The Immediate Impact of Total Knee Arthroplasty Removal From the Medicare Inpatient-Only List on Patient Derived Functional Outcomes and Hospital Satisfaction.

BACKGROUND: Total knee arthroplasty (TKA) is the standard of treatment for end-stage knee osteoarthritis. On January 1, 2018, the Centers for Medicare and Medicaid (CMS) officially removed TKA from their inpatient-only list. The clinical impact of this change is not fully understood yet. METHODS: Electronic records were retrospectively reviewed for patients who underwent TKA between January 1 to June 30, 2017, or January 1 to June 30, 2018. Patients completed Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement surveys which assessed patient reported outcomes prior to and following TKA. Hospital statistics for the 2 time points were determined and compared. This was a single institution study resulting in 351 patients in the pre-CMS change group and 350 patients in the post-CMS change group. RESULTS: Analysis of the pre-CMS and post-CMS transition cohorts indicated no significant difference in activities of daily living (ADLs), pain, or pain catastrophizing scale preoperatively or 12-months postoperatively. Additionally, there was no difference in the median change between preoperative and postoperative ADL scores (P = .866), yet pain scores approached significance with a P value of .054. The pre-CMS transition group stayed significantly longer in the hospital postoperatively and was more commonly discharged to a skilled nursing facility. No difference was seen in 30-day readmission rates (P = .253). CONCLUSIONS: Results showed that patients had similar scores for ADL, quality of life, pain, and pain catastrophizing 12-months following their TKA. Movement of TKA from the Medicare inpatient only list did not have an immediate negative impact for patient reported outcomes and 30-day readmissions at our institution in the 6-month transition period.

Stool Interleukin-1ß Differentiates Clostridioides difficile Infection (CDI) From Asymptomatic Carriage and Non-CDI Diarrhea.

BACKGROUND: Despite advances in the understanding and diagnosis of Clostridioides difficile infection (CDI), clinical distinction within the colonization-infection continuum remains an unmet need. METHODS: By measuring stool cytokines and antitoxin antibodies in well-characterized cohorts of CDI (diarrhea, nucleic acid amplification test [NAAT] positive), non-CDI diarrhea (NCD; diarrhea, NAAT negative), asymptomatic carriers (ASC; no diarrhea, NAAT positive) and hospital controls (CON; no diarrhea, NAAT negative), we aim to discover novel biological markers to distinguish between these cohorts. We also explore the relationship of these stool cytokines and antitoxin antibody with stool toxin concentrations and disease severity. RESULTS: Stool interleukin (IL) 1ß, stool immunoglobulin A (IgA), and immunoglobulin G (IgG) anti-toxin A had higher (P < .0001) concentrations in CDI (n = 120) vs ASC (n = 43), whereas toxins A, B, and fecal calprotectin did not. Areas under the receiver operating characteristic curve (ROC-AUCs) for IL-1ß, IgA, and IgG anti-toxin A were 0.88, 0.83, and 0.83, respectively. A multipredictor model including IL-1ß and IgA anti-toxin A achieved an ROC-AUC of 0.93. Stool IL-1ß concentrations were higher in CDI compared to NCD (n = 75) (P < .0001) and NCD + ASC+ CON (CON, n = 75) (P < .0001), with ROC-AUCs of 0.83 and 0.86, respectively. Stool IL-1ß had positive correlations with toxins A (ρA = +0.55) and B (ρB = +0.49) in CDI (P < .0001) but not in ASC (P > .05). CONCLUSIONS: Stool concentrations of the inflammasome pathway, proinflammatory cytokine IL-1ß, can accurately differentiate CDI from asymptomatic carriage and NCD, making it a promising biomarker for CDI diagnosis. Significant positive correlations exist between stool toxins and stool IL-1ß in CDI but not in asymptomatic carriers.

Higher In Vivo Fecal Concentrations of Clostridioides difficile Toxins A and B in Patients With North American Pulsed-Field Gel Electrophoresis Type 1/Ribotype 027 Strain Infection.

