ABSTRACT
Sex steroids modulate the distribution of mammalian white adipose tissues. Moreover, WAT remodeling requires adipocyte progenitor cells. Nevertheless, the sex-dependent mechanisms regulating adipocyte progenitors remain undetermined. Here, we uncover Cxcr4 acting in a sexually dimorphic manner to affect a pool of proliferating cells leading to restriction of female fat mass. We find that deletion of Cxcr4 in Pparγ-expressing cells results in female, not male, lipodystrophy, which cannot be restored by high-fat diet consumption. Additionally, Cxcr4 deletion is associated with a loss of a pool of proliferating adipocyte progenitors. Cxcr4 loss is accompanied by the upregulation of estrogen receptor alpha in adipose-derived PPARγ-labelled cells related to estradiol hypersensitivity and stalled adipogenesis. Estrogen removal or administration of antiestrogens restores WAT accumulation and dynamics of adipose-derived cells in Cxcr4-deficient mice. These findings implicate Cxcr4 as a female adipogenic rheostat, which may inform strategies to target female adiposity.
Subject(s)
Adipocytes , Adipogenesis , Adiposity , PPAR gamma , Receptors, CXCR4 , Stem Cells , Animals , Receptors, CXCR4/metabolism , Receptors, CXCR4/genetics , Female , Male , Mice , Adipocytes/metabolism , Adipocytes/cytology , Stem Cells/metabolism , Stem Cells/cytology , PPAR gamma/metabolism , PPAR gamma/genetics , Mice, Knockout , Adipose Tissue, White/metabolism , Adipose Tissue, White/cytology , Diet, High-Fat/adverse effects , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/genetics , Mice, Inbred C57BL , Estradiol/pharmacology , Estradiol/metabolism , Cell Proliferation , Sex Factors , Sex CharacteristicsABSTRACT
Human interpersonal capacities emerge from coordinated neural, biological, and behavioral activity unfolding within and between people. However, developmental research to date has allocated comparatively little focus to the dynamic processes of how social interactions emerge across these levels of analysis. Second-person neuroscience and dynamic systems approach together to offer an integrative framework for addressing these questions. This study quantified respiratory sinus arrhythmia and social behavior (â¼360 observations per system) from 44 mothers and typically developing 9-month-old infants during a novel modified "still-face" (text message perturbation) task. Stochastic autoregression models indicate that the infant parasympathetic nervous system is coupled within and between people second by second and is sensitive to social context. Intraindividual, we found positive coupling between infants' parasympathetic nervous system activity and their social behavior in the subsequent second, but only during the moments and periods of active caregiver engagement. Between people, we found a bidirectional coregulatory feedback loop: Mothers' parasympathetic activity positively predicted that of their infant in the subsequent second, a form of synchrony that decreased during the text message perturbation and did not fully recover. Conversely, infant parasympathetic activity negatively predicted that of their mother at the subsequent second, a form of synchrony that was invariant over social context. Findings reveal unidirectional parasympathetic coupling within infants and a complementary allostatic feedback loop between mother and infant parasympathetic systems. They offer novel evidence of a dynamic, socially embedded parasympathetic system at previously undocumented timescales, contributing to both basic science and potential clinical targets to better support adaptive, multisystem social development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
ABSTRACT
Objective: Platelet Derived Growth Factor Receptor Beta (Pdgfrß) suppresses the formation of cold temperature-induced beige adipocytes in aged mammals. We aimed to determine if deleting Pdgfrß in aged mice could rejuvenate metabolically active beige adipocytes by activating group 2 innate lymphoid cells (ILC2), and whether this effect could counteract diet-induced obesity-associated beige fat decline. Methods: We employed Pdgfrß gain-of-function and loss-of-function mouse models targeting beige adipocyte progenitor cells (APCs). Our approach included cold exposure, metabolic cage analysis, and age and diet-induced obesity models to examine beige fat development and metabolic function under varied Pdgfrß activity. Results: Acute cold exposure alone enhanced metabolic benefits in aged mice, irrespective of beige fat generation. However, Pdgfrß deletion in aged mice reestablished the formation of metabolically functional beige adipocytes, enhancing metabolism. Conversely, constitutive Pdgfrß activation in young mice stymied beige fat development. Mechanistically, Pdgfrß deletion upregulated IL-33, promoting ILC2 recruitment and activation, whereas Pdgfrß activation reduced IL-33 levels and suppressed ILC2 activity. Notably, diet-induced obesity markedly increased Pdgfrß expression and Stat1 signaling, which inhibited IL-33 induction and ILC2 activation. Genetic deletion of Pdgfrß restored beige fat formation in obese mice, improving whole-body metabolism. Conclusion: This study reveals that cold temperature exposure alone can trigger metabolic activation in aged mammals. However, reversing Pdgfrß signaling in aged and obese mice not only restores beige fat formation but also renews metabolic function and enhances the immunological environment of white adipose tissue (WAT). These findings highlight Pdgfrß as a crucial target for therapeutic strategies aimed at combating age- and obesity-related metabolic decline.
