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Periprosthetic joint infection (PJI) represents a devastating complication of total joint arthroplasty associated with significant morbidity and mortality. Literature suggests a possible higher incidence of periprosthetic joint infection (PJI) in patients with rheumatoid arthritis (RA). There is, however, no consensus on this purported risk nor a well-defined mechanism. This study investigates how collagen-induced arthritis (CIA), a validated animal model of RA, impacts infectious burden in a well-established model of PJI. Control mice were compared against CIA mice. Whole blood samples were collected to quantify systemic IgG levels via ELISA. Ex vivo respiratory burst function was measured via dihydrorhodamine assay. Ex vivo Staphylococcus aureus Xen36 burden was measured directly via colony forming unit (CFU) counts and crystal violet assay to assess biofilm formation. In vivo, surgical placement of a titanium implant through the knee joint and inoculation with S. aureus Xen36 was performed. Bacterial burden was then quantified by longitudinal bioluminescent imaging. Mice with CIA demonstrated significantly higher levels of systemic IgG compared with control mice (p = 0.003). Ex vivo, there was no significant difference in respiratory burst function (p = 0.89) or S. aureus bacterial burden as measured by CFU counts (p = 0.91) and crystal violet assay (p = 0.96). In vivo, no significant difference in bacterial bioluminescence between groups was found at all postoperative time points. CFU counts of both the implant and the peri-implant tissue were not significantly different between groups (p = 0.82 and 0.80, respectively). This study demonstrated no significant difference in S. aureus infectious burden between mice with CIA and control mice. These results suggest that untreated, active RA may not represent a significant intrinsic risk factor for PJI, however further mechanistic translational and clinical studies are warranted.

Tannic acid (TA)–Fe3+ membranes have received recent attention due to their sustainable method of fabrication, high water flux and organic solutes rejection performance. In this paper, we present a description of the transport of aqueous solutions of dyes through these membranes using the transport parameters of the Spiegler–Kedem–Katchalsky (SKK) model. The reflection coefficient (σ) and solute permeability (PS) of the considered TA–Fe3+ membranes were estimated from the non-linear model equations to predict the retention of solutes. The coefficients σ and PS depended on the porous medium and dye molecular size as well as the charge. The simulated rejections were in good agreement with the experimental findings. The model was further validated at low permeate fluxes as well as at various feed concentrations. Discrepancies between the observed and simulated data were observed at low fluxes and diluted feed solutions due to limitations of the SKK model. This work provides insights into the mass transport mechanism of dye solutions and allows the prediction of dye rejection by the TFC membranes containing a TA–Fe3+ selective layer using an SKK model.

Evidence suggests the renin-angiotensin system (RAS) plays key immunomodulatory roles. In particular, angiotensin-converting enzyme (ACE) has been shown to play a role in antimicrobial host defense. ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) are some of the most commonly prescribed medications, especially in patients undergoing invasive surgery. Thus, the current study assessed the immunomodulatory effect of RAS-modulation in a preclinical model of implant infection. antimicrobial effects of ACEi and ARBs were first assessed. C57BL/6J mice subsequently received either an ACEi (lisinopril; 16 mg/kg/day), an ARB (losartan; 30 mg/kg/day), or no treatment. Conditioned mice blood was then utilized to quantify respiratory burst function as well as Xen36 burden in each treatment group. infectious burden for each treatment group was then assessed using a validated mouse model of implant infection. Real-time quantitation of infectious burden via bioluminescent imaging over the course of 28 days post-procedure was assessed. Host response via monocyte and neutrophil infiltration within paraspinal and spleen tissue was quantified by immunohistochemistry for F4/80 and myeloperoxidase, respectively. Blood from mice treated with an ACEi demonstrated a decreased ability to eradicate bacteria when mixed with Xen36 as significantly higher levels of colony forming units (CFU) and biofilm formation was appreciated ( < 0.05). Mice treated with an ACEi showed a higher infection burden at all times ( < 0.05) and significantly higher CFUs of bacteria on both implant and paraspinal tissue at the time of sacrifice ( < 0.05 for each comparison). There was also significantly decreased infiltration and respiratory burst function of immune effector cells in the ACEi group ( < 0.05). ACEi, but not ARB, treatment resulted in increased burden and impaired immune response in a preclinical model of implant infection. These results suggest that perioperative ACEi use may represent a previously unappreciated risk factor for surgical site infection. Given the relative interchangeability of ACEi and ARB from a cardiovascular standpoint, this risk factor may be modifiable.