Ultrasensitive, quantitative Clostridioides difficile stool toxin measurement demonstrated significantly higher concentrations of toxins A and B in patients infected with the North American pulsed-field gel electrophoresis type 1/ribotype 027 (NAP-1/027) strain compared with other strains, providing in vivo confirmation of the in vitro association between NAP-1/027 and elevated toxin production.

Ultrasensitive and Quantitative Toxin Measurement Correlates With Baseline Severity, Severe Outcomes, and Recurrence Among Hospitalized Patients With Clostridioides difficile Infection.

BACKGROUND: Stool toxin concentrations may impact Clostridioides difficile infection (CDI) severity and outcomes. We correlated fecal C difficile toxin concentrations, measured by an ultrasensitive and quantitative assay, with CDI baseline severity, attributable outcomes, and recurrence. METHODS: We enrolled 615 hospitalized adults (≥18 years) with CDI (acute diarrhea, positive stool nucleic acid amplification testing, and decision to treat). Baseline stool toxin A and B concentrations were measured by single molecule array. Subjects were classified by baseline CDI severity (4 scoring methods) and outcomes within 40 days (death, intensive care unit stay, colectomy, and recurrence). RESULTS: Among 615 patients (median, 68.0 years), in all scoring systems, subjects with severe baseline disease had higher stool toxin A+B concentrations than those without (P < .01). Nineteen subjects (3.1%) had a severe outcome primarily attributed to CDI (group 1). This group had higher median toxin A+B (14 303 pg/mL [interquartile range, 416.0, 141 967]) than subjects in whom CDI only contributed to the outcome (group 2, 163.2 pg/mL [0.0, 8423.3]), subjects with severe outcome unrelated to CDI (group 3, 158.6 pg/mL [0.0, 1795.2]), or no severe outcome (group 4, 209.5 pg/mL [0.0, 8566.3]) (P = .003). Group 1 was more likely to have detectable toxin (94.7%) than groups 2-4 (60.5%-66.1%) (P = .02). Individuals with recurrence had higher toxin A+B (2266.8 pg/mL [188.8, 29411]) than those without (154.0 pg/mL [0.0, 5864.3]) (P < .001) and higher rates of detectable toxin (85.7% versus 64.0%, P = .004). CONCLUSIONS: In CDI patients, ultrasensitive stool toxin detection and concentration correlated with severe baseline disease, severe CDI-attributable outcomes, and recurrence, confirming the contribution of toxin quantity to disease presentation and clinical course.

Fecal Mycobiota Combined With Host Immune Factors Distinguish Clostridioides difficile Infection From Asymptomatic Carriage.

BACKGROUND & AIMS: Although the role of gut microbiota in Clostridioides difficile infection (CDI) has been well established, little is known about the role of mycobiota in CDI. Here, we performed mycobiome data analysis in a well-characterized human cohort to evaluate the potential of using gut mycobiota features for CDI diagnosis. METHODS: Stool samples were collected from 118 hospital patients, divided into 3 groups: CDI (n = 58), asymptomatic carriers (Carrier, n = 28), and Control (n = 32). The nuclear ribosomal DNA internal transcribed spacer 2 was sequenced using the Illumina HiSeq platform to assess the fungal composition. Downstream statistical analyses (including Alpha diversity analysis, ordination analysis, differential abundance analysis, fungal correlation network analysis, and classification analysis) were then performed. RESULTS: Significant differences were observed in alpha and beta diversity between patients with CDI and Carrier (P < .05). Differential abundance analysis identified 2 genera (Cladosporium and Aspergillus) enriched in Carrier. The ratio of Ascomycota to Basidiomycota was dramatically higher in patients with CDI than in Carrier and Control (P < .05). Correlations between host immune factors and mycobiota features were weaker in patients with CDI than in Carrier. Using 4 fungal operational taxonomic units combined with 6 host immune markers in the random forest classifier can achieve very high performance (area under the curve ∼92.38%) in distinguishing patients with CDI from Carrier. CONCLUSIONS: Our study provides specific markers of stool fungi combined with host immune factors to distinguish patients with CDI from Carrier. It highlights the importance of gut mycobiome in CDI, which may have been underestimated. Further studies on the diagnostic applications and therapeutic potentials of these findings are warranted.