ABSTRACT
Childhood and adolescence are salient periods for the development of adrenocortical and autonomic arms of the stress response system (SRS), setting the stage for subsequent health and adaptive functioning. Although adrenocortical and autonomic systems theoretically function in highly coordinated ways, the strength of the relationship between these systems remains unclear. We leveraged a multivariate mixed effects meta-analytic approach to assess associations between adrenocortical, sympathetic, and parasympathetic functioning at rest and reactivity during stress-inducing tasks across 52 studies (N = 7,671; 5-20 years old). Results suggested a modest positive relation between adrenocortical and sympathetic systems as well as between adrenocortical and parasympathetic systems. Moderation analyses indicated the strength of associations varied as a function of several methodological and sociodemographic characteristics. Environmental effects on cross-system regulation were less clear, perhaps due to underrepresentation of adverse-exposed youth in the included studies. Collectively, our findings call for greater methodological attention to the dynamical, non-linear nature of cross-system functioning, as well as the role of experience in their organization across development.
Subject(s)
Autonomic Nervous System , Stress, Psychological , Humans , Adolescent , Child , Autonomic Nervous System/physiology , Young Adult , Stress, Psychological/physiopathology , Stress, Psychological/metabolism , Male , Female , Child, Preschool , Sympathetic Nervous System/physiology , Adrenal Cortex/physiology , Parasympathetic Nervous System/physiologyABSTRACT
BACKGROUND: Modular fluted tapered (MFT) femoral components are frequently utilized in aseptic revision total hip arthroplasties (THAs). However, long-term follow-up has been limited. The purpose of this study was to update our prior series at long-term follow-up, with specific emphasis on implant survivorship, radiographic results, and complications in a large cohort of aseptic revision THAs using MFT stems. METHODS: We retrospectively identified 515 aseptic femoral revisions performed with 2 MFT stem designs in the total joint registry of a single tertiary care academic institution from 1999 to 2013. Serial radiographs were reviewed for subsidence of >5 mm. The mean follow-up (and standard deviation) was 10 ± 5 years (range, 2 to 21 years). A competing risk model accounting for death was utilized. RESULTS: The 15-year cumulative incidence of any revision was 12%. There were 57 revisions, 27 of which involved revision of the fluted tapered component (FTC). Dislocation (n = 19), periprosthetic joint infection (n = 15), and aseptic loosening of the FTC (n = 11) were the most common reasons for revision. The 15-year cumulative incidence of any reoperation was 16%. The 15-year cumulative incidences were 6% for any FTC revision and 2% for FTC revision for aseptic loosening. Stem subsidence of >5 mm occurred in 2% of unrevised cases, and all but 1 stem was stable at the most recent follow-up. CONCLUSIONS: This large series of MFT stems used in aseptic revision THAs had a 2% incidence of subsequent revision of the FTC for aseptic loosening at 15 years. Dislocation and infection were the most common reasons for any revision. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
ABSTRACT
The number of revision total knee arthroplasties (TKAs) performed annually continues to rise. This article is a summary of a symposium on revision TKAs presented at the 2023 American Association of Hip and Knee Surgeons annual meeting. It will provide an overview of the surgical tips and tricks for exposure and component removal, use of metaphyseal fixation and stems to manage bone loss and optimize fixation, constraint in TKA, as well as how to manage extensor mechanism disruptions with a synthetic mesh reconstruction. LEVEL OF EVIDENCE: V.
