PAK1-dependent mechanotransduction enables myofibroblast nuclear adaptation and chromatin organization during fibrosis.

Myofibroblasts are responsible for scarring during fibrosis. The scar propagates mechanical signals inducing a radical transformation in myofibroblast cell state and increasing profibrotic phenotype. Here, we show mechanical stress from progressive scarring induces nuclear softening and de-repression of heterochromatin. The parallel loss of H3K9Me3 enables a permissive state for distinct chromatin accessibility and profibrotic gene regulation. Integrating chromatin accessibility profiles with RNA expression provides insight into the transcription network underlying the switch in profibrotic myofibroblast states, emphasizing mechanoadaptive regulation of PAK1 as key drivers. Through genetic manipulation in liver and lung fibrosis, loss of PAK1-dependent signaling impairs the mechanoadaptive response in vitro and dramatically improves fibrosis in vivo. Moreover, we provide human validation for mechanisms underpinning PAK1-mediated mechanotransduction in liver and lung fibrosis. Collectively, these observations provide insight into the nuclear mechanics driving the profibrotic chromatin landscape in fibrosis, highlighting actomyosin-dependent mechanisms as potential therapeutic targets in fibrosis.

Hip Resurfacing in Teenagers.

BACKGROUND: The goals of hip resurfacing are to relieve pain, restore function, and preserve future reconstructive options. Hip resurfacing is an attractive and sometimes the only option when the femoral canal is blocked, making total hip arthroplasty (THA) difficult. Hip resurfacing also can be an attractive option for a teenager on the rare occasion when a hip implant is needed. METHODS: A cementless ceramic-coated femoral resurfacing implant matched with a highly cross-linked polyethylene acetabular bearing was used in 105 patients (117 hips) aged 12 to 19 years. The mean follow-up was 14 years (range, 5 to 25). No patients were lost to follow-up before 19 years. Osteonecrosis, residuals of trauma, developmental dysplasia, and childhood hip diseases were the common reasons requiring surgery. Patients were evaluated using patient-reported outcomes, patient acceptable symptom states (PASS), and implant survivorships. Radiographs and retrievals were also examined. RESULTS: There were 2 revisions (polyethylene liner exchange at 12 years and femoral revision for osteonecrosis at 14 years). The mean postoperative Hip Disability Osteoarthritis Outcome Score (HOOS) was 94 points (range, 80 to 100) and the mean Harris Hip Score (HHS) score was 96 points (range, 80 to 100). All patients achieved Minimal Clinically Important Difference improvement in their HHS and HOOS scores. There were 99 (85%) hip resurfacing procedures achieving a satisfactory PASS and 72 (69%) patients were active in sports. CONCLUSION: Hip resurfacing is a highly technical procedure. Careful implant selection is required. The meticulous preoperative planning, careful extensile surgical exposure, and exacting implant placement in this study likely contributed to the favorable results achieved. Hip resurfacing allows THA as a future option in patients where the lifetime revision rate is a major consideration.

Circadian Disruption Primes Myofibroblasts for Accelerated Activation as a Mechanism Underpinning Fibrotic Progression in Non-Alcoholic Fatty Liver Disease.

Circadian rhythm governs many aspects of liver physiology and its disruption exacerbates chronic disease. CLOCKΔ19 mice disrupted circadian rhythm and spontaneously developed obesity and metabolic syndrome, a phenotype that parallels the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD represents an increasing health burden with an estimated incidence of around 25% and is associated with an increased risk of progression towards inflammation, fibrosis and carcinomas. Excessive extracellular matrix deposition (fibrosis) is the key driver of chronic disease progression. However, little attention was paid to the impact of disrupted circadian rhythm in hepatic stellate cells (HSCs) which are the primary mediator of fibrotic ECM deposition. Here, we showed in vitro and in vivo that liver fibrosis is significantly increased when circadian rhythm is disrupted by CLOCK mutation. Quiescent HSCs from CLOCKΔ19 mice showed higher expression of RhoGDI pathway components and accelerated activation. Genes altered in this primed CLOCKΔ19 qHSC state may provide biomarkers for early liver disease detection, and include AOC3, which correlated with disease severity in patient serum samples. Integration of CLOCKΔ19 microarray data with ATAC-seq data from WT qHSCs suggested a potential CLOCK regulome promoting a quiescent state and downregulating genes involved in cell projection assembly. CLOCKΔ19 mice showed higher baseline COL1 deposition and significantly worse fibrotic injury after CCl4 treatment. Our data demonstrate that disruption to circadian rhythm primes HSCs towards an accelerated fibrotic response which worsens liver disease.