Absence of Toxemia in Clostridioides difficile Infection: Results from Ultrasensitive Toxin Assay of Serum.

Clostridioides difficile infection (CDI) is caused by Toxins A and B, secreted from pathogenic strains of C. difficle. This infection can vary greatly in symptom severity and in clinical presentation. Current assays used to diagnose CDI may lack the required sensitivity to detect the exotoxins circulating in blood. The ultrasensitive single molecule array (Simoa) assay was modified to separately detect toxin A and toxin B in serum with a limit of detection at the low picogram level. When applied to a diverse cohort, Simoa was unable to detect toxins A or B in serum from patients with CDI, including many classified as having severe disease. The detection of toxin may be limited by the inference of antitoxin antibodies circulating in serum. This result does not support the hypothesis that toxemia occurs in C. difficile infection, conflicting with the findings of other published reports.

Host Immune Markers Distinguish Clostridioides difficile Infection From Asymptomatic Carriage and Non-C. difficile Diarrhea.

BACKGROUND: Recent data indicate that Clostridioides difficile toxin concentrations in stool do not differentiate between C. difficile infection (CDI) and asymptomatic carriage. Thus, we lack a method to distinguish a symptomatic patient with CDI from a colonized patient with diarrhea from another cause. To address this, we evaluated markers of innate and adaptive immunity in adult inpatients with CDI (diagnosed per US guidelines), asymptomatic carriage, or non-CDI diarrhea. METHODS: CDI-NAAT patients had clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment. Carrier-NAAT patients had positive stool NAAT but no diarrhea. NAAT-negative patients (with and without diarrhea) were also enrolled. A panel of cytokines and anti-toxin A and B immunoglobulin (Ig) were measured in serum; calprotectin and anti-toxin B Ig A/G were measured in stool. NAAT-positive stool samples were tested by an ultrasensitive toxin assay (clinical cutoff, 20 pg/mL). RESULTS: Median values for interleukin (IL)-4, IL-6, IL-8, IL-10, IL-15, granulocyte colony-stimulating factor (GCSF), MCP-1, tumor necrosis factor α (TNF-α), and IgG anti-toxin A in blood and IgA/G anti-toxin B in stool were significantly higher in CDI patients compared with all other groups (P < .05). Concentration distributions for IL-6, GCSF, TNF-α, and IgG anti-toxin A in blood, as well as IgA and IgG anti-toxin B in stool, separated CDI patients from all other groups. CONCLUSIONS: Specific markers of innate and adaptive immunity distinguish CDI from all other groups, suggesting potential clinical utility for identifying which NAAT- and toxin-positive patients with diarrhea truly have CDI.

Laxative Use Does Not Preclude Diagnosis or Reduce Disease Severity in Clostridiodes difficile Infection.

BACKGROUND: To optimize utility of laboratory testing for Clostridiodes difficile infection (CDI), the 2017 Infectious Diseases Society of America-Society for Healthcare Epidemiology of America (IDSA-SHEA) clinical practice guidelines recommend excluding patients from stool testing for C. difficile if they have received laxatives within the preceding 48 hours. Sparse data support this recommendation. METHODS: Patients with new-onset diarrhea (≥3 bowel movements in any 24-hour period in the 48 hours before stool collection) and a positive stool C. difficile nucleic acid amplification test were enrolled. Laxative use within 48 hours before stool testing, severity of illness (defined by 4 distinct scoring methods), and clinical outcomes were recorded. RESULTS: 209 patients with CDI were studied, 65 of whom had received laxatives. There were no significant differences in the proportion of patients meeting severe CDI criteria by 4 severity scoring methods in patients receiving versus not receiving laxatives (66.2% vs 56.3%, respectively; P = .224) by IDSA-SHEA, the primary scoring system. Similar rates of serious outcomes attributable to CDI, including death, intensive care unit admission, and colectomy, were observed in the laxative and no laxative groups. CONCLUSIONS: Our study found similar rates of severe CDI and serious CDI-attributable clinical outcomes in CDI-diagnosed patients who did or did not receive laxatives. Precluding recent laxative users from CDI testing, as proposed by the IDSA-SHEA guideline, carries a potential for harm due to delayed diagnosis and treatment.

