Comparison of the effect of combined usage of povidone-iodine irrigation and topical vancomycin powder to the use of povidone-iodine irrigation alone on the periprosthetic joint infection incidence rate in patients undergoing primary total hip and knee arthroplasty: a protocol for multicenter prospective randomized clinical trial.

BACKGROUND: With the increasing number of joint replacement surgeries, periprosthetic joint infection (PJI) has become a significant concern in orthopedic practice, making research on PJI prevention paramount. Therefore, the study will aim to compare the effect of combined usage of povidone-iodine and topical vancomycin powder to the use of povidone-iodine alone on the PJI incidence rate in patients undergoing primary total hip (THA) and total knee arthroplasty (TKA). METHODS: The prospective randomized clinical trial will be conducted in two independent voivodeship hospitals with extensive experience in lower limb arthroplasties. The studied material will comprise 840 patients referred to hospitals for primary THA or TKA. The patients will be randomly allocated to two equal groups, receiving two different interventions during joint replacement. In group I, povidone-iodine irrigation and consecutively topical vancomycin powder will be used before wound closure. In group II, only povidone-iodine lavage irrigation will be used before wound closure. The primary outcome will be the incidence rate of PJI based on the number of patients with PJI occurrence within 90 days after arthroplasty. The occurrence will be determined using a combined approach, including reviewing hospital records for readmissions and follow-up phone interviews with patients. The infection will be diagnosed based on Musculoskeletal Infection Society criteria. The chi-square test will be used to compare the infection rates between the two studied groups. Risk and odds ratios for the between-groups comparison purposes will also be estimated. Medical cost analysis will also be performed. DISCUSSION: A randomized clinical trial comparing the effect of combined usage of povidone-iodine irrigation and vancomycin powder to the use of povidone-iodine irrigation alone in preventing PJIs after primary arthroplasty is crucial to advancing knowledge in orthopedic surgery, improving patient outcomes, and guiding evidence-based clinical practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT05972603 . Registered on 2 August 2023.

An effective antibiofilm strategy based on bacteriophages armed with silver nanoparticles.

The emerging antibiotic resistance in pathogenic bacteria is a key problem in modern medicine that has led to a search for novel therapeutic strategies. A potential approach for managing such bacteria involves the use of their natural killers, namely lytic bacteriophages. Another effective method involves the use of metal nanoparticles with antimicrobial properties. However, the use of lytic phages armed with nanoparticles as an effective antimicrobial strategy, particularly with respect to biofilms, remains unexplored. Here, we show that T7 phages armed with silver nanoparticles exhibit greater efficacy in terms of controlling bacterial biofilm, compared with phages or nanoparticles alone. We initially identified a novel silver nanoparticle-binding peptide, then constructed T7 phages that successfully displayed the peptide on the outer surface of the viral head. These recombinant, AgNP-binding phages could effectively eradicate bacterial biofilm, even when used at low concentrations. Additionally, when used at concentrations that could eradicate bacterial biofilm, T7 phages armed with silver nanoparticles were not toxic to eukaryotic cells. Our results show that the novel combination of lytic phages with phage-bound silver nanoparticles is an effective, synergistic and safe strategy for the treatment of bacterial biofilms.

Prospective, Long-Term Functional Outcomes of Extra-Osseous Talotarsal Stabilization (EOTTS) Using HyProCure in Adult Patients with Talotarsal Joint Instability: Assessment of Physical Activity and Patient Satisfaction.