Cementless Metal-Free Ceramic-Coated Shoulder Resurfacing.

Shoulder resurfacing is a versatile, bone-conserving procedure to treat arthritis, avascular necrosis, and rotator cuff arthropathy. Shoulder resurfacing is of interest to young patients who are concerned about implant survivorship and those in need of a high level of physical activity. Using a ceramic surface reduces wear and metal sensitivity to clinically unimportant levels. Between 1989 and 2018, 586 patients received cementless, ceramic-coated shoulder resurfacing implants for arthritis, avascular necrosis, or rotator cuff arthropathy. They were followed for a mean of 11 years and were assessed using the Simple Shoulder Test (SST) and Patient Acceptable Symptom State (PASS). CT scans were used in 51 hemiarthroplasty patients to assess the glenoid cartilage wear. Seventy-five patients had a stemmed or stemless implant in the contralateral extremity. A total of 94% of patients had excellent or good clinical results and 92% achieved PASS. 6% of patients required a revision. A total of 86% of patients preferred their shoulder resurfacing prosthesis over a stemmed or stemless shoulder replacement. The glenoid cartilage wear at a mean of 10 years was 0.6 mm by a CT scan. There were no instances of implant sensitivity. Only one implant was removed due to a deep infection. Shoulder resurfacing is an exacting procedure. It is clinically successful, with excellent long-term survivorship in young and active patients. The ceramic surface has no metal sensitivity, very low wear, and, therefore, it is successful as a hemiarthroplasty.

Disease Progression After Unicompartmental Arthroplasty: Add a Compartment or Revise to Total Knee Arthroplasty?

BACKGROUND: Five percent to 7% of unicompartmental knee arthroplasties (UKA) require revision for disease progression in untreated compartment(s), most commonly to total knee arthroplasty (TKA). TKA requires removal of bone and usually the anterior cruciate ligament. Preserving the UKA and converting to a bicompartmental arthroplasty (BCA) by performing a second UKA is an alternative. METHODS: The results of 73 UKA-BCA patients were compared to 75 patients treated by UKA-TKA revision. Knee Society, Knee Osteoarthritis Outcome Score Joint Replacement, and patient satisfaction scores were collected by a blinded therapist. Patients were asked about their implant preference and recovery. Twenty-two UKA-BCA revision patients had a UKA (6) or TKA (16) in the contralateral knee; thus, a direct comparison of UKA-BCA to both UKA and TKA was possible. RESULTS: Of the UKA-BCA patients, 69 (94%) had excellent or good, 2 (3%) fair, and 2 (3%) poor outcomes with 1 patient requiring revision to TKA. Of patients with a TKA in the contralateral knee, 13 (81%) preferred the UKA-BCA replacement and 3 (19%) preferred the TKA. All patients said the UKA-BCA revision recovery was similar or easier than their initial UKA. Of UKA-TKA revisions, 59 (79%) had excellent or good, 9 (12%) fair, and 7 (9%) poor outcomes. There was 1 wound infection and 1 re-revision in the UKA-BCA group and 1 wound infection and 3 re-revisions in the UKA-TKA group. The Knee Osteoarthritis Outcome Score Joint Replacement and Knee Society Scores were better for UKA-BCA compared to UKA-TKA. CONCLUSION: UKA-BCA is a successful treatment for disease progression following UKA.

Optimizing Readability and Format of Plain Language Summaries for Medical Research Articles: Cross-sectional Survey Study.

