ABSTRACT
Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.
Subject(s)
Brain Neoplasms , Cancer Vaccines , Glioblastoma , Precision Medicine , Vaccines, Subunit , Humans , Glioblastoma/immunology , Glioblastoma/therapy , Female , Vaccines, Subunit/immunology , Vaccines, Subunit/therapeutic use , Cancer Vaccines/immunology , Cancer Vaccines/therapeutic use , Cancer Vaccines/administration & dosage , Male , Middle Aged , Precision Medicine/methods , Aged , Adult , Brain Neoplasms/immunology , Brain Neoplasms/therapy , Antigens, Neoplasm/immunology , T-Lymphocytes/immunology , Treatment Outcome , Protein Subunit VaccinesABSTRACT
The widespread prevalence of periprosthetic joint infections (PJIs) poses significant challenges in orthopedic surgeries, with pathogens such as Staphylococcus epidermidis being particularly problematic due to their capability to form biofilms on implants. This study investigates the efficacy of an innovative silver nitrate-embedded poly-L-lactide biopolymer coating designed to prevent such infections. The methods involved applying varying concentrations of silver nitrate to in vitro setups and recording the resultant bacterial growth inhibition across different serum environments, including human serum and various animal sera. Results highlighted a consistent and significant inhibition of S. epidermidis growth at all tested concentrations in each type of serum without adverse interactions with serum proteins, which commonly compromise antimicrobial efficacy. This study concludes that the silver nitrate-embedded biopolymer coating exhibits potent antibacterial properties and has potential for use in clinical settings to reduce the incidence of PJIs. Furthermore, the findings underscore the importance of considering serum interactions in the design and testing of antimicrobial implants to ensure their effectiveness in actual use scenarios. These promising results pave the way for further research to validate and refine this technology for clinical application, focusing on optimizing silver ion release and assessing biocompatibility in vivo.
ABSTRACT
Artificial insemination (AI) centres select bulls as calves according to their genetic breeding values and raise them until the first semen collection; yet, a high dropout rate of reared bulls is a problem for AI centres. Potential hormonal indicators of bull sexual maturation (cortisol, dehydroepiandrosterone (DHEA), testosterone, oestradiol, insulin-like growth factor 1 (IGF-1)) were observed and evaluated in relation to the performance parameters to perhaps identify candidate biomarkers allowing an early selection of bulls as suitable sires. Blood samples from 102 German Holstein calves at 4 ± 1, 8 ± 1 and 12 ± 2 months of age from six AI centres were analysed using validated immunoassays for cortisol, DHEA, testosterone, oestradiol and IGF-1. Semen analyses included native and thawed diluted semen. Bulls were classified at the first semen collection into groups with good versus poor performance (GP vs. LP). After 2 years, the subsequent differentiation was done in high (HPP), medium (MPP) and low performance persistency (LPP). Age at first semen collection was an important factor for sperm quality. Cortisol concentrations decreased with age, but the cortisol/DHEA ratio decreased with age only in GP bulls (p < .05). Oestradiol and testosterone concentrations both correlated with libido behaviour (p < .05). Testosterone and IGF-1 concentrations were higher at the time of first semen collection in GP bulls and increased with age (p < .05). In conclusion, testosterone and IGF-1 concentrations at first semen collection are associated with performance at first semen collection and future performance persistency, and might be useful early biomarkers for consistent sperm producing bulls on AI centres.
Subject(s)
Biomarkers , Estradiol , Insemination, Artificial , Semen Analysis , Animals , Male , Cattle/physiology , Insemination, Artificial/veterinary , Biomarkers/blood , Semen Analysis/veterinary , Estradiol/blood , Testosterone/blood , Insulin-Like Growth Factor I/analysis , Insulin-Like Growth Factor I/metabolism , Hydrocortisone/blood , Sexual Maturation/physiology , Semen , Dehydroepiandrosterone/bloodABSTRACT
Efficient management of pig reproduction is paramount for the sustainability and productivity of the global pork industry. Modern artificial insemination (AI) breeding programs have greatly benefited from the integration of advanced selection methods and biomarkers to enhance the reproductive performance of boars. While traditional selection methods have relied soley on boar phenotype, such as growth rate and conformation, modern pig breeding has shifted more and more toward molecular and genetic tools, which are still complemented by phenotypic traits. These methods encompass genomics, transcriptomics, and proteomics. Biomarkers serve as critical indicators of boar reproductive capacity. They can help to identify individuals with superior fertility and aid in the early identification of potential fertility issues, allowing for proactive management strategies. This review summarizes current knowledge of various biomarkers associated with semen quality, sperm function, and overall reproductive fitness in boars. Furthermore, we explore advanced technologies and their potential applications in uncovering novel selection methods and biomarkers for predicting boar fertility. A comprehensive understanding of selection criteria and biomarkers governing boar reproductive capacity is essential for developing effective breeding programs to enhance swine reproductive performance.