ABSTRACT
BACKGROUND: Most periprosthetic fractures following total hip arthroplasty (THA) are fragility fractures that qualify patients for osteoporosis diagnoses. However, it remains unknown how many patients were diagnosed who had osteoporosis before injury or received the proper evaluation, diagnosis, and treatment after injury. METHODS: We identified 171 Vancouver B2 (109) and B3 (62) periprosthetic femur fractures treated with a modular fluted tapered stem from 2000 to 2018 at 1 institution. The mean patient age was 75 years (range, 35 to 94), 50% were women, and the mean body mass index was 29 (range, 17 to 60). We identified patients who had osteoporosis or osteopenia diagnoses, a fracture risk assessment tool (FRAX), bone mineral density (BMD) testing, an endocrinology consult, and osteoporosis medications. Age-appropriate BMD testing was defined as no later than 1 year after the recommended ages of 65 (women) or 70 years (men). The mean follow-up was 11 years (range, 4 to 21). RESULTS: Falls from standing height caused 94% of fractures and thus, by definition, qualified as osteoporosis-defining events. The prevalence of osteoporosis diagnosis increased from 20% before periprosthetic fracture to 39% after (P < .001). The prevalence of osteopenia diagnosis increased from 13% before the fracture to 24% after (P < .001). The prevalence of either diagnosis increased from 24% before fracture to 44% after (P < .001). No patients had documented FRAX scores before fracture, and only 2% had scores after. The prevalence of BMD testing was 21% before fracture and 22% after (P = .88). By the end of the final follow-up, only 16% had received age-appropriate BMD testing. The proportion of patients who had endocrinology consults increased from 6% before the fracture to 25% after (P < .001). The proportion on bisphosphonate therapy was 19% before fracture and 25% after (P = .08). CONCLUSIONS: Although most periprosthetic fractures following THA are fragility fractures that qualify patients for osteoporosis diagnoses, there remain major gaps in diagnosis, screening, endocrinology follow-up, and treatment. Like nonarthroplasty fragility fractures, a systematic approach is needed after periprosthetic fractures. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
ABSTRACT
There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived C-C motif chemokine (CCL22) into iWAT. CCL22 injection into iWAT effectively promotes iWAT beiging, while blocking CCL22 with antibodies can prevent it. Mechanistically, the CCL22 receptor, C-C motif chemokine receptor 4 (CCR4), within eosinophils and its downstream focal adhesion kinase/p65/interleukin-4 signaling are essential for CCL22-mediated beige adipocyte formation. Moreover, CCL22 levels are inversely correlated with body weight and fat mass in mice and humans. Acute elevation of CCL22 levels effectively prevents diet-induced body weight and fat gain by enhancing adipose beiging. Together, our data identify the CCL22-CCR4 axis as an essential mediator for LN-controlled adaptive thermogenesis and highlight its potential to combat obesity and its associated complications.
Subject(s)
Adipose Tissue, White , Chemokine CCL22 , Energy Metabolism , Lymph Nodes , Macrophages , Thermogenesis , Animals , Female , Humans , Male , Mice , Adipocytes, Beige/metabolism , Adipose Tissue, White/metabolism , Chemokine CCL22/metabolism , Eosinophils/metabolism , Lymph Nodes/metabolism , Macrophages/metabolism , Mice, Inbred C57BL , Obesity/metabolism , Receptors, CCR4/metabolism , Signal TransductionABSTRACT
Uncertainty is unavoidable, and maladaptive responses to uncertainty may underlie the etiology and maintenance of psychopathology. A general tendency to associate uncertainty with aversive consequences, a type of covariation bias, can amplify aversive emotional experiences. To address questions about uncertainty during emotion regulation, we examined the Late Positive Potential (LPP) - an electrocortical marker of attention to and appraisal of motivationally relevant emotional stimuli - during a task designed to measure the effect of covariation bias and its emotional response consequences. Event-related potentials (ERPs) were recorded while participants (N = 52) were presented with a pre-stimulus cue that either conveyed information about the valence of an upcoming emotional image, or left them in ambiguity. We replicated findings that demonstrate expectancy biases in a priori and online expectancies of emotion-eliciting images, as well as in a posteriori estimates for concurrence of uncertainty cues and aversive images. Moreover, we demonstrate a novel finding that uncertainty cues amplify the LPP in response to subsequent aversive emotional stimuli. These findings advance research by conjoining existing emotion regulation research on the LPP with study of the effects of uncertainty on emotional appraisal and highlight the importance of accounting for stimulus uncertainty in emotion regulation research.