Mechanically stable rifampin antibiotic cement inhibits Pseudomonas aeruginosa biofilm surface growth.

Rifampin has been proven to be effective in the treatment of prosthetic infections due to its ability to intercalate into biofilms. The use of rifampin in antibiotic spacers is not well described, which would be especially important in the local periprosthetic environment where parenteral doses have poor penetration. The null hypothesis tests if rifampin use in polymethyl methacrylate (PMMA) cement will show no clinically significant impact on mechanical strength at antibiotic concentrations that remain bactericidal. Test antibiotic cement samples supplemented with 0, 30, 50, 100, 150, or 200 mg of rifampin into a standard 40 g bag were tested for compression to failure using published ASTM standards. The samples were then inoculated with Pseudomonas aeruginosa and either evaluated for lipopolysaccharide (LPS) presence as a marker of biofilm or tested by elution as the Kirby Bauer assay. Rifampin concentrations of 30 and 50 mg, showed no statistically different mechanical characteristics from control PMMA (p > 0.05). The 100-mg sample fell within the acceptable range of compressive strength and had significantly less LPS and bacterial presence compared to the control at 12 and 24 h. The ability of PMMA with 100 mg of rifampin to maintain its structural integrity and have significant bacterial inhibition at 12 and 24 h makes it a great candidate as an antibiotic bone cement additive. PMMA loaded with up to 100 mg of rifampin shows promise in the treatment and prevention of periprosthetic joint infection for total knee and total hip arthroplasty.

Evaluation of Patient Education Materials From Large-Language Artificial Intelligence Models on Carpal Tunnel Release.

BACKGROUND: ChatGPT, an artificial intelligence technology, has the potential to be a useful patient aid, though the accuracy and appropriateness of its responses and recommendations on common hand surgical pathologies and procedures must be understood. Comparing the sources referenced and characteristics of responses from ChatGPT and an established search engine (Google) on carpal tunnel surgery will allow for an understanding of the utility of ChatGPT for patient education. METHODS: A Google search of "carpal tunnel release surgery" was performed and "frequently asked questions (FAQs)" were recorded with their answer and source. ChatGPT was then asked to provide answers to the Google FAQs. The FAQs were compared, and answer content was compared using word count, readability analyses, and content source. RESULTS: There was 40% concordance among questions asked by the programs. Google answered each question with one source per answer, whereas ChatGPT's answers were created from two sources per answer. ChatGPT's answers were significantly longer than Google's and multiple readability analysis algorithms found ChatGPT responses to be statistically significantly more difficult to read and at a higher grade level than Google's. ChatGPT always recommended "contacting your surgeon." CONCLUSION: A comparison of ChatGPT's responses to Google's FAQ responses revealed that ChatGPT's answers were more in-depth, from multiple sources, and from a higher proportion of academic Web sites. However, ChatGPT answers were found to be more difficult to understand. Further study is needed to understand if the differences in the responses between programs correlate to a difference in patient comprehension.

Chronic obstructive pulmonary disease is an independent risk factor for increased opioid use in total hip arthroplasty: A retrospective PearlDiver study.

