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.

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.).

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.

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.

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.

Public Perceptions About Nerve Injury From Hip Replacement Surgery.

BACKGROUND: Nerve injury is a distressing complication for patients and surgeons that is difficult and frustrating to understand and treat. Whether the standard of care has been met when this complication occurs is a common question for both patients and surgeons but there is no information about how the public feels about nerve injury. METHODS: The author surveyed 1409 individuals insured in a senior products health program using a 22-item questionnaire about nerve injury during hip replacement. Participants were given written descriptions of total hip arthroplasty, nerve injury, and the standard of care. RESULTS: Seventeen percent of participants indicated that a direct nerve laceration is a standard of care violation. Respectively, 98%, 100%, 94%, and 97% of participants responded that the standard of care requires the surgeon to promptly identify the nerve injury, completely inform the patient about the nature and prognosis of the injury, and present options for treating the nerve injury. Eleven percent indicated that they lack trust in health care. Participants with distrust were more likely to find a standard of care violation than other participants. Women and non-white participants responded more commonly that a standard of care violation occurred with the nerve injury. Income level, age, prior surgery, and educational background were not differentiating factors as to whether participants found that a violation of the standard of care had occurred. CONCLUSION: Most participants would accept the possibility of nerve injury during hip replacement but they would expect to be informed in advance that this complication is possible.

Outcome of surgery for nerve injury following total hip arthroplasty.

PURPOSE: During hip replacement, nerves in the operative field can be injured accidently. Additional surgical procedures can help restore function and reduce pain if there has been no recovery. METHODS: One-hundred sixty-two patients presented with nerve injuries, and 113 were candidates for surgical treatment. The author performed 91 procedures on the injured limb (80 patients; 11 had 2 procedures) consisting of shortening, sympathectomy, tendon transfer, neurolysis or nerve repair/graft and 30 spinal and three fibular-neck decompressions. A meaningful recovery was defined as an increase of >1 level in strength or a reduction of >2 points on the visual analogue (VAS) pain scale. RESULTS: Of 21 shortening procedures, 15 improved; of 12 nerve repair/grafting procedures, four improved. No patient >55 years of age made a meaningful recovery from a nerve repair/graft. One obturator nerve was resected and did not improve, and two were buried in muscle and had less pain. Of seven sympathectomies, six had less dysesthetic pain. Of 28 nerves treated with neurolysis, 24 made a meaningful recovery, with 13 making a near complete recovery. Of three fibular decompressions, two recovered completely. Of 20 tendon transfers, 18 made a meaningful recovery. Of 30 spinal decompressions, 25 made a meaningful recovery. There were six (5.3%) surgical complications (2 worsening pain, 2 infections, 2 deformities from tendon transfer). CONCLUSIONS: If a sciatic, femoral or obturator nerve injury due to hip replacement does not recover spontaneously, additional surgical procedures can be of benefit.

Adventure sports and sexual freedom hip replacement: the tripolar hip.

Certain athletic activities and lifestyles require a completely stable and very mobile hip. Total hip replacement with a natural femoral head size and two mobile-bearing surfaces (i.e., a "tripolar" prosthesis) is the most stable prosthesis. Elegant design and wear-resistant bearing surfaces are the keys to long-term implant survivorship. The hypothesis is that a ceramic-coated tripolar prosthesis using highly cross-linked polyethylene can provide full function and complete stability with low wear. This study sought to determine: (1) patient-reported outcomes, (2) functional outcomes, (3) implant survivorship and complications, and (4) postoperative sexual limitations. Between 1998 and 2011, the author performed 160 primary total hip replacements using tripolar prostheses in patients participating in adventure sports and other physically demanding activities. The institutional review board approved this study. The inclusion criteria were patients who needed unrestricted activity and who were not candidates for or did not choose hip resurfacing. Patients were followed every second year and assessed with radiographs, Harris Hip Score, WOMAC, SF-12, and UCLA functional outcome scores. Patients were asked about symptoms of instability and satisfaction with their hip replacement. Patients were asked both preoperatively and 2 years postoperatively four questions about their sexual activity. Mean follow-up was 11 years. At 2 years' postoperatively, 98% of patients reported their satisfaction as excellent or good and 99% were not limited for sexual activity following surgery. Seventy-four percent of patients reported they were recovered within 6 weeks of surgery. There were no dislocations. There were three revision procedures for implant loosening, infection, and periprosthetic fracture, but there were no failures of the tripolar articulation. The mean postoperative UCLA score was the highly athletic score of 8. There were no signs of osteolysis, wear, or metal sensitivity reactions. The range of motion achieved, sexual, and functional outcomes were higher than with other types of total hip replacement. This ceramic-coated tripolar prosthesis using highly cross-linked polyethylene provides full function, complete stability, and low wear to younger, active patients, thus confirming the hypothesis and clinical relevance.