BACKGROUND: The partial dislocation of the talus from the calcaneus and navicular bones is a primary factor leading to a prolonged overpronation during weightbearing. This study aimed to assess the possibility of returning to physical activity and long-term patient satisfaction after an extra-osseous talotarsal stabilization (EOTTS) procedure with a HyProCure sinus tarsi implant for partial talotarsal joint dislocation (TTJ). METHODS: A total of 41 adult patients (61 feet), with an average age of 46.41, were included and treated surgically with EOTTS as a stand-alone surgery. Physical activity and functional scores were assessed pre- and post-operatively using questionnaires-the UCLA Activity Score, Symptom-Related Ankle Activity Scale (SAAS), Sports Frequency Score (SFS), Lower Extremity Functional Scale (LEFS), and VAS scale. Satisfaction was assessed on a ten-point scale. The follow-up period was on average 8.61 years (from 7.33 to 10.31). RESULTS: EOTTS had a positive impact on physical activity, and a high rate of patient satisfaction (8.95 ± 1.9) was noted. The treatment led to a reduction in foot pain, as well as an increase in SAAS and LEFS scores (15,6% and 19,3%, respectively, p <0.01). The VAS pain score decreased by 18,6% (p <0.001). SFS and UCLA scores showed a small increase, but it was not statistically significant. A positive correlation was noted between patient satisfaction and time of physical activity per week (R = 0.33, p =0.04), and also between patient satisfaction and SAAS scores (R = 0.43, p =0.005). Pain from other joints (knee, hip) was eliminated or reduced in 40% of patients after surgery. CONCLUSIONS: EOTTS with a HyProCure implant is an effective long-term treatment option for partial talotarsal joint dislocation, leading to a reduction in foot pain and increased patient satisfaction, and allowing for a return to physical activity.

δ-Lactones-A New Class of Compounds That Are Toxic to E. coli K12 and R2-R4 Strains.

Lactones are among the well-known organic substances with a specific taste and smell. They are characterized by antibacterial, antiviral, anti-inflammatory, and anti-cancer properties. In recent years, among this group of compounds, new biologically active substances have been searched by modifying the main (leading) structure with new analogs with stronger or different responses that may have a toxic effect on the cells of pathogenic bacteria and constitute an alternative to commonly used antibiotics. A preliminary study of δ-lactone derivatives as new potential candidates for antibacterial drugs was conducted. Particular emphasis was placed on the selection of the structure of lactones with the highest biological activity, especially those with fluorine in their structure as a substituent in terms of action on bacterial lipopolysaccharide (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2-R4 (LPS of different lengths in its structure). In the presented studies, on the basis of the conducted MIC and MBC tests, it was shown that the antibacterial (toxic) activity of lactones depends on their structure and the length of the bacterial LPS in the membrane of specific strains. Moreover, oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylase was analyzed. The analyzed damage values were compared with the modification with appropriate antibiotics: ciprofloxacin, bleomycin, and cloxacillin. The presented research clearly shows that lactone derivatives can be potential candidates as substitutes for drugs, e.g., the analyzed antibiotics. Their chemical and biological activity is related to coumarin derivatives and the corresponding δ-lactone groups in the structure of the substituent. The observed results are of particular importance in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of a microbial pandemic.

1,2-Diarylethanols-A New Class of Compounds That Are Toxic to E. coli K12, R2-R4 Strains.

An initial study of 1,2-diarylethanols derivatives as new potential antibacterial drugs candidates was conducted. Particular emphasis was placed on the selection of the structure of 1,2-diarylethanols with the highest biological activity of lipopolysaccharides (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2-R4 (with different lengths of LPS in its structure). In the presented studies, based on the conducted minimum inhibitory concentration (MIC) and MBC tests, it was demonstrated that the antibacterial (toxic) effect of 1,2-diarylethanols depends on their structure and the length of LPS bacteria in the membrane of specific strains. Moreover, the oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylases was analysed. The analysed damage values were compared with modification with appropriate antibiotics; bacterial DNA after the use of kanamycin, streptomycin, ciprofloxacin, bleomycin and cloxicillin. The presented research clearly shows that 1,2-diarylethanol derivatives can be used as potential candidates for substitutes for new drugs, e.g., the analysed antibiotics. Their chemical and biological activity is related to two aromatic groups and the corresponding chemical groups in the structure of the substituent. The observed results are particularly important in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of pandemics caused by microorganisms.

All That Glitters Is Not Silver-A New Look at Microbiological and Medical Applications of Silver Nanoparticles.