Background: Total hip arthroplasty (THA) has become an incredibly common procedure due to its' predictability and high success rate. The success of surgery is related to strict indications and careful optimization of medical comorbidities to decrease risk and improve outcomes. Chronic obstructive pulmonary disease (COPD) has been associated with increased medical and surgical complications. A regulatory focus on opioid utilization does not usually consider COPD as a risk factor, but limited research exists on the impact of COPD on outcomes and risks after THA. Methods: Retrospective all-inclusive database analysis of Medicare patients who had undergone THA between 2007 and 2017 included in the PearlDiver Database were studied. Postoperative opioid usage was examined at 1-, 3-, 6-, and 12 months, along with surgical infection, implant complications, and revisions. Post-operative complications within 30 days, either medical or implant related, were identified. Controlling for comorbidities, age, and sex, odds ratios were calculated using multivariable logistic regression with a significant α value of 0.05. Results: COPD patients had significantly higher rates of opioid usage postoperatively. COPD patients also had an increased rate of readmissions, medical/implant complications, and revision surgeries. Discussion: This is the only study raising concern regarding opioid use in COPD patients after total hip arthroplasty, which may be critical considering the associated respiratory depression further exacerbating the COPD. Considering the evidence of poor outcomes associated with COPD in arthroplasty, appropriately screening for COPD and counseling or planning for post-operative pain control and complications is paramount.

Preservation of the Innate Immune Response to Clostridioides difficile Infection in Hospitalized Immunocompromised Patients.

Background: Clostridioides difficile infection (CDI) immune response is influenced by the innate and adaptive (humoral) immune systems. Our prior research found attenuated humoral responses to C difficile in immunocompromised hosts (ICHs) with CDI. We sought to evaluate whether the innate immune response to CDI was influenced by ICH status. Methods: We conducted a prospective study of hospitalized adults with CDI (acute diarrhea, positive C difficile stool nucleic acid amplification testing [NAAT], and decision to treat), with and without immunosuppression and measured a panel of cytokines (granulocyte colony-stimulating factor [G-CSF], interleukin [IL]-10, IL-15, IL-1ß, IL-4, IL-6, IL-8, and tumor necrosis factor-α) in blood and stool at CDI diagnosis. Results were compared with measurements from a cohort of asymptomatic carrier patients (ASCs) (NAAT positive, without diarrhea) with and without immunocompromise. Results: One hundred twenty-three subjects (42 ICHs, 50 non-ICHs, 31 ASCs) were included. Median values for blood and stool cytokines were similar in ICH versus non-ICH CDI subjects. In blood, G-CSF, IL-10, IL-15, IL-6, and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). In stool, IL-1ß and IL-8 were higher in both groups of CDI subjects versus the ASC cohort (P < .05). Median stool concentrations of IL-1ß demonstrated significant differences between the groups (ICHs, 10.97 pg/mL; non-ICHs, 9.71 pg/mL; and ASCs, 0.56 pg/mL) (P < .0001). Conclusions: In this small exploratory analysis, ICH status did not significantly impact blood and fecal patterns of cytokines in humans at the diagnosis of CDI, suggesting that the innate immune response to C difficile may be conserved in immunocompromised patients.

The Case of Disappearing Tibia in Rheumatoid Knee Tenosynovitis.

Introduction: Knee pain and osteoarthritis are frequent patient complaints, with a rapidly increasing prevalence. By comparison, the prevalence of rheumatoid arthritis (RA) is significantly lower at around 1%. Inflammatory arthropathies, like RA, are difficult to differentiate from infection, crystal arthropathies, or malignancy. In addition, radiography and roentgenograms are often inconclusive or non-specific, making it much more difficult to evaluate, diagnose, and manage this condition. The current case is unique due to its location in the knee joint, rather than more common presentations in the upper extremities, and use of MRI imaging for diagnosis of RA with tenosynovitis. Case Report: In a Caucasian 70-year-old female with sudden debilitating knee pain and a large atraumatic defect over tibial plateau, MRI showed a large fluid collection within the left gracilis muscle. Gram stain and culture of the aspirate remained negative. The only significant history involved a possible diagnosis of RA. Conclusion: While rheumatoid tenosynovitis is common in the upper extremities, lower extremity features have not been well reported before. We diagnosed the patient with progressive RA and rheumatoid tenosynovitis. This unique presentation and rare usage of MRI imaging may be contributing to an underreporting of this diagnosis in the lower extremities.