ABSTRACT
Feeding of breeding boars in artificial insemination (AI) centers is critical to maintaining and improving breeding quality and performance in agriculture. Modern feeding strategies for AI boars are aiming towards maximizing their lifetime semen dose output. Given the high growth potential of modern swine genetics, AI boars should be controlled in their daily gain to reduce stress factors for the locomotion system, final body weights, and improve their survivability but also the ease of handling boars. The feeding program should be designed in such a way that young boars (up to 7 months of age) are limited to a daily gain of 400-600â¯g. Mature boars should be fed towards a body condition score of '2'. Aside from energy intake, protein sources should provide 0.62% SID lysine. As far as minerals and vitamins, special attention should be given to Calcium and Phosphorus as they play a crucial role in bone mineralization. A standardized total tract digestible Calcium-Phosphorus ratio between 1.75:1 and 1.82:1 seems to be most favorable. While certain nutritional requirements are needed to enable the production of ejaculates eligible for AI, considerations should be given to the mitigation of risk factors like mycotoxins, herbicides, and pesticides. Most feed additives and supplements lack consistency in their effect across studies evaluated in this review.
ABSTRACT
The swine gastrointestinal tract contains a great variety of microbes, forming a complex and dynamic ecosystem. Various internal and external factors (e.g. age, breed and diet) may influence its composition. This study aimed to investigate the gut microbial diversity of German Piétrain boars housed on different deep-litter bedding materials (regional wood shavings, linen, hemp, spelt husks, and wood shavings) via 16S-rDNA sequencing. Additionally, short-chain fatty acids were analysed using gas chromatography. Fresh faecal samples (n = 80) from 40 Piétrain boars were collected twice during the trial. Although it can be assumed that boars ingest bedding orally, no differences in the microbiome composition could be found. The main phyla were Firmicutes and Bacteroides. Acinetobacter was identified as a biomarker for sperm quality differences (total sperm motility) in breeding boars.
Subject(s)
Acinetobacter , Feces , Housing, Animal , Sperm Motility , Animals , Male , Feces/microbiology , Acinetobacter/isolation & purification , Gastrointestinal Microbiome , Sus scrofa , Fatty Acids, Volatile/analysis , RNA, Ribosomal, 16S/analysis , Floors and Floorcoverings , SwineABSTRACT
Periprosthetic joint infection is a feared complication after the megaprosthetic reconstruction of oncologic and non-oncologic bone defects of including the knee or hip joint. Due to the relative rarity of these procedures, however, optimal management is debatable. Considering the expanding use of megaprostheses in revision arthroplasty and the high revision burden in orthopedic oncology, the risk of PJI is likely to increase over the coming years. In this non-systematic review article, we present and discuss current management options and the associated results focusing on studies from the last 15 years and studies from dedicated centers or study groups. The indication, surgical details and results in controlling infection are presented for debridement, antibiotics, irrigation and retention (DAIR) procedure with an exchange of the modular components, single-stage implant exchange, two-stage exchanges and ablative procedures.
Subject(s)
Debridement , Prosthesis-Related Infections , Humans , Prosthesis-Related Infections/surgery , Debridement/methods , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Reoperation/methods , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Knee Prosthesis/adverse effects , Hip Prosthesis/adverse effects , Therapeutic Irrigation/methodsABSTRACT
Ovarian cancer is one of the most common cancers among women and the most lethal malignancy of all gynecological cancers. Surgery is promising in the early stages; however, most patients are first diagnosed in the advanced stages, where treatment options are limited. Here, we present a 49-year-old patient who was first diagnosed with stage III ovarian cancer. After the tumor progressed several times under guideline therapies with no more treatment options available at that time, the patient received a fully individualized neoantigen-derived peptide vaccine in the setting of an individual healing attempt. The tumor was analyzed for somatic mutations via whole exome sequencing and potential neoepitopes were vaccinated over a period of 50 months. During vaccination, the patient additionally received anti-PD-1 therapy to prevent further disease progression. Vaccine-induced T-cell responses were detected using intracellular cytokine staining. After eleven days of in vitro expansion, four T-cell activation markers (namely IFN-É£, TNF-α, IL-2, and CD154) were measured. The proliferation capacity of neoantigen-specific T-cells was determined using a CFSE proliferation assay. Immune monitoring revealed a very strong CD4+ T-cell response against one of the vaccinated peptides. The vaccine-induced T-cells simultaneously expressed CD154, TNF, IL-2, and IFN-É£ and showed a strong proliferation capacity upon neoantigen stimulation. Next-generation sequencing, as well as immunohistochemical analysis, revealed a loss of Beta-2 microglobulin (B2M), which is essential for MHC class I presentation. The results presented here implicate that the application of neoantigen-derived peptide vaccines might be considered for those cancer stages, where promising therapeutic options are lacking. Furthermore, we provide more data that endorse the intensive investigation of B2M loss as a tumor escape mechanism in clinical trials using anti-cancer vaccines together with immune-checkpoint inhibitors.