Hip Resurfacing Using Highly Cross-linked Polyethylene: Prospective Study Results at 8.5 Years.

BACKGROUND: Hip resurfacing is an option to consider when treating younger, more active patients. Advantages over total hip arthroplasty include a more normal gait and a lower incidence of thigh pain. METHODS: In this prospective study, 190 hip resurfacing procedures (164 participants) were performed using a cobalt-chromium femoral component and a cementless acetabular cup with a 3.8-mm highly cross-linked polyethylene acetabular liner. RESULTS: The mean follow-up was 8.5 (range, 7-10) years. Two participants were lost to follow-up and 2 died. One participant underwent successful revision surgery for acetabular loosening. Four participants underwent successful revision to a total hip arthroplasty because of femoral neck fracture (2), femoral loosening, or infection. The Kaplan-Meier survivorship was 97%. Acetabular bone conservation was assessed using computed tomography by measuring the medial acetabular wall. The mean thickness was 9 mm. Femoral bone was well preserved with a mean head:neck ratio of 1.37. There were 4 (2%) osteolytic defects up to 0.9 cm(3) on computed tomography and no instances of impending polyethylene wear-through. Seven polyethylene retrievals had a measured wear rate of 0.05 mm/y. CONCLUSION: Hip resurfacing using a highly cross-linked polyethylene acetabular component is a reliable procedure. Both femoral and acetabular bones are reasonably preserved compared with prior resurfacing methods. The low incidence of osteolysis and the low rate of wear found on retrievals suggest that many years of use in highly active patients is possible.

Salvage of Monoblock Metal-on-Metal Acetabular Components Using a Dual-Mobility Bearing.

BACKGROUND: Large-diameter, monoblock acetabular components have been used for both hip resurfacing arthroplasty and metal-on-metal (MoM) total hip arthroplasty (THA). If revision is required, one solution is to retain the shell and use a dual-mobility bearing. METHODS: We reviewed the results of 25 revision THAs including 11 hip resurfacing arthroplasty and 14 MoM THAs where a monoblock acetabular component was mated to a dual-mobility bearing. RESULTS: At a mean of 29 months, there was one failure, an intraprosthetic dislocation of the dual-mobility bearing. There was a significant decrease in serum metal ion levels postoperatively. CONCLUSION: Retention of a well-fixed, monoblock MoM acetabular shell and mating it to a dual-mobility bearing in the setting of revision surgery seems to be a reasonable, low-morbidity option at short-term follow-up in appropriately positioned cups.

Bicruciate-retaining Total Knee Replacement Provides Satisfactory Function and Implant Survivorship at 23 Years.