Subject(s)
Cues , Electroencephalography , Emotions , Evoked Potentials , Humans , Uncertainty , Female , Male , Evoked Potentials/physiology , Emotions/physiology , Young Adult , Adult , Adolescent , Brain/physiology , Photic Stimulation/methodsABSTRACT
BACKGROUND: Metaphyseal cones with cemented stems can be successfully utilized in most revision total knee arthroplasties (TKAs). However, if the diaphysis has been previously violated, fixation of the cemented stem, which is important for cone ingrowth and construct survival, can be compromised. The initial results of our novel technique combining diaphyseal impaction bone-grafting with a metaphyseal cone were promising but required additional study. The purpose of the present study was to assess results of this technique in a larger cohort. METHODS: A metaphyseal cone combined with diaphyseal impaction grafting and a cemented stem was utilized in 88 revision TKAs at our institution, including 35 from our prior study. The mean age at the time of revision was 67 years, and 67% of patients were male. Patients had had a mean of 4 prior knee arthroplasty procedures. The 2 most common reasons for revision were aseptic loosening (78%) and 2-stage reimplantation for periprosthetic joint infection (PJI) (19%). The mean follow-up was 4 years. RESULTS: At the time of the latest follow-up, no cone-impaction grafting constructs required re-revision for aseptic loosening. Five-year survivorship free from any revision of the cone-impaction grafting construct and free from any reoperation was 95% and 65%, respectively. A total of 25 knees (28%) underwent reoperation, with the 2 most common indications being PJI and periprosthetic fracture. All cones were osseointegrated, and all bone graft appeared stable or incorporated. One patient had radiographic evidence of tibial component loosening despite a well-fixed cone; however, this patient was asymptomatic and had not undergone revision at 9 years. CONCLUSIONS: When presented with a sclerotic, polished diaphyseal canal with deficient cancellous bone and concomitant metaphyseal bone loss, our technique of combining diaphyseal impaction grafting with a metaphyseal cone proved extremely durable in this larger series of patients. No cone-impaction grafting constructs required re-revision for aseptic loosening. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Arthroplasty, Replacement, Knee , Bone Transplantation , Diaphyses , Reoperation , Humans , Male , Reoperation/statistics & numerical data , Female , Aged , Bone Transplantation/methods , Arthroplasty, Replacement, Knee/methods , Middle Aged , Diaphyses/surgery , Knee Prosthesis , Prosthesis Failure , Treatment Outcome , Aged, 80 and over , Retrospective Studies , Bone CementsABSTRACT
Importance: Evidence suggests that living near green space supports mental health, but studies examining the association of green space with early mental health symptoms among children are rare. Objective: To evaluate the association between residential green space and early internalizing (eg, anxiety and depression) and externalizing (eg, aggression and rule-breaking) symptoms. Design, Setting, and Participants: Data for this cohort study were drawn from the Environmental Influences on Child Health Outcomes cohort; analysis was conducted from July to October 2023. Children born between 2007 and 2013 with outcome data in early (aged 2-5 years) and/or middle (aged 6-11 years) childhood who resided in 41 states across the US, drawing from clinic, hospital, and community-based cohorts, were included. Cohort sites were eligible if they recruited general population participants and if at least 30 children had outcome and residential address data to measure green space exposure. Nine cohorts with 13 sites met these criteria. Children diagnosed with autism or developmental delay were excluded, and 1 child per family was included. Exposures: Green space exposure was measured using a biannual (ie, summer and winter) Normalized Difference Vegetation Index, a satellite image-based indicator of vegetation density assigned to monthly residential history from birth to outcome assessment. Main Outcome and Measures: Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist for Ages 1½ to 5 or 6 to 18. The association between green space and internalizing and externalizing symptoms was modeled with multivariable linear regression using generalized estimating equations, adjusting for birthing parent educational level, age at delivery, child sex, prematurity, and neighborhood socioeconomic vulnerability. Models were estimated separately for early and middle childhood samples. Results: Among 2103 children included, 1061 (50.5%) were male; 606 (29.1%) identified as Black, 1094 (52.5%) as White, 248 (11.9%) as multiple races, and 137 (6.6%) as other races. Outcomes were assessed at mean (SD) ages of 4.2 (0.6) years in 1469 children aged 2 to 5 years and 7.8 (1.6) years in 1173 children aged 6 to 11 years. Greater green space exposure was associated with fewer early childhood internalizing symptoms in fully adjusted models (b = -1.29; 95% CI, -1.62 to -0.97). No associations were observed between residential green space and internalizing or externalizing symptoms in middle childhood. Conclusions and Relevance: In this study of residential green space and children's mental health, the association of green space with fewer internalizing symptoms was observed only in early childhood, suggesting a sensitive period for nature exposure. Policies protecting and promoting access to green space may help alleviate early mental health risk.