Silver as an Antibiotic-Independent Antimicrobial: Review of Current Formulations and Clinical Relevance.

Background: The increase of multi-drug-resistant organisms has revived the use of silver as an alternative antibiotic-independent antimicrobial. Although silver's multimodal mechanism of action provides low risk for bacterial resistance, high local and uncontrolled concentrations have shown toxicity. This has resulted in efforts to develop novel silver formulations that are safer and more predictable in their application. Optimization of silver as an antimicrobial is crucial given the growing resistance profile against antibiotics. This article reviews formulations of silver used as antimicrobials, focusing on the mechanisms of action, potential for toxicity, and clinical applications. Methods: A search of four electronic databases (PubMed, Embase, MEDLINE, and Cochrane Library) was conducted for relevant studies up to January 2022. Searches were conducted for the following types of silver: ionic, nanoparticles, colloidal, silver nitrate, silver sulfadiazine, silver oxide, silver carboxylate, and AQUACEL® (ConvaTec, Berkshire, UK). Sources were compiled based on title and abstract and screened for inclusion based on relevance and study design. Results: A review of the antimicrobial activity and uses of ionic silver, silver nanoparticles, colloidal silver, silver nitrate, silver sulfadiazine, silver oxide, Aquacel, and silver carboxylate was conducted. The mechanisms of action, clinical uses, and potential for toxicity were studied, and general trends between earlier and more advanced formulations noted. Conclusions: Early forms of silver have more limited utility because of their uncontrolled release of silver ions and potential for systemic toxicity. Multiple new formulations show promise; however, there is a need for more prospective in vivo studies to validate the clinical potential of these formulations.

Silver carboxylate-doped titanium dioxide-polydimethylsiloxane coating decreases Cutibacterium acnes adherence and biofilm formation on polyether ether ketone.

BACKGROUND CONTEXT: Cutibacterium acnes (C. acnes) is a gram-positive facultative anaerobe found in the deep sebaceous follicles of the skin on the shoulder and back. C. acnes has been increasingly recognized as a pathogen in spinal surgical site infection (SSI) especially in the presence of instrumentation. PURPOSE: This study assesses whether a silver carboxylate-doped titanium dioxide-polydimethylsiloxane (TiO2-PDMS) coating can decrease C. acnes adherence and biofilm formation on PEEK and four other commonly used spinal implant materials, stainless steel, cobalt chromium, titanium, and titanium alloy. STUDY DESIGN: We compared the adherence of C. acnes over 24 hours between uncoated, 95:5 TiO2 to PDMS ratio with 10× silver carboxylate coating and a 100% silver carboxylate coating on each implant material, which were uniformly saw cut and sterilized. Implants were then subjected to scanning electron microscopy (SEM) and confocal scanning laser microscopy (CSLM). METHODS: Samples were coated using 95:5 TiO2-PDMS 10× silver carboxylate, 100% silver carboxylate, or left uncoated. C. acnes was applied onto the samples and allowed to adhere for periods of 4, 8, 12, 16, or 20 hours. Nonadherent bacteria were then washed from the samples. These samples were then allowed to continue incubating for a total of 24 hours. SEM and confocal laser scanning microscope were used to visualize all samples for the presence of biofilm and quantification of C. acnes adherence at each time point. RESULTS: The 95:5 TiO2-PDMS 10× silver carboxylate coating was able to significantly decrease C. acnes adherence on PEEK after 8, 12, 16, and 20 hours of adherence. No statistical difference was found between the 95:5 TiO2-PDMS 10× silver carboxylate coating and the 100% silver carboxylate positive control. We previously observed extensive C. acnes biofilm formation on uncoated PEEK, but none on PEEK coated with either the 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating . Furthermore, no biofilm formation was observed on stainless steel, cobalt chromium, titanium, and titanium alloy coated with 95:5 TiO2-PDMS 10× silver carboxylate or 100% Ag coating. CONCLUSION: A 95:5 TiO2-PDMS 10× silver carboxylate coating decreases C. acnes adhesion and prevents biofilm formation on PEEK and other common orthopedic implant materials. CLINICAL SIGNIFICANCE: A 95:5 TiO2-PDMS 10× silver carboxylate coating may help decrease spinal SSI due to C. acnes, especially in procedures with instrumentation.

