Off-label: The results of adjunctive bone morphogenetic protein for challenging femur fractures; a review of two cases.

Background: Although bone morphogenetic proteins (BMPs) are used as an adjunct to promote healing, they may have unintended effects such as heterotopic ossification (HO). The literature is limited regarding the effect of using off-label BMPs for femur fractures. Case presentation: We report two outcomes after off-label use of BMPs for the treatment of femur fractures and propose a possible explanation for the difference. Conclusions: BMPs are critical osteoinductive factors in injured bone and muscle that facilitate bony healing. However, it may be important to recognize the potentially negative effects of adding BMP to bone graft material in certain cases to stimulate bone repair. We hope this case series helps surgeons consider the risks and benefits of using BMP for femur fractures, and therefore to decide with caution when BMP is indicated.

Procedure coding in the American Joint Replacement Registry.

In October 2015, the Centers for Medicare & Medicaid Services transitioned from the 9th version of the International Classification of Diseases (ICD-9) codes for reporting patient diagnosis and medical procedures to the 10th version (ICD-10). The multitude of coding options for total joint arthroplasty in ICD-10-procedural coding (ICD-10-PCS) poses some challenges for the American Joint Replacement Registry (AJRR) in identifying precise procedures being reported. While AJRR participating hospitals are familiar with ICD-10-PCS, this new coding may not have been introduced to most AJRR participating surgeons. To address these issues, AJRR initiated an ICD-10 workgroup to define and map appropriate ICD-10 codes to total joint procedure types. This initiative sought to improve accuracy of AJRR data.

Effect of rotational prosthetic alignment variation on tibiofemoral contact pressure distribution and joint kinematics in total knee replacement.

In total knee replacement surgery, implant alignment is one of the most important criteria for successful long-term clinical outcome. During total knee replacement implantation, femoral and tibial alignment are determined through appropriate bone resections, which could vary based on patient anatomy, implant design and surgical technique and further influence loading conditions and clinical outcomes. The current research focused on three critical alignment parameters for total knee replacement insertion: femoral component internal/external (I/E) rotation, varus-valgus tibiofemoral angulation and posterior tibial slope. A computational finite element model of total knee replacement implant was developed and validated comparing with kinematic outputs generated from experimentally simulated knee joint motion. The FE model was then used to assess 12 different alignment scenarios based on previous case reports. Postoperative knee kinematics and joint contact pressure during simulated gait motion were assessed. According to the parametric study, FE model cases with femoral rotation revealed extra tibial I/E rotation in the predefined direction but negligible change in tibial anterior-posterior translation; cases with increased tibial slope showed notably increased tibial external rotation and anterior translation; cases with varus tibiofemoral angle presented slightly more tibial external rotation, whereas cases with valgus angle presented an observable increase in tibial internal rotation at the middle phase of the gait cycle. Finally, the response surface obtained from the postprocessing study demonstrated good statistical correlation with existing case study results, providing reliable estimation of peak tibiofemoral contact pressure affected by combinations of alignment parameters. The observations indicate that femoral external alignment should be favored clinically for enhanced patellar tracking and reduced contact pressure concentration for better long-term performance. Posterior tibial slope enables deep knee flexion. Extra femoral internal rotation as well as tibiofemoral varus-valgus alignment could be avoided in surgery due to deficiency in patellar tracking and high pressure concentration.

A risk assessment example for soil invertebrates using spatially explicit agent-based models.