Subject(s)
Aggression , Parks, Recreational , Child , Humans , Child, Preschool , Male , Female , Cohort Studies , Ambulatory Care Facilities , Anxiety/epidemiologyABSTRACT
BACKGROUND: Highly porous metal tibial metaphyseal cones (TMCs) are commonly utilized in revision total knee arthroplasty (TKA) to address bone loss and obtain biologic fixation. Mid-term (5 to 10 year) studies have previously demonstrated excellent survivorship and high rates of osseointegration, but longer-term studies are lacking. We aimed to assess long-term (≥ 10 year) implant survivorship, complications, and clinical and radiographic outcomes after revision TKA with TMCs. METHODS: Between 2004 and 2011, 228 revision TKAs utilizing porous tantalum TMCs with stemmed tibial components were performed at a single institution and were retrospectively reviewed. The mean age at revision was 65 years, the mean body mass index was 33, and 52% were women. Implant survivorship, complications, and clinical and radiographic outcomes were assessed. The mean follow-up was 6.3 years. RESULTS: The 10-year survivorship free of aseptic loosening leading to TMC removal was 97%, free of any TMC removal was 88%, free of any re-revision was 66%, and free of any reoperation was 58%. The most common indications for re-revision were periprosthetic joint infection, instability, and aseptic femoral component loosening. The 10-year nonoperative complication rate was 24%. The mean Knee Society scores increased from 38 preoperatively to 69 at 10 years. There were 8 knees that had evidence of partial, progressive tibial radiolucencies at 10 years. CONCLUSIONS: Porous tantalum TMCs demonstrated persistently durable longer-term survivorship with a low rate of implant removal. The rare implant removals for component loosening or instability were offset by those required for periprosthetic joint infection, which accounted for 80% of cone removals. Porous tantalum TMCs provide an extremely reliable tool to address tibial bone loss and achieve durable long-term fixation in revision TKA. LEVEL OF EVIDENCE: IV.
Subject(s)
Arthroplasty, Replacement, Knee , Knee Prosthesis , Prosthesis Design , Prosthesis Failure , Reoperation , Tantalum , Tibia , Humans , Arthroplasty, Replacement, Knee/instrumentation , Arthroplasty, Replacement, Knee/adverse effects , Female , Aged , Male , Reoperation/statistics & numerical data , Retrospective Studies , Middle Aged , Tibia/surgery , Aged, 80 and over , Porosity , Knee Joint/surgery , Follow-Up Studies , Treatment Outcome , Adult , RadiographyABSTRACT
Sympathetic innervation of brown adipose tissue (BAT) controls mammalian adaptative thermogenesis. However, the cellular and molecular underpinnings contributing to BAT innervation remain poorly defined. Here, we show that smooth muscle cells (SMCs) support BAT growth, lipid utilization, and thermogenic plasticity. Moreover, we find that BAT SMCs express and control the bioavailability of Cxcl12. SMC deletion of Cxcl12 fosters brown adipocyte lipid accumulation, reduces energy expenditure, and increases susceptibility to diet-induced metabolic dysfunction. Mechanistically, we find that Cxcl12 stimulates CD301+ macrophage recruitment and supports sympathetic neuronal maintenance. Administering recombinant Cxcl12 to obese mice or leptin-deficient (Ob/Ob) mice is sufficient to boost macrophage presence and drive sympathetic innervation to restore BAT morphology and thermogenic responses. Altogether, our data reveal an SMC chemokine-dependent pathway linking immunological infiltration and sympathetic innervation as a rheostat for BAT maintenance and thermogenesis.