BACKGROUND: Plain language summaries (PLSs) are intended to provide readers with a clear, nontechnical, and easily understandable overview of medical and scientific literature; however, audience preferences for specific PLS formats have yet to be fully explored. OBJECTIVE: This study aims to evaluate the preferred readability level and format for PLSs of medical research articles of different disease states via a web-based survey of audiences of different age groups. METHODS: Articles describing phase III clinical trials published in top-level, peer-reviewed journals between May 2016 and May 2018 were identified for 3 chronic disease states representing a range of adult patient age groups: (1) psoriasis, a skin disease representative of younger patients; (2) multiple sclerosis (MS), a neurological disease representative of middle-aged patients; and (3) rheumatoid arthritis (RA), a painful joint disease representative of older patients. Four PLSs were developed for each research article, of which 3 were text-only summaries (written with high, medium, and low complexity) and 1 was an infographic. To evaluate each of the 4 PLS formats, a 20-question open survey (specific to one of the 3 diseases) was sent to a representative sample selected via UK-based patient association websites, Twitter, and Facebook patient groups. A weighted-average calculation was applied to respondents' ranked preferences for each PLS format. RESULTS: For all 3 articles, the weighted-average preference scores showed that infographic (psoriasis 2.91, MS 2.71, and RA 2.78) and medium-complexity text-based PLS (reading age 14-17 years, US Grade 9-11; psoriasis 2.90; MS 2.47; RA 2.77) were the two most preferred PLS formats. CONCLUSIONS: Audience preferences should be accounted for when preparing PLSs to accompany peer-reviewed original research articles. Oversimplified text can be viewed negatively, and graphical summaries or medium-complexity text-based summaries appear to be the most popular. PLAIN LANGUAGE SUMMARY: Patients and caregivers should have the chance to read about medical research in a format they can understand. However, we do not know much about the formats that people with different illnesses or ages prefer. Researchers wanted to find out more about this. They selected 3 medical articles about illnesses that affect different age groups: psoriasis (younger patients), multiple sclerosis (middle-aged patients), and rheumatoid arthritis (older patients). They created 4 summaries of each article. One was a graphical summary, and the other 3 were words-only summaries of high, medium, and low complexity. Then, the researchers posted surveys on UK patient group websites and Facebook patient groups to ask people what they thought of the summaries. The surveys were taken by 167 people. These people were patients with psoriasis, multiple sclerosis, or rheumatoid arthritis, or their caregivers. Most were women, and about half had a university degree. For each illness, most people preferred the graphical summary. Among the word-only summaries, most people preferred the medium-complexity wording written for a reading age of 14 to 17 years. People felt that the graphical and medium-complexity summaries were clear and concise, while the others used jargon or were too simple. Authors of medical articles should remember these results when writing summaries for patients. More research is needed about the preferences of other people, such as those with other illnesses. (See Multimedia Appendix 1 for the graphical summary of the plain language summary.).

Wear and performance of a tripolar total hip replacement.

Background: An unconstrained tripolar hip replacement matches a large capacity two-piece metal/polyethylene acetabular component with a bipolar prosthesis. This combination of accepted technology is different than the relatively new dual mobility prosthesis. The goal is to protect against dislocation and allow close to a normal range of motion (ROM). So far there has not been enough information about wear and performance of tripolar hip replacement to support its wide use. Methods: Twenty-four tripolar prostheses were retrieved from 23 patients after a mean of 14 years (range, 5-21 years). All implants had been placed in high-demand patients who participated in adventure sports, had occupations where a dislocation would be dangerous, or in patients undergoing revision. The tripolar prosthesis has three important design features: (I) the acetabular component uses highly cross-linked polyethylene with an internal diameter of 41-54 mm, (II) the bipolar is titanium nitride-coated, and (III) the bipolar prosthesis has positive eccentricity. The retrievals were evaluated for wear, performance, and mechanical function. Results: The total volumetric wear was 24 mm3/yr. compared to 54 mm3/yr. For a dual mobility prosthesis and 38 mm3/yr. for a 40 mm conventional hip replacement. The jump distance was 16 mm compared to 12 mm for a 36 mm hip replacement. There was no osteolysis. The combined flexion/extension was 145 compared to 119 for a conventional prosthesis. The mean UCLA score was 7.9. Radiographs showed continued shared movement between the inner and outer articulations. The prosthetic bipolar separation force was 2,180 N. High-demand activities generate approximately 340 N. Conclusions: The wear of this tripolar hip prosthesis is low below the osteolytic threshold. The increased ROM and increased jump distance provide the most stable unconstrained hip replacement available. The wear and mechanical performance seen in this study suggest a lifetime of use is possible in even the highest demand patients. The absence of intraprosthetic dislocation, metal wear reaction, and limited acetabular stress shielding make this a safer technology compared to a dual mobility prosthesis.