In vitro visualization and quantitative characterization of Pseudomonas aeruginosa biofilm growth dynamics on polyether ether ketone.

Prevention and treatment of orthopedic device-related infection (ODRI) is complicated by the formation of bacterial biofilms. Biofilm formation involves dynamic production of macromolecules that contribute to the structure of the biofilm over time. Limitations to clinically relevant and translational biofilm visualization and measurement hamper advances in this area of research. In this paper, we present a multimodal methodology for improved characterization of Pseudomonas aeruginosa grown on polyether ether ketone (PEEK) as a model for ODRI. PEEK discs were inoculated with P. aeruginosa, incubated for 4-48 h time intervals, and fixed with 10% neutral-buffered formalin. Samples were stained with fluorescent dyes to measure biofilm components, imaged with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM), and quantified. We were able to visualize and quantify P. aeruginosa biofilm growth on PEEK implants over 48 h. Based on imaging data, we propose a generalized growth cycle that can inform orthopedic diagnostic and treatment for this pathogen on PEEK. These results demonstrate the potential of using a combined CLSM and SEM approach for determining biofilm structure, composition, post-adherence development on orthopedic materials. This model may be used for quantitative biofilm analysis for other pathogens and other materials of orthopedic relevance for translational study of ODRI.

Synergistic Effects of Silver Carboxylate and Chlorhexidine Gluconate for Wound Care and Prevention of Surgical Site Infections by Cutibacterium acnes and Methicillin-Resistant Staphylococcus aureus.

Background: This study presents the effectiveness of a combined silver carboxylate (AgCar) and chlorohexidine gluconate (AgCar:CHG) chemistry assessed against two commonly encountered nosocomial pathogens, Methicillin-resistant Staphylococcus aureus (MRSA) and Cutibacterium acnes, within the context of surgical antisepsis and wound care. Methods: Through an Institutional Review Board- and Institutional Animal Care and Use Committee (IACUC)-approved protocol, AgCar:CHG was applied to live Yucatan porcine skin and visualized by fast red and green staining to assess level of skin penetration. Dose response curves for Cutibacterium acnes and MRSA were generated to determine the optimal therapeutic ratio of AgCar to CHG. Coatings were applied to two different clinically available sutures and antimicrobial efficacy was evaluated at 24-hour intervals using Kirby-Bauer (KB) assays. Graphite furnace atomic absorption spectroscopy was used to measure AgCar elution from sutures over time. Results: Synergistic application of AgCar:CHG demonstrated deep pilosebaceous gland penetration on Yucatan pig skin. The therapeutic concentration range of AgCar was determined to be between 120 × -150 × and 30 × -60 × dopage for MRSA and Cutibacterium acnes, respectively. A 1:1 therapeutic ratio of AgCar to CHG was found to have 100% bactericidal activity against both pathogens. Sutures coated with AgCar:CHG showed sustained antimicrobial activity against MRSA and Cutibacterium acnes, and were significantly more efficacious than antimicrobial sutures over the three- to four-day period (p < 0.01). Conclusions: This AgCar:CHG chemistry demonstrates deep skin penetration, extended elution, and broad-spectrum antimicrobial activity compared with commercially available options. This chemistry shows promise as an additional tool for the prophylaxis of surgical site infections.