Bacterial biofilms on orthopedic implants are resistant to the host immune response and to traditional systemic antibiotics. Novel therapies are needed to improve patient outcomes. TRL1068 is a human monoclonal antibody (mAb) against a biofilm anchoring protein. For assessment of this agent in an orthopedic implant infection model, efficacy was measured by reduction in bacterial burden of Staphylococcus aureus, the most common pathogen for prosthetic joint infections (PJI). Systemic treatment with the biofilm disrupting mAb TRL1068 in conjunction with vancomycin eradicated S. aureus from steel pins implanted in the spine for 26 of 27 mice, significantly more than for vancomycin alone. The mechanism of action was elucidated by two microscopy studies. First, TRL1068 was localized to biofilm using a fluorescent antibody tag. Second, a qualitative effect on biofilm structure was observed using scanning electron microscopy (SEM) to examine steel pins that had been treated in vivo. SEM images of implants retrieved from control mice showed abundant three-dimensional biofilms, whereas those from mice treated with TRL1068 did not. Clinical Significance: TRL1068 binds at high affinity to S. aureus biofilms, thereby disrupting the three-dimensional structure and significantly reducing implant CFUs in a well-characterized orthopedic model for which prior tested agents have shown only partial efficacy. TRL1068 represents a promising systemic treatment for orthopedic implant infection.

Thin-film composite (TFC) membranes containing a metal–polyphenol network (MPN)-based selective layer were fabricated on a porous polyacrylonitrile support. The MPN layer was formed through coordination-based self-assembly between plant-based tannic acid (TA) and an Fe3+ ion. For the first time, we demonstrate that TFC membranes containing TA-Fe3+ selective layers can separate small organic solutes in aqueous media from equimolar mixtures of solutes. The effect of the assembly time on the characteristics and performance of the fabricated selective layer was investigated. An increase in the assembly time led to the formation of selective layers with smaller effective pore sizes. The tannic acid–Fe3+ selective layer exhibited a low rejection towards neutral solutes riboflavin and poly(ethylene glycol) while high rejections were observed for anionic dyes of orange II and naphthol green B. Permeation selectivities in the range of 2–27 were achieved between neutral and charged dyes in both single- and mixed-solute experiments, indicating the significant role of Donnan exclusion and the charge-selective nature of the membranes. The rejection efficiency improved with an increasing assembly time. Overall, this study demonstrates that the assembly time is a vital casting parameter for controlling the permeance, rejection and selectivity of thin-film composite membranes with a tannic acid–Fe3+ selective layer.

Purpose To utilise a large cross-sectional database to analyse the effects of time duration between diagnosis of anterior cruciate ligament (ACL) tear and ACL reconstruction (ACLR) on concomitant procedures performed and subsequent surgery within 2 years. Methods An analysis from 2015 to 2018 was performed using the Mariner PearlDiver Patient Records Database. Current Procedural Terminology (CPT), and International Classification of Diseases (ICD-10) codes identified patients with a diagnosis of ACL tear who underwent subsequent ACLR. Patients were stratified in biweekly and bimonthly increments based on the time duration between initial diagnosis of ACL tear and surgical treatment. Chi-squared analysis was used to compare categorical variables, and trend analysis was performed with Cochran–Armitage independence testing. Results Of 11,867 patients who underwent ACLR, 76.1% underwent surgery within 2 months of injury diagnosis. Patients aged 10–19 were most likely to undergo surgery within 2 months of injury diagnosis (83.5%, P  < 0.0001). As duration from injury diagnosis to ACLR increased from < 2 months to > 6 months, rates of concomitant meniscectomy increased from 9.1% to 20.5% ( P  < 0.0001). The overall 2-year subsequent surgery rate was 5.3%. The incidence of revision ACLR was highest for patients who underwent surgery > 6 months after diagnosis ( P  < 0.0001), whilst the incidence of ipsilateral lysis of adhesions and manipulation under anaesthesia (MUA) was highest for patients who underwent surgery < 2 months after diagnosis ( P  < 0.0001). ACLR at 6–8 weeks after diagnosis demonstrated the lowest risk for concomitant procedures as well as 2-year subsequent surgery. Conclusion The majority of patients undergo ACL reconstruction within 2 months of initial ACL tear diagnosis. Delayed surgery greater than 6 months after the diagnosis of an ACL rupture leads to increased need for concomitant meniscectomy as well as higher risk for revision ACLR within 2 years, but immediate surgery may increase risk for knee arthrofibrosis. Level of evidence IV