Visible light photocatalytic bismuth oxide coatings are effective at suppressing aquatic cyanobacteria and degrading free-floating genomic DNA.

Access to safe drinking water free from microbial pollution is an issue of global concern. The use of photocatalytic thin films in water treatment has focused on titanium dioxide, which requires UV-activation, proving a potential barrier to upscaling and implementation in the real world. Visible-light-activated photocatalytic thin films, such as bismuth oxide, have recently been shown to have antimicrobial properties. However, more understanding of the photocatalytic effect on the microbial population in water is required. Glass beads coated with bismuth oxide were incubated with either Microcystis aeruginosa, Anabaena sp. or free-floating genomic DNA. The presence of bismuth oxide-coated glass beads was able to rapidly stop a population of cyanobacteria from increasing. The coated beads were also able to degrade genomic DNA. Leachate from the beads showed no increase in toxicity against human liver cells. This data demonstrates the efficacy of bismuth oxide-coated glass beads for controlling potentially dangerous cyanobacterial populations, whilst potentially reducing the amount of free-floating genomic DNA (an essential issue in the face of antimicrobial resistance) - all of which should be essential considerations in emerging water treatment technologies.

SOX9 is required for kidney fibrosis and activates NAV3 to drive renal myofibroblast function.

Renal fibrosis is a common end point for kidney injury and many chronic kidney diseases. Fibrogenesis depends on the sustained activation of myofibroblasts, which deposit the extracellular matrix that causes progressive scarring and organ failure. Here, we showed that the transcription factor SOX9 was associated with kidney fibrosis in humans and required for experimentally induced kidney fibrosis in mice. From genome-wide analysis, we identified Neuron navigator 3 (NAV3) as acting downstream of SOX9 in kidney fibrosis. NAV3 increased in abundance and colocalized with SOX9 after renal injury in mice, and both SOX9 and NAV3 were present in diseased human kidneys. In an in vitro model of renal pericyte transdifferentiation into myofibroblasts, we demonstrated that NAV3 was required for multiple aspects of fibrogenesis, including actin polymerization linked to cell migration and sustained activation of the mechanosensitive transcription factor YAP1. In summary, our work identifies a SOX9-NAV3-YAP1 axis involved in the progression of kidney fibrosis and points to NAV3 as a potential target for pharmacological intervention.

Hip Replacement or Hip Resurfacing with a Highly Cross-Linked Polyethylene Acetabular Bearing: A Qualitative and Quantitative Preference Study.

BACKGROUND: Most surgeons strongly prefer total hip arthroplasty (THA) over hip resurfacing arthroplasty (HRA). However, it is unknown whether patients prefer the results of 1 procedure over the other. The purpose of this study was to answer 3 questions: (1) Do patients with an HRA on 1 side and a THA on the other notice a difference? (2) Do patients have a preference? (3) What are the reasons for their preference? METHODS: Between 1998 and 2012, 332 patients underwent staged bilateral hip arthroplasties with cementless THA on 1 side and HRA on the other, with a highly cross-linked polyethylene acetabular component used for both. Patient preferences, Harris hip scores, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were recorded by blinded examiners. Patients provided reasons for their preference in semi-structured interviews using both quantitative and qualitative measures. RESULTS: The mean follow-up was 11 years (range, 7 to 21 years). Of 324 patients with complete data, 279 (86%) preferred the HRA, 19 (6%) preferred the THA, and 26 (8%) had no preference. The most common reasons for preference for the HRA were better balance (n = 143), felt more normal (n = 141), better activity participation/more reliable hip during sports (n = 139), and stronger on stairs (n = 129). A fair or poor outcome was reported by the patient after 4 HRAs and 7 THAs. The remainder of the patients reported improved function and satisfactory pain relief and range of motion for both hips. CONCLUSIONS: In conclusion, most patients in this study preferred the side on which the HRA had been done. Since essentially all current hip prostheses perform well, a paired bilateral study may be the optimal way to determine patient preferences and values of HRA compared with THA. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Decision Matrix-Guided Treatment of Infected Hip Resurfacing.

