 41.3; p = 0.018). CONCLUSIONS: Dismounted improvised explosive devices blast injuries result in devastating multiple limb amputations and unstable pelvic fractures, which are associated with mortality after initial trauma resuscitation at a Role 3 hospital.

International cancer seminars: a focus on kidney cancer.

Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.

Ten-Eleven Translocation Genes are Downregulated in Endometriosis.

Our previous whole genome expression analysis of endometriomas suggested dysregulation of the ten-eleven translocation genes (TET1, TET2, and TET3), involved in converting 5- methylcytosine to 5-hydroxymethylcytosine (5-hmC). The objective of this study was to validate the expression of TET genes in ectopic and eutopic endometrium and in primary cultures of human endometrial stromal fibroblasts (HESF) during in vitro decidualization and to quantify 5-hmC levels in patients with endometriosis. Blood, eutopic endometrium, and endometriotic tissues were collected at time of gynecologic surgery. HESF cultures were created from eutopic endometrium of women without (HESF-CONTROL) and with endometriosis (HESF-ENDO) and underwent in vitro decidualization. Genomic DNA from blood and tissues underwent quantification of the absolute amount of 5-hmC using ELISA. The expression of TET1, TET2, and TET3 was decreased in endometriosis compared to non-endometriosis control eutopic endometrium. Surprisingly, the global amount of 5-hmC was higher in ectopic endometrium than control eutopic endometrium, while genomic DNA from blood of women with endometriosis contained statistically significantly less 5-hmC than women without endometriosis. Expression of TET1, TET2, and TET3 was decreased in non-decidualized HESFENDO. Upon in vitro decidualization, control HESF showed decreased expression of TET3, while decidualized HESF-ENDO showed no statistically significant change in expression of TET1, TET2, or TET3. These results indicate that the TET genes are downregulated in ectopic endometrium and in HESF-ENDO, and suggest for the first time that TET genes play a role in endometriosis. High global amounts of 5-hmC in endometriotic tissues suggest unique epigenetic regulation in these tissues.