Vitamin K has been implicated in skeletal health because vitamin K-dependent proteins are present in bone tissue. While there are multiple forms of vitamin K, most research has focused on phylloquinone, which is found mainly in plant-based foods, and its metabolite menaquinone-4 (MK4). However, there are additional forms of vitamin K that are bacterially produced that appear to influence bone health but have not yet been studied extensively. Herein, we evaluated the effects of menaquinone-9 (MK9), a bacterially produced form of vitamin K, on bone tissue quality and density in young mice. Four-week-old male (n = 32) and female (n = 32) C57BL/6 mice were supplemented with 0.06 mg/kg diet or 2.1 mg/kg diet of MK9 for 12 wk. During week 11, a subgroup of mice (n = 7/sex/group) received daily deuterium-labeled MK9 to trace its metabolic fate in bone. Liver MK4 and MK9 were significantly higher in mice fed 2.1 mg MK9/kg compared to those receiving 0.06 mg MK9/kg, regardless of sex (all p ≤ .017). MK4 was the only vitamin K form detected in bone, with 63%-67% of skeletal MK4 in mice fed 2.1 mg MK9/kg derived from deuterium-labeled MK9. Femoral tissue strength, maximum bending moment, section modulus, and BMD did not differ significantly between diet groups in either sex (all p ≥ .083). Cross-sectional area (p = .003) and moment of inertia (p = .001) were lower in female mice receiving 2.1 mg MK9/kg compared to those receiving 0.06 mg MK9/kg, but no differences were found in male mice. Higher bone MK4 concentrations did not correlate with higher bone tissue quality or density. Despite dietary MK9 being a dietary precursor to MK4 in bone, dietary MK9 supplementation did not affect bone tissue quality or BMD during skeletal development.

Background: Nonoperative and operative treatment modalities have been used for symptom management of adhesive capsulitis, but neither has been shown to significantly alter the long-term natural history. Purpose/Hypothesis: The purpose was to evaluate the current trends in resource and treatment strategy utilization for patients with adhesive capsulitis. It was hypothesized that (1) patients with idiopathic adhesive capsulitis will primarily undergo nonoperative treatment and (2) patients with systemic medical comorbidities will demonstrate relatively higher utilization of nonoperative therapies. Study Design: Cross-sectional study; Level of evidence, 3. Methods: We searched the Mariner/PearlDiver database for Current Procedural Terminology and International Classification of Diseases codes to identify patients with adhesive capsulitis from 2010 to 2020 and to track their usage of diagnostic and therapeutic modalities, including radiography, magnetic resonance imaging (MRI), physical therapy, surgery, opioids, and injection. Patients with active records 1 year before and 2 years after initial diagnosis of adhesive capsulitis were eligible. Excluded were patients with secondary causes of adhesive capsulitis, such as fracture, infection, prior surgery, or other intra-articular pathology. Results: The median age of this 165,937-patient cohort was 58 years, with 67% being women. There was a high prevalence of comorbid diabetes (44.2%), thyroid disorder (29.6%), and Dupuytren contracture (1.3%). Within 2 years of diagnosis of adhesive capsulitis, diagnostic and therapeutic modality utilization included radiography (47.2%), opioids (46.7%), physical therapy (43.1%), injection (39.0%), MRI (15.8%), arthroscopic surgery (2.7%), and manipulation under anesthesia (2.5%). Over 68% of the diagnostic and therapeutic modalities were rendered from 3 months before to 3 months after diagnosis. Patients with diabetes, thyroid disorders, tobacco use, and obesity had greater odds for treatment with physical therapy, opioids, radiography, and injection when compared with patients without these comorbidities (odds ratio [OR] range, 1.05-2.21; P < .0001). Patients with diabetes and thyroid disorders had decreased odds for surgery (OR range, 0.88-0.91; P ≤ .003). Patients with Dupuytren contracture had increased odds for all therapeutic modalities (OR range, 1.20-1.68; P < .0001). Conclusion: Patients with adhesive capsulitis underwent primarily nonoperative treatment, with a high percentage utilizing opioids. The most active periods for treatment were from 3 months before diagnosis to 3 months after, and patients with medical comorbidities were more likely to undergo nonoperative treatment.