Silver and its nanoparticles (AgNPs) have different faces, providing different applications. In recent years, the number of positive nanosilver applications has increased substantially. It has been proven that AgNPs inhibit the growth and survival of bacteria, including human and animal pathogens, as well as fungi, protozoa and arthropods. Silver nanoparticles are known from their antiviral and anti-cancer properties; however, they are also very popular in medical and pharmaceutical nanoengineering as carriers for precise delivery of therapeutic compounds, in the diagnostics of different diseases and in optics and chemistry, where they act as sensors, conductors and substrates for various syntheses. The activity of AgNPs has not been fully discovered; therefore, we need interdisciplinary research to fulfil this knowledge. New forms of products with silver will certainly find application in the future treatment of many complicated and difficult to treat diseases. There is still a lack of appropriate and precise legal condition regarding the circulation of nanomaterials and the rules governing their safety use. The relatively low toxicity, relative biocompatibility and selectivity of nanoparticle interaction combined with the unusual biological properties allow their use in animal production as well as in bioengineering and medicine. Despite a quite big knowledge on this topic, there is still a need to organize the data on AgNPs in relation to specific microorganisms such as bacteria, viruses or fungi. We decided to put this knowledge together and try to show positive and negative effects on prokaryotic and eukaryotic cells.

Coumarin Derivatives as New Toxic Compounds to Selected K12, R1-R4 E. coli Strains.

Coumarins are natural compounds that were detected in 80 species of plants. They have numerous applications including the medical, food, tobacco, perfumery, and spirit industries. They show anti-swelling and diastolic effects. However, excess consumption of coumarins may adversely affect our health, because they are easily absorbed from the intestines into the lymph and blood, causing cirrhosis of the liver. Peptidomimetics are molecules whose structure and function are similar to those of peptides. They are an important group of compounds with biological, microbiological, anti-inflammatory, and anti-cancer properties. Therefore, studies on new peptidomimetics, which load the effect of native peptides, whose half-life in the body is much longer due to structural modifications, are extremely important. A preliminary study of coumarin analogues and its derivatives as new potential antimicrobial drugs containing carboxylic acid or ester was performed to determine their basic structure related to their biological features against various types of Gram-stained bacteria by lipopolysaccharide (LPS). We hypothesized that the toxicity (antibacterial activity) of coumarin derivatives is dependent on the of LPS in bacteria and nature and position of the substituent which may be carboxylic acid, hydroxyl groups, or esters. In order to verify this hypothesis, we used K12 (smooth) and R1-R4 (rough) Escherichia coli strains which are characterized by differences in the type of LPS, especially in the O-antigen region, the outermost LPS layer. In our work, we synthesized 17 peptidomimetics containing a coumarin scaffold and checked their influence on K12 and R1-R4 E. coli strains possessing smooth and rough LPS. We also measured the damage of plasmid DNA caused by target compounds. The results of our studies clearly support the conclusion that coumarin peptidomimetics are antagonistic compounds to many of the currently used antibiotics. The high biological activity of the selected coumarin peptidomimetic was associated with identification of the so-called magic methyl groups, which substantially change the biochemical properties of target compounds. Investigating the effects of these compounds is particularly important in the era of increasingly common resistance in bacteria.

Biological reconstruction of large osteochondral lesions of the talar dome with a modified "sandwich" technique-Midterm results.

BACKGROUND: Surgical treatment for large osteochondral lesions of the talar dome (OLTD) must restore the convexity and curvature of the talus. Here, we present midterm results and describe the modified "sandwich" reconstruction procedure. Bone defects were restored using a biological inlay consists of autologous bone chips that were mixed with bone marrow concentrate and fibrin glue and covered with a xenogeneic collagen membrane infiltrated with bone marrow concentrate and stabilized by fibrin glue. METHODS: Ten patients who were treated using a modified "sandwich" OLTD reconstruction were assessed after an average follow-up period of 46.4 (±18) months, using the clinical American Orthopaedic Foot and Ankle Society Ankle Hindfoot Scale (AOFAS) score and radiological magnetic resonance observation of cartilage repair tissue (MOCART) score. RESULTS: The mean AOFAS score increased significantly from 58.3 (±8.5) points to 81.8 (±15.5) points as well the mean VAS score reduced significantly from 5.58 (±0.97) to 1.83 (±0.93) points. The average MOCART score was 69.5% (±16.7%) in the final follow-up. CONCLUSIONS: The presented modified "sandwich" technique permanently recreates the convexity and curvature in large osteochondral lesions of the talar dome with a single step surgical procedure.