Subject(s)
Adipose Tissue, Brown , Chemokine CXCL12 , Macrophages , Myocytes, Smooth Muscle , Sympathetic Nervous System , Thermogenesis , Animals , Chemokine CXCL12/metabolism , Macrophages/metabolism , Adipose Tissue, Brown/metabolism , Adipose Tissue, Brown/innervation , Mice , Myocytes, Smooth Muscle/metabolism , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/physiology , Mice, Inbred C57BL , Male , Energy Metabolism , Obesity/metabolism , Obesity/pathologyABSTRACT
AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis. Fifty-six female New Zealand White rabbits were divided into three dosing groups: vehicle (dimethyl sulfoxide, DMSO), 2.5 mg/kg AdipoRon, and 5 mg/kg AdipoRon. AdipoRon, in DMSO, was administered IV preoperatively and for 5 days postoperatively (30 rabbits, Aim 1). AdipoRon was again dosed similarly after Kirschner wire (K-wire) removal at 8 weeks (26 rabbits; Aim 2). The primary outcome of joint passive extension angle (PEA,°) was measured at 8, 10, 12, 16, and 24 weeks following index surgery. At 24 weeks, rabbits were euthanized and limbs were harvested to measure posterior capsular stiffness (N cm/°). In Aim 1, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 16-week (p < 0.05). In Aim 2, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 10-week (p < 0.05). In both aims, no significant differences were observed at later time points. Capsular stiffness was no different in any group. We are the first to report the efficacy of IV AdipoRon in a rabbit model of arthrofibrosis. We identified a significant dose-dependent decrease in joint PEA at early time points; however, no differences were observed between groups at later time points. Clinical Significance: The present investigation provided the first assessment of AdipoRon's efficacy in mitigating knee stiffness in the current gold standard rabbit model of arthrofibrosis. Results of this investigation provided further evidence as to the potential role of AdipoRon as a preventative for arthrofibrosis in large mammals.
Subject(s)
Fibrosis , Receptors, Adiponectin , Animals , Rabbits , Female , Receptors, Adiponectin/agonists , Contracture/prevention & control , Contracture/etiology , Contracture/drug therapy , Disease Models, Animal , Piperidines/therapeutic use , Piperidines/pharmacologySubject(s)
Societies, Medical , Humans , Arthroplasty, Replacement, Hip , Orthopedics , Hip Joint/surgeryABSTRACT
Aims: Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants - modular fluted tapered (MFT) femoral components - in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components. Methods: We identified 236 reimplantation THAs from a single tertiary care academic institution from September 2000 to September 2020. Two designs of MFT femoral components were used as part of an established two-stage exchange protocol for the treatment of PJI. Mean age at reimplantation was 65 years (SD 11), mean BMI was 32 kg/m2 (SD 7), and 46% (n = 109) were female. Mean follow-up was seven years (SD 4). A competing risk model accounting for death was used. Results: The 15-year cumulative incidence of any revision was 24%. There were 48 revisions, with the most common reasons being dislocation (n = 25) and infection (n = 16). The 15-year cumulative incidence of any reoperation was 28%. Only 13 revisions involved the fluted tapered component (FTC), for a 15-year cumulative incidence of any FTC revision of 8%. Only two FTCs were revised for aseptic loosening, resulting in a 15-year cumulative incidence of FTC revision for aseptic loosening of 1%. Stem subsidence ≥ 5 mm occurred in 2% of unrevised cases. All stems were radiologically stable at most recent follow-up. Mean Harris Hip Score was 69 (SD 20) at most recent follow-up. Conclusion: This series demonstrated that MFT components were durable and reliable in the setting of two-stage reimplantation THA for infection. While the incidence of aseptic loosening was very low, the incidence of any revision was 24% at 15 years, primarily due to dislocation and recurrent PJI.
Subject(s)
Arthroplasty, Replacement, Hip , Hip Prosthesis , Prosthesis Design , Prosthesis-Related Infections , Reoperation , Humans , Arthroplasty, Replacement, Hip/instrumentation , Arthroplasty, Replacement, Hip/adverse effects , Female , Prosthesis-Related Infections/surgery , Prosthesis-Related Infections/etiology , Male , Hip Prosthesis/adverse effects , Aged , Middle Aged , Retrospective Studies , Prosthesis FailureABSTRACT
Entomopathogenic fungus Metarhizium majus contains the nine-gene PPZ cluster, with ppzA, encoding a peramine-producing nonribosomal peptide synthetase, as the central component. In this work, the roles of two α-ketoglutarate, iron-dependent oxygenases encoded by the PPZ genes ppzC and ppzD were elucidated. PpzD was found to produce both trans-4-hydroxy-l-proline and trans-3-hydroxy-l-proline in a 13.1:1 ratio, yielding a key precursor for peramine biosynthesis. PpzC was found to act directly on peramine, yielding the novel analogue 8-hydroxyperamine.