BACKGROUND: One of the goals of a TKA is to approximate the function of a normal knee. Preserving the natural ligaments might provide a method of restoring close to normal function. Sacrifice of the ACL is common and practical during a TKA. However, this ligament is functional in more than 60% of patients undergoing a TKA and kinematic studies support the concept of bicruciate-retaining (that is, ACL-preserving) TKA; however, relatively few studies have evaluated patients treated with bicruciate-retaining TKA implants. QUESTIONS/PURPOSES: I asked: (1) what is the long-term (minimum 20-year) survivorship, (2) what are the functional results, and (3) what are the reasons for revision of bicruciate-retaining knee arthroplasty prostheses? METHODS: From January 1989 to September 1992, I performed 639 total knee replacements in 537 patients. Of these, 489 were performed in 390 patients using a bicruciate-retaining, minimally constrained device. During the period in question, this knee prosthesis was used for all patients observed intraoperatively to have an intact, functional ACL with between 15° varus and 15° valgus joint deformity. There were 234 women and 156 men with a mean age at surgery of 65 years (range, 42-84 years) and a primary diagnosis of osteoarthritis in 89%. The patella was resurfaced in all knees. The mean followup was 23 years (range, 20-24 years). At the time of this review, 199 (51%) patients had died and 31 (8%) patients were lost to followup, leaving 160 (41%) patients (214 knees) available for review. Component survivorship was determined by competing-risks analysis and Kaplan Meier survivorship analysis with revision for any reason as the primary endpoint. Patients were evaluated every 2 years to assess ROM, joint laxity, knee stability, and to determine American Knee Society scores. RESULTS: The Kaplan-Meier survivorship was 89% (95% CI, 82%-93%) at 23 years with revision for any reason as the endpoint. Competing-risks survivorship was 94% (95% CI, 91%%-96 %) at 23 years. At followup, the mean age of the patients was 84 years (range, 63-101 years), the mean flexion was 117° (range, 90°-130°), the mean American Knee Society score improved from a preoperative mean of 42 (range, 26-49) to 91 (range, 61-100; p < .001). Twenty-two knees in 21 patients (5.6%) were revised, most commonly because of polyethylene wear. CONCLUSIONS: ACL sacrifice may be an unnecessary concession during TKA. This study found satisfactory survivorship and function after more than 20 years of use for patients receiving a bicruciate-retaining TKA implant. A TKA that preserves cruciate ligaments provides a stable, well-functioning knee with a low likelihood of revision at long-term followup. Retaining both cruciate ligaments during knee arthroplasty is an attractive concept that is worth considering. LEVEL OF EVIDENCE: Level IV, therapeutic study.

One-component revision of failed hip resurfacing from adverse reaction to metal wear debris.

This study assessed the results of 90 one-component revisions for failed hip resurfacing due to adverse reaction to metal wear debris (76 acetabular, 14 femoral). Patients with a femoral head size 40-45 mm (n=33) received a two-piece titanium meshed shell with a cross-linked polyethylene liner and patients with femoral head size 46-54 mm (n=43) received metal-on-metal components. Patients with femoral head size>45 mm who wished a metal-polyethylene bearing received a dual mobility femoral prosthesis. The mean follow-up was 61 months and the procedure was successful in 97% of the patients. Three failures required re-revision; there was one deep infection. There were no dislocations. One-component revision is a reasonable alternative to revision to total hip arthroplasty.

Osteopontin is a novel downstream target of SOX9 with diagnostic implications for progression of liver fibrosis in humans.