Infection can nullify the benefits of a successful hip resurfacing arthroplasty (HRA). Even with infection, it may be feasible to meet a patient's desire to retain the implant. The author reviewed records of 301 patients with infected hip resurfacing. Patients expressed their treatment preference using a decision matrix that considered treatment efficacy, consequences of treatment failure, probability of infection worsening, and treatment side effects. Patient interviews were analyzed to determine their experience with treatment. Treatment alternatives were (1) no surgery, oral antibiotics, and local incision care; (2) surgical debridement, IV antibiotics, and implant retention; (3) one-stage explantation, IV antibiotics, and reimplantation generally with conversion to total hip replacement; and (4) two-stage reimplantation with conversion to total hip replacement. Mean follow-up was 9 years (range, 2-34). Pretreatment qualitative themes found that some patients believed their early infection symptoms were not validated, leading to diagnostic delays. During treatment, themes centered on mobility and lifestyle limitations for those receiving revision surgery. Posttreatment themes were reduced function following revision compared to pretreatment function. Of the 301 patients, 199 (66%) had nonoperative care, with remission for 169 (85%); 40 (13%) had one-stage reimplantation and 36 (90%) had infection remission; 16 (5%) had two-stage reimplantation with remission in 14 (87%); and 46 (16%) had debridement and implant retention, with remission for 38 (83%). The matrix showed that patients with infected HRA preferred nonoperative care, which was successful for 85%. Qualitative themes found less patient distress with nonoperative treatment and the greatest patient distress with two-stage revision.

Total Articular Knee Replacement Using Polyurethane.

This study reviewed the early use of polyurethane for total knee resurfacing, the long-term results of polycarbonate urethane (PCU) for total knee replacement and conducted wear simulator testing of PCU. In 1959 and 1960, 10 patients underwent total articular polyurethane knee replacement (polyethylene was not available). The polyurethane was placed on the articular surface of the femur with metal surfaces on the tibia and patella. In 1996 and 1997, four patients received a newer PCU tibial insert in revision procedures; all had well-fixed prostheses, but no revision polyethylene implants were available. In addition, this study evaluated six new PCU tibial inserts in a 10-million cycle (Mc) wear simulator. All 10 of the early knees performed well clinically and 2 knees were functional for more than 30 years. Of the four more recent patients, all knees remain functional at more than 20 years' follow-up with no signs of wear or osteolysis. Wear simulator testing found mean material loss of 14.2 mg/Mc which equates to a volumetric wear of 11.9 mg/Mc, similar to the wear of conventional polyethylene. Polyurethane performs well as conventional polyethylene but not better than current cross-linked polyethylene tibial inserts. Its large wear particles (mean, 11 µm) and biocompatibility are less likely to cause an inflammatory response leading to pain and bone loss. Newer, superior polyurethanes can again be considered a candidate material for the tibial insert of a total knee replacement. A larger study may be able to validate polyurethane as an alternative material for joint replacement.

Large Diameter Total Hip Replacement for Acute Displaced Femoral Neck Fracture.

BACKGROUND: Total hip replacement for acute femoral neck fracture is the preferred treatment for younger, physically and socially active patients. The risks, particularly dislocation, are higher than for elective total hip replacement for arthritis. Larger diameter bearings provide increased stability and can be used in this higher risk setting. METHODS: In this study, 391 patients with acute femoral neck fractures were treated with total hip replacement using 40-mm and 44-mm femoral heads. These femoral heads were placed in thin, two-piece, highly cross-linked polyethylene-lined acetabular shells. The procedures were performed by community orthopedic surgeons using the posterior approach. Patients were mobilized immediately and with only routine postoperative precautions. Patients were followed for 5 years. Follow-up radiographs were measured to determine component position. RESULTS: There were no dislocations in the first 3 years following surgery, but there were 3 late dislocations. There were 29 revisions performed for impingement (n = 8), infection (n = 12), periprosthetic fracture (n = 3), instability (n = 2), and component loosening (n = 4). No instances of polyethylene wear or trunnion corrosion were identified. Overall, 37% of acetabular components simultaneously met the safe zone targets for inclination and anteversion. The mean Harris hip score was 90. CONCLUSIONS: The dislocation rate in this study was lower than in prior studies, as was the overall revision rate. Using a femoral head ≥ 40 mm is a simple measure that reduces the dislocation rate without adding additional cost or complexity to the procedure. This device is available to all surgeons and may be an advantage to the hip surgeon treating femoral neck fractures with total hip replacement.