Pancreatic enzyme supplementation versus placebo for improvement of gastrointestinal symptoms in non-responsive celiac disease: A cross-over randomized controlled trial.

Background: Pancreatic Exocrine Insufficiency (PEI) is a possible cause of recurrent/persistent symptoms in celiac disease. Although pancreatic enzyme supplementation may be used to treat non-responsive celiac disease (NRCD) in clinical practice, clinical outcomes are variable and there is limited and low quality evidence to support this practice. The aim of this study was to assess the efficacy of pancreatic enzyme supplements (PES) for improvement of gastrointestinal symptoms in NRCD. Methods: Prospective, randomized, placebo-controlled, double-blind, cross-over trial in adults with NRCD examining Celiac Disease-Gastrointestinal Symptom Rating Scale (CeD-GSRS) scores on PES (pancrelipase co-administered with omeprazole) versus placebo (omeprazole only) during a 10-day treatment period. The study was registered under the clinical trials registry (https://clinicaltrials.gov/ number, NCT02475369) on 18 Jun 2015. Results: Twelve participants (nine female) were included in the per-protocol analysis; one participant had low fecal elastase-1. Pancrelipase was not associated with significant change in CeD-GSRS compared to placebo (-0.03 versus -0.26; P = 0.366). There was a significant decrease in mean values of total CeD-GSRS scores (3.58 versus 2.90, P = 0.004), abdominal pain (2.92 versus 2.42, P = 0.009), and diarrhea sub-scores (3.44 versus 2.92, P = 0.037) during the run-in period with omeprazole. Conclusion: In this prospective, cross-over randomized, placebo-controlled study, PES did not improve symptoms in patients with NRCD. It is unclear whether this is a trial effect or related to administration of omeprazole.

Silver Carboxylate-Eluting Titanium-Dioxide Polydimethylsiloxane Coating Inhibits Multi-Drug-Resistant Acinetobacterium baumannii and Vancomycin-Resistant Enterococcus faecalis Adherence and Proliferation on Orthopedic Trauma Fixation and Spinal Fusion Materials.

Background: Vancomycin-resistant Enterococcus faecalis and multi-drug-resistant (MDR) Acinetobacter baumannii are rising contributors to spinal fusion and fracture-associated infections (FAI), respectively. These MDR bacteria can form protective biofilms, complicating traditional antibiotic treatment. This study explores the effects of the antibiotic-independent antimicrobial silver carboxylate (AgCar)-doped coating on the adherence sand proliferation of these pathogens on orthopedic implant materials utilized in spinal fusion and orthopedic trauma fixation. Methods: Multi-drug-resistant Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis were inoculated on five common implant materials: cobalt chromium, titanium, titanium alloy, polyether ether ketone, and stainless steel. Dose response curves were generated to assess antimicrobial potency. Scanning electron microscopy and confocal laser scanning microscopy were utilized to characterize and quantify growth and adherence on each material. Results: The optimal AgCar concentration was a 95% titanium dioxide (TiO2)-5% polydimethylsiloxane (PDMS) matrix combined with 10 × silver carboxylate, which inhibited bacterial proliferation by 89.40% (p = 0.001) for MDR Acinetobacter baumannii and 84.02% (p = 0.001) for vancomycin-resistant Enterococcus faecalis compared with uncoated implants. A 95% TiO2-5% PDMS matrix combined with 10 × AgCar was equally effective at inhibiting bacterial proliferation across all implant materials for MDR Acinetobacter baumannii (p = 0.19) and vancomycin-resistant Enterococcus faecalis (p = 0.07). A 95% TiO2-5% PDMS matrix with 10 × AgCar is effective at decreasing bacterial adherence of both MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis on implant materials. Conclusions: Application of this antibiotic-independent coating for surgery in which these implant materials might be used may prevent adherence, biofilm formation, spinal infections, and FAI by MDR Acinetobacter baumannii and vancomycin-resistant Enterococcus faecalis.