UNLABELLED: Osteopontin (OPN) is an important component of the extracellular matrix (ECM), which promotes liver fibrosis and has been described as a biomarker for its severity. Previously, we have demonstrated that Sex-determining region Y-box 9 (SOX9) is ectopically expressed during activation of hepatic stellate cells (HSC) when it is responsible for the production of type 1 collagen, which causes scar formation in liver fibrosis. Here, we demonstrate that SOX9 regulates OPN. During normal development and in the mature liver, SOX9 and OPN are coexpressed in the biliary duct. In rodent and human models of fibrosis, both proteins were increased and colocalized to fibrotic regions in vivo and in culture-activated HSCs. SOX9 bound a conserved upstream region of the OPN gene, and abrogation of Sox9 in HSCs significantly decreased OPN production. Hedgehog (Hh) signaling has previously been shown to regulate OPN expression directly by glioblastoma (GLI) 1. Our data indicate that in models of liver fibrosis, Hh signaling more likely acts through SOX9 to modulate OPN. In contrast to Gli2 and Gli3, Gli1 is sparse in HSCs and is not increased upon activation. Furthermore, reduction of GLI2, but not GLI3, decreased the expression of both SOX9 and OPN, whereas overexpressing SOX9 or constitutively active GLI2 could rescue the antagonistic effects of cyclopamine on OPN expression. CONCLUSION: These data reinforce SOX9, downstream of Hh signaling, as a core factor mediating the expression of ECM components involved in liver fibrosis. Understanding the role and regulation of SOX9 during liver fibrosis will provide insight into its potential modulation as an antifibrotic therapy or as a means of identifying potential ECM targets, similar to OPN, as biomarkers of fibrosis.

A comparison of the noise generated from different types of knee prostheses.

After total knee arthroplasty (TKA), patients may experience noise from their replaced knee. A prospective study was conducted with 465 (930 knees) patients to evaluate noise after bilateral TKA. A different randomly selected prosthesis was used on each side. The prostheses used were medial pivot (MP), anterior and posterior cruciate ligament retaining (ACL-PCL), posterior cruciate ligament retaining (PCL), posterior cruciate-substituting (PS), or mobile bearing (MB). The evaluation included the patients' responses to questions about noise after both their TKAs. Noise-related symptoms were reported by 12% of the patients with MP prostheses, 4% of patients with ACL-PCL, 31% of patients with PCL, 33% of patients with PS, and 42% of patients with MB. Occasionally, patients were concerned or dissatisfied with this phenomenon. Noise was less common with TKAs that used MP and ACL-PCL knee prostheses than with TKAs that used other prostheses.

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.

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.

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.

A promising thumb Basal joint hemiarthroplasty for treatment of trapeziometacarpal osteoarthritis.

BACKGROUND: Trapeziometacarpal joint osteoarthritis is a painful, disabling condition that primarily affects women who are postmenopausal. Arthroplasty has been performed to treat this condition; however, subluxation has been a problem with all previous implants. We report the results of hemiarthroplasty using a prosthesis designed to address the problems associated with previous implants. QUESTIONS/PURPOSES: We wished to (1) determine if this prosthesis results in pain relief and functional improvement and preserves the appearance of the thumb, (2) assess the prosthetic reconstruction during followup, (3) assess complications that occur with the use of this prosthesis, and (4) determine the survivorship of this prosthesis. METHODS: We performed 159 basal joint hemiarthroplasties (138 patients) to treat osteoarthritis of the trapeziometacarpal joint. The mean age of the patients was 63 years, 78% were women, and all had Eaton-Littler Stage II or III changes. Only the damaged articular surfaces of the metacarpal and trapezium were excised; no tendon grafts or transfers were performed. Seven patients (seven thumbs) were lost to followup and seven (nine thumbs) died, leaving 124 patients (143 thumbs) for review. Clinical and radiographic assessments were made preoperatively, 12 weeks postoperatively, and annually thereafter. Minimum followup was 35 months (mean, 72.1 months; range, 35-120 months). RESULTS: At latest followup, pain relief occurred in 135 thumbs, function improved in 138 thumbs, 139 thumbs were excellent or good in overall assessment, and 142 thumbs had good or excellent cosmetic appearance. The mean tip pinch improved from 4.9 kg preoperatively to 6.44 kg postoperatively. Mean postoperative Buck-Gramcko score was 49 (excellent); overall Kaplan-Meier analysis with revision as the end point showed 94% implant survivorship at a mean followup of 72.1 months. CONCLUSIONS: Our results are superior to those of other implants and support continued use of this implant. Studies with longer followup are required to confirm these results. LEVEL OF EVIDENCE: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.

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.