Current risk assessment methods for measuring the toxicity of plant protection products (PPPs) on soil invertebrates use standardized laboratory conditions to determine acute effects on mortality and sublethal effects on reproduction. If an unacceptable risk is identified at the lower tier, population-level effects are assessed using semifield and field trials at a higher tier because modeling methods for extrapolating available lower-tier information to population effects have not yet been implemented. Field trials are expensive, time consuming, and cannot be applied to variable landscape scenarios. Mechanistic modeling of the toxicological effects of PPPs on individuals and their responses combined with simulation of population-level response shows great potential in fulfilling such a need, aiding ecologically informed extrapolation. Here, we introduce and demonstrate the potential of 2 population models for ubiquitous soil invertebrates (collembolans and earthworms) as refinement options in current risk assessment. Both are spatially explicit agent-based models (ABMs), incorporating individual and landscape variability. The models were used to provide refined risk assessments for different application scenarios of a hypothetical pesticide applied to potato crops (full-field spray onto the soil surface [termed "overall"], in-furrow, and soil-incorporated pesticide applications). In the refined risk assessment, the population models suggest that soil invertebrate populations would likely recover within 1 year after pesticide application, regardless of application method. The population modeling for both soil organisms also illustrated that a lower predicted average environmental concentration in soil (PECsoil) could potentially lead to greater effects at the population level, depending on the spatial heterogeneity of the pesticide and the behavior of the soil organisms. Population-level effects of spatial-temporal variations in exposure were elucidated in the refined risk assessment, using ABMs and population-level endpoints while yielding outputs that directly address the protection goals. We recommend choosing model outputs that are closely related to specific protection goals, using available toxicity data and accepted fate models to the extent possible in parameterizing models to minimize additional data needs and testing, evaluating, and documenting models following recent guidance.

Help, my rating looks bad! Coding comorbidities in arthroplasty.

In medicine today, there is a trend toward increasing transparency. Higher quality and better value are being sought, and one of the methods being used is publicly reported health care outcomes. However, there is a problem that comes from our loss of anonymity. Physicians who are being individually watched have to choose between doing what is best for the patient and doing what would look good when it is publicly reported. Often this might mean choosing not to treat a particularly sick patient who is unlikely to have a good outcome. Adjusting outcomes to account for risk factors should be a way to prevent this effect, but these methods need to be studied more. The current performance measures being released are based on administrative claims data, and to date, much of that information is not properly risk adjusted. To ensure that the increasing transparency reveals an accurate picture, it is critical that the complexity of care provided by surgeons be carefully documented. Therefore, we propose accurate coding of patients' comorbidities during hospitalization for total knee arthroplasty and total hip arthroplasty, and we have included a chart detailing our recommendations of the specific diagnostic codes that are most important.

MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes.

OBJECTIVE: Aberrant posttranscriptional regulation of matrix metalloproteinases (MMPs) by microRNA has emerged as an important factor in human diseases. The aim of this study was to determine whether the expression of MMP-13 in human osteoarthritis (OA) chondrocytes is regulated by microRNA. METHODS: Chondrocytes were stimulated with interleukin-1beta (IL-1beta) in vitro. Total RNA was prepared using TRIzol reagent. Polymerase chain reaction (PCR)-based arrays were used to determine the expression profile of 352 human microRNA. Gene expression was quantified using TaqMan assays, and microRNA targets were identified using bioinformatics. Transfection with reporter construct and microRNA mimic was used to verify suppression of target messenger RNA (mRNA). Gene expression of argonaute and Dicer was determined by reverse transcription-PCR, and expression of protein was determined by immunoblotting. The role of activated MAP kinases (MAPKs) and NF-kappaB was evaluated using specific inhibitors. RESULTS: In IL-1beta-stimulated OA chondrocytes, 42 microRNA were down-regulated, 2 microRNA were up-regulated, and the expression of 308 microRNA remained unchanged. In silico analysis identified a sequence in the 3'-untranslated region (3'-UTR) of MMP-13 mRNA complementary to the seed sequence of microRNA-27b (miR-27b). Increased expression of MMP-13 correlated with down-regulation of miR-27b. Overexpression of miR-27b suppressed the activity of a reporter construct containing the 3'-UTR of human MMP-13 mRNA and inhibited the IL-1beta-induced expression of MMP-13 protein in chondrocytes. NF-kappaB and MAPK activation down-regulated the expression of miR-27b. CONCLUSION: Our data demonstrated the expression of miR-27b in both normal and OA chondrocytes. Furthermore, IL-1beta-induced activation of signal transduction pathways associated with the expression of MMP-13 down-regulated the expression of miR-27b. Thus, miR-27b may play a role in regulating the expression of MMP-13 in human chondrocytes.