In a recent study examining the effects of manipulating the gut microbiome on bone, a control group of mice in which the microbiome was altered using a non-caloric, aspartame-based sweetener resulted in whole bone strength being 40% greater than expected from geometry alone, implicating enhanced bone tissue strength. However, the study was not designed to detect changes in bone in this control group and was limited to young male mice. Here we report a replication study examining how changes in the gut microbiome caused by aspartame-based sweetener influence bone. Male and female C57Bl/6 J mice were untreated or treated with a high dose of sweetener (10 g/L) in their drinking water from either 1 to 4 mo of age (young cohort; n = 80) or 1 to 22 mo of age (aged cohort; n = 52). Sweetener did not replicate the modifications to the gut microbiome observed in the initial study and did not result in an increase in bone tissue strength in either sex at either age. Aged male mice dosed with sweetener had larger bones (+17% femur section modulus, p<.001) and greater whole bone strength (+22%, p=.006) but the increased whole bone strength was explained by the associated increase in body mass (+9%, p<.001). No differences in body mass, whole bone strength, or femoral geometry were associated with sweetener dosing in males from the young cohort or females at either age. As we were unable to replicate the gut microbiota observed in the initial experiment, it remains unclear if changes in the gut microbiome can enhance bone tissue strength. Although prior work studying gut microbiome–induced changes in bone with oral antibiotics has been highly repeatable, the current study highlights the variability of nutritional manipulations of the gut microbiota in mice.

Background: There is a lack of research investigating current practice trends in the treatment of anterior cruciate ligament (ACL) tears as well as common concomitant procedures and reoperations associated with ACL reconstruction (ACLR). Purpose: To analyze current practice patterns for ACLR as well as the frequency of concomitant and revision procedures with respect to patient characteristics in a cross-sectional population of the United States. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Patient data between 2010 and 2017 were queried using the Mariner PearlDiver database. International Classification of Diseases, Ninth Revision (in 2010-2014) and Tenth Revision (ICD-10; in 2015-2017), diagnosis codes were used to identify ACL tears, and Current Procedural Terminology codes were used to identify ACLR and concomitant surgical procedures. Patient characteristics were stratified by sex and age. Cases of subsequent knee surgery and conversion to total knee arthroplasty (TKA) within 2 years after ACLR were tracked using ICD-10 codes between 2015 and 2017 to ensure ipsilateral laterality. Results: Of 229,295 patients identified with an ACL tear diagnosis during the study period, 75% underwent ACLR. In patients aged 10 to 39 years, 84% to 92% underwent ACLR, while patients aged 50 to 59 (50%) and 60 to 69 (28%) years were less likely to have surgery after an ACL tear. Female and male patients underwent ACLR at a similar rate (75%). Within the patients who underwent ACLR, 44% underwent concomitant meniscal debridement as compared with 11% with concomitant meniscal repair. Male patients were more likely to undergo meniscal debridement (48% vs 40%; P < .0001). The frequency of meniscal repair increased from 9% in 2010 to 14% in 2017, while the frequency of meniscal debridement decreased from 47% to 41% (P < .0001). Within 2 years of ACLR, 6% of patients underwent revision ACLR; 4%, subsequent meniscal debridement; 1%, meniscal repair; and 1%, conversion to TKA. Conclusion: The frequency of ACLR for ACL tears has remained relatively stable in recent years and was similar between female and male patients in this cross-sectional population. The majority of patients aged 10 to 39 years underwent ACLR, while less than half of patients >50 years underwent surgery.