Deformation and Recovery of Thin Metal-Backed, Two-Piece Polyethylene Acetabular Resurfacing Components.

Acetabular underreaming is a bone preservation and fixation strategy in hip resurfacing. Prior reports of acetabular component deformation have been cadaveric studies. In this study, I sought to determine deformation of thin shells and very thin highly cross-linked polyethylene in patients, the effects of increasing underreaming and liner-head clearance, and whether deformation accelerates wear. Overall, 32 two-piece metal-backed polyethylene resurfacing acetabular components placed with 3-4 mm of underreaming were retrieved postmortem or during revision after a mean of 9 years of patient use. Shells were 54-64 mm in external diameter. The components were 2-mm-thick porous-coated shells and 4-mm highly cross-linked polyethylene liners. Deformation was measured during insertion, 30 minutes after implantation, after reducing the hip and testing range of motion, and at retrieval. Standard liner-head clearance was 0.3 mm, and clearances up to 2.8 mm were also used. Acetabular shells deformed a mean of 0.58 mm on insertion and deformed 0.23 mm at retrieval. Initial liner deformation of 0.29 mm decreased to 0.15 mm on retrieval. With liner-head clearance of 2.8 mm, the mean shell and liner deformations at retrieval were 0.36 mm and 0.29 mm, respectively. The calculated insertional force was 367 Nm. No acetabular fractures, shell or liner failures, or adverse clinical consequences were observed. Mean linear wear was 0.005 mm/yr. Thin resurfacing acetabular shells and liners deform when placed with 3-4 mm of underreaming, which lessens with loading, bone relaxation, and clinical use. Bone preservation by underreaming is beneficial during hip resurfacing surgery.

Publisher Correction: SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Zeolite-embedded silver extends antimicrobial activity of dental acrylics.

The insertion of prosthetic devices into the oral cavity affects the oral microflora and results in accumulation of microorganisms on the prosthetic surface. Such fouling of denture surfaces can lead to a number of oral diseases and consequently to the replacement of the denture. Here, we report the post-synthesis introduction of silver in zeolite-loaded dental acrylic (DAZ) resins that does not influence the mechanical or aesthetic properties of the DA resins, and provides them with a long-term antimicrobial activity. Na-FAU zeolite (2 wt%) was incorporated into DA resin, which was conventionally processed and cut into 10 mm × 20 mm × 3 mm coupons. The Na+ in the zeolite was then exchanged with Ag+ via immersion of the DAZ coupons in 0.01 M AgNO3 solution to obtain DAZ/Ag-treated coupons used in antimicrobial tests. Antimicrobial tests showed that the DAZ/Ag-treated coupons were active against Candida albicans (a reference and a clinically relevant strain), Streptococcus mutans and Fusobacterium nucleatum. Ag leaching tests on the Ag-charged coupons at 1, 2, 3, 4, 7, 14, 30 and 45 days of incubation in distilled water at 37 °C, indicated sustained release of silver. Antimicrobial tests using a reference Candida albicans strain showed that the leached coupons retained antimicrobial activity after 45 days immersion in distilled water, but, after 60 days incubation no antimicrobial activity was observed. Cytotoxicity assay results indicated that the DAZ/Ag-treated coupons showed no additional cytotoxicity compared to neat dental acrylic coupons.

SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis.

Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis and progression of liver fibrosis. Identifying core regulators of ECM deposition may lead to urgently needed diagnostic and therapetic strategies for the disease. The transcription factor Sex determining region Y box 9 (SOX9) is actively involved in scar formation and its prevalence in patients with liver fibrosis predicts progression. In this study, transcriptomic approaches of Sox9-abrogated myofibroblasts identified >30% of genes regulated by SOX9 relate to the ECM. Further scrutiny of these data identified a panel of highly expressed ECM proteins, including Osteopontin (OPN), Osteoactivin (GPNMB), Fibronectin (FN1), Osteonectin (SPARC) and Vimentin (VIM) as SOX9 targets amenable to assay in patient serum. In vivo all SOX-regulated targets were increased in human disease and mouse models of fibrosis and decreased following Sox9-loss in mice with parenchymal and biliary fibrosis. In patient serum samples, SOX9-regulated ECM proteins were altered in response to fibrosis severity, whereas comparison with established clinical biomarkers demonstrated superiority for OPN and VIM at detecting early stages of fibrosis. These data support SOX9 in the mechanisms underlying fibrosis and highlight SOX9 and its downstream targets as new measures to stratify patients with liver fibrosis.

Polyethylene Hip Resurfacing to Treat Arthritis and Severe Acetabular Insufficiency.

BACKGROUND: Hip dysplasia is the leading cause of hip arthritis in young adults. These patients often participate in active lifestyles that require a full and stable range of motion. METHODS: Between 2001 and 2011, 232 consecutive polyethylene resurfacing arthroplasties were performed in 201 patients with advanced arthritis from severe acetabular insufficiency due to dysplasia. All patients had Crowe II or III disease. Their mean age at surgery was 43 years. A 2-piece cementless acetabular resurfacing shell with dome screws and a highly cross-linked polyethylene liner were implanted to provide secure fixation, early weight bearing, and a stable hip. Additional structural bone grafts and/or fixation were not used. A cemented or cementless resurfacing prosthesis was used on the femur. RESULTS: During a mean follow-up of 10 years, 8 hips (3.5%) were converted to a total hip arthroplasty due to acetabular loosening (1), femoral neck fracture (2), femoral osteonecrosis (2), infection (2), or persistent pain (1), resulting in a mean survival of the resurfacing prostheses of 96% (95% confidence interval 89-98). There were no pending revisions and no dislocations. At 2 years postoperative, Harris Hip Scores improved from a preoperative mean of 55 to 97 and University of California Los Angeles activity scores improved from 5 to 8. CONCLUSION: Hip resurfacing using a 2-piece polyethylene acetabular component for advanced dysplasia has resulted in excellent function and implant survivorship with a low rate of complications at mid-term follow-up.

Hip resurfacing in patients with severe osteoarthritis and blocked medullary canal.

INTRODUCTION: This study evaluated the effectiveness of hip resurfacing in patients with femoral deformities or retained femoral implants. Implant removal and conversion total hip replacement (CTHR) have been associated with increased operative time, blood loss, and cost. Removing intramedullary nails in particular can be difficult and can result in a more difficult recovery and/or complications. Hip resurfacing can be performed with a blocked femoral canal and has the possible additional benefits of a less-complex procedure, improved functional outcomes, better patient survivorship, and a possibly less-complicated revision should a failure occur. MATERIALS AND METHODS: The author performed hip resurfacing in 61 patients (65 hips) with a blocked femur who had been advised elsewhere that they could not undergo THR without also undergoing additional surgical procedures. The perioperative complexity of resurfacing was evaluated by recording operative time, blood loss and functional outcomes using the Harris Hip Score (HHS) and Short-Form 12 (SF-12) questionnaire. Implant survivorship was evaluated by the need for revision surgery. RESULTS: At 9 years' mean follow-up (range 5-19 years), 59 of the 61 patients presented for postoperative evaluation. The mean operative time was 104 minutes and the mean blood loss was 300 cc. The mean HHS improved from 41 to 92 ( p < 0.001) and the mean SF-12 physical and mental scores improved from 26 to 49 and from 44 to 54, respectively ( p < 0.001). None of the procedures failed or required revision. CONCLUSION: Canal-sparing hip resurfacing is a successful and less complicated option than CTHR when there is deformity or retained implant blocking the femoral canal.