Green tea polyphenol epigallocatechin-3-gallate inhibits advanced glycation end product-induced expression of tumor necrosis factor-alpha and matrix metalloproteinase-13 in human chondrocytes.

INTRODUCTION: The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age-related accumulation of advanced glycation end products (AGEs) can activate chondrocytes and induce the production of proinflammatory cytokines and matrix metalloproteinases (MMPs). In the present study, we examined the effect of epigallocatechin-3-gallate (EGCG) on AGE-modified-BSA (AGE-BSA)-induced activation and production of TNFalpha and MMP-13 in human OA chondrocytes. METHODS: Human chondrocytes were derived from OA cartilage by enzymatic digestion and stimulated with in vitro-generated AGE-BSA. Gene expression of TNFalpha and MMP-13 was measured by quantitative RT-PCR. TNFalpha protein in culture medium was determined using cytokine-specific ELISA. Western immunoblotting was used to analyze the MMP-13 production in the culture medium, phosphorylation of mitogen-activated protein kinases (MAPKs), and the activation of NF-kappaB. DNA binding activity of NF-kappaB p65 was determined using a highly sensitive and specific ELISA. IkappaB kinase (IKK) activity was determined using an in vitro kinase activity assay. MMP-13 activity in the culture medium was assayed by gelatin zymography. RESULTS: EGCG significantly decreased AGE-stimulated gene expression and production of TNFalpha and MMP-13 in human chondrocytes. The inhibitory effect of EGCG on the AGE-BSA-induced expression of TNFalpha and MMP-13 was mediated at least in part via suppression of p38-MAPK and JNK activation. In addition, EGCG inhibited the phosphorylating activity of IKKbeta kinase in an in vitro activity assay and EGCG inhibited the AGE-mediated activation and DNA binding activity of NF-kappaB by suppressing the degradation of its inhibitory protein IkappaBalpha in the cytoplasm. CONCLUSIONS: These novel pharmacological actions of EGCG on AGE-BSA-stimulated human OA chondrocytes provide new suggestions that EGCG or EGCG-derived compounds may inhibit cartilage degradation by suppressing AGE-mediated activation and the catabolic response in human chondrocytes.

Evaluation of intra-annual variation in U.S. Geological Survey National Water Quality Assessment ground water quality data.

Assessment of ground-water quality trends under the U.S. Geological Survey National Water-Quality Assessment Program (NAWQA) included the analysis of samples collected on a quarterly basis for 1 yr between 2001 and 2005. The purpose of this quarterly sampling was to test the hypothesis that variations in the concentration of water-quality parameters of selected individual wells could demonstrate that the intra-annual variation was greater or less than the decadal changes observed for a trend network. Evaluation of more than 100 wells over this period indicates that 1 yr of quarterly sampling is not adequate to address the issue of intra-annual variation because variations seem to be random and highly variable between different wells in the same networks and among networks located in different geographical areas of the USA. In addition, the data from only 1 yr makes it impossible to assess whether variations are due to univariate changes caused by land use changes, hydrologic variations due to variable recharge, or variations caused by ground-water pumping. These data indicate that funds allocated to this activity can be directed to the collection of more effective trend data, including age dating of all wells in the NAWQA network using multiple techniques. Continued evaluation of data and updating of monitoring plans of the NAWQA program is important for maintaining relevance to national goals and scientific objectives.

Exchange femoral nailing: a new technique for removal of a broken nail.

Exchange femoral nailing is the preferred method for treating femoral nonunions. When the index femoral nail is broken, the difficulty of exchange nailing increases dramatically. In this article, we describe a new technique for removing a broken retrograde nail--advancing it out of the proximal end of the femur.

Atrophic femoral nonunion with bone loss: treatment with monorail transport: a case report.

Nonunions are an uncommon outcome of femoral fractures. Atrophic nonunions with a leg length discrepancy secondary to bone loss are often the most difficult to treat, and the treatment options are limited. We present a case that uses concomitant monolateral external fixation and intramedullary nailing to heal a nonunion and perform a simultaneous 7-cm lengthening procedure in a 33-year-old female.