Subject(s)
Heterocyclic Compounds, 2-Ring , Iron , Ketoglutaric Acids , Metarhizium , Polyamines , Multigene Family , Ferrous CompoundsABSTRACT
BACKGROUND: Periprosthetic joint infections (PJIs) of total hip arthroplasty (THA) or total knee arthroplasty (TKA) may occur in the setting of an uninfected ipsilateral prosthetic joint. However, the risk to that uninfected ipsilateral joint is unknown. We analyzed the survivorship free from PJI in at risk THAs and TKAs following treatment of an ipsilateral knee or hip PJI, respectively. METHODS: Using our institutional total joint registry, we identified 205 patients who underwent treatment for PJI (123 THAs and 83 TKAs) with an at-risk ipsilateral in situ knee or hip, respectively, between 2000 and 2019. In total, 54% of index PJIs were chronic and 46% were acute. The mean age was 70 years, 47% were female, and the mean body mass index was 32. Kaplan-Meier survivorship analyses were performed. Mean follow-up was 6 years. RESULTS: The 5-year survivorship free of PJI in an at-risk THA after an ipsilateral TKA was treated for PJI was 97%. The 5-year survivorship free of PJI in an at-risk TKA when the ipsilateral THA was treated for PJI was 99%. Three PJIs occurred (2 THAs and 1 TKA), all over 1 year from the index ipsilateral PJI treatment. One hip PJI was an acute hematogenous infection that resulted from pneumonia. The other 2 new PJIs were caused by the same organism as the index PJI and were due to a failure of source control at the index joint. CONCLUSIONS: When diagnosed with PJI in a single joint, the risk of developing PJI in an ipsilateral prosthetic joint within 5 years was low (1 to 3% risk). In the rare event of an ipsilateral infection, all occurred greater than one year from the index PJI and 2 of 3 were with the same organism when source infection control failed. LEVEL OF EVIDENCE: Prognostic Level III.
ABSTRACT
Liquid handler systems can provide significant benefits to researchers by automating laboratory work, however, their unaffordable price provides a steep barrier to entry. Therefore, we provide the BioCloneBot, a versatile, low-cost, and open-source automated liquid handler. This system can be easily built with 3D-printed parts and readily available commercial components. The BioCloneBot is highly adaptive to user needs and facilitates various liquid handling tasks in research and diagnostics. Its user-friendly interface and programmable nature make it suitable for a wide range of applications, from small-scale experiments to larger laboratory setups. By utilizing BioCloneBot, researchers and scientists can streamline their liquid handling processes without the financial constraints posed by traditional systems. In this paper, we detail the design, construction, and validation of BioCloneBot, showcasing its precise control, accuracy, and repeatability in various liquid handling tasks. The open-source nature of the system encourages collaboration and customization, enabling researchers to contribute and adapt the technology to specific experimental requirements.
ABSTRACT
BACKGROUND: Arthroplasty registries often use traditional Medicare (TM) claims data to report long-term total hip arthroplasty (THA) survivorship. The purpose of this study was to determine whether the large number of patients leaving TM for Medicare Advantage (MA) has compromised the fidelity of TM data. METHODS: We identified 10,962 THAs in 9,333 Medicare-eligible patients who underwent primary THA from 2000 to 2020 at a single institution. Insurance type was analyzed, and 83% of patients had TM at the time of THA. Survivorship free from any revision or reoperation was calculated for patients who have TM. The same survivorship end points were recalculated with censoring performed when a patient transitioned to an MA plan after their primary THA to model the impact of losing patients from the TM dataset. Differences in survivorship were compared. The mean follow-up was 7 years. RESULTS: From 2000 to 2020, there was a decrease in TM insurance (93 to 73%) and a corresponding increase in MA insurance (0 to 19%) among THA patients. Following THA, 23% of TM patients switched to MA. For patients who had TM at the time of surgery, 15-year survivorship free from any reoperation or revision was 90% and 93%, respectively. When censoring patients upon transition from TM to MA, survivorship free from any reoperation became significantly higher (92 versus 90% at 15 years; hazard ratio = 1.16, P = .033), and there was a trend toward higher survivorship free from any revision (95 versus 93% at 15 years; hazard ratio = 1.16, P = .074). CONCLUSIONS: Approximately 1 in 4 patients left TM for MA after primary THA, effectively making them lost to follow-up within TM datasets. The mass exodus of patients out of TM appears to have led to a slight overestimation of survivorship free from any reoperation and trended toward overestimating survivorship free from any revision. If MA continues to grow, efforts to obtain MA data will become even more important.