ABSTRACT
Since artificial insemination is common practice in pig breeding, the quality and persistence of the semen are decisive for the usability of individual boars. In the current study, genome-wide association analyses were performed to investigate the genetic variability underlying phenotypic variations in semen characteristics. These traits comprise sperm morphology and sperm motility under different temporal and thermal storage conditions, in addition to standard semen quality parameters. Two consecutive samples of the fourth and fifth ejaculates from the same boar were comprehensively analyzed in a genotyped Piétrain boar population. A total of 13 genomic regions on different chromosomes were identified that contain single-nucleotide polymorphisms significantly associated with these traits. Subsequent analysis of the genomic regions revealed candidate genes described to be involved in spermatogenesis, such as FOXL3, GPER1, PDGFA, PRKAR1B, SNRK, SUN1, and TSPO, and sperm motility, including ARRDC4, CEP78, DNAAF5, and GPER1. Some of these genes were also associated with male fertility or infertility in mammals (e.g., CEP78, GPER1). The analyses based on these laboriously determined and valuable phenotypes contribute to a better understanding of the genetic background of male fertility traits in pigs and could prospectively contribute to the improvement of sperm quality through breeding approaches.
Subject(s)
Semen Analysis , Semen , Swine/genetics , Male , Animals , Genome-Wide Association Study , Sperm Motility/genetics , Spermatozoa , MammalsABSTRACT
Poly-L-lactic acid (PLLA) implants have been used for bone fixation for decades. However, upon insertion, they can cause a foreign body reaction (FBR) that may lead to complications. On 15 December 2023, a systematic review was conducted to search for articles on the PubMed, MeSH term, and Scopus databases using the keywords 'PLLA' and 'foreign body reaction'. The articles were reviewed not only for the question of FBR, its severity, and the manifestation of symptoms but also for the type of implant and its location in the body, the species, and the number of individuals included. A total of 71 original articles were identified. Of these, two-thirds reported on in vivo trials, and one-third reported on clinical applications. The overall majority of the reactions were mild in more than half of the investigations. Symptoms of extreme and extensive FBR mainly include osteolysis, ganglion cysts, and swelling. The localization of PLLA implants in bone can often result in osteolysis due to local acidosis. This issue can be mitigated by adding hydroxyapatite. There should be no strong FBR when PLLA is fragmented to 0.5-4 µm by extracorporeal shock wave.
ABSTRACT
BACKGROUND: The responsible use of 3D-printing in medicine includes a context-based quality assurance. Considerable literature has been published in this field, yet the quality of assessment varies widely. The limited discriminatory power of some assessment methods challenges the comparison of results. The total error for patient specific anatomical models comprises relevant partial errors of the production process: segmentation error (SegE), digital editing error (DEE), printing error (PrE). The present review provides an overview to improve the general understanding of the process specific errors, quantitative analysis, and standardized terminology. METHODS: This review focuses on literature on quality assurance of patient-specific anatomical models in terms of geometric accuracy published before December 4th, 2022 (n = 139). In an attempt to organize the literature, the publications are assigned to comparable categories and the absolute values of the maximum mean deviation (AMMD) per publication are determined therein. RESULTS: The three major examined types of original structures are teeth or jaw (n = 52), skull bones without jaw (n = 17) and heart with coronary arteries (n = 16). VPP (vat photopolymerization) is the most frequently employed basic 3D-printing technology (n = 112 experiments). The median values of AMMD (AMMD: The metric AMMD is defined as the largest linear deviation, based on an average value from at least two individual measurements.) are 0.8 mm for the SegE, 0.26 mm for the PrE and 0.825 mm for the total error. No average values are found for the DEE. CONCLUSION: The total error is not significantly higher than the partial errors which may compensate each other. Consequently SegE, DEE and PrE should be analyzed individually to describe the result quality as their sum according to rules of error propagation. Current methods for quality assurance of the segmentation are often either realistic and accurate or resource efficient. Future research should focus on implementing models for cost effective evaluations with high accuracy and realism. Our system of categorization may be enhancing the understanding of the overall process and a valuable contribution to the structural design and reporting of future experiments. It can be used to educate specialists for risk assessment and process validation within the additive manufacturing industry.
ABSTRACT
INTRODUCTION: We investigated the time to reimplantation (TTR) during two-stage revision using static spacers with regard to treatment success and function in patients with chronic periprosthetic joint infection (PJI) of the knee. METHODS: 163 patients (median age 72 years, 72 women) who underwent two-stage exchange for chronic knee PJI between 2012 and 2020 were retrospectively analyzed (based on the 2011 Musculoskeletal Infection Society criteria). A cutoff TTR for increased risk of reinfection was identified using the maximally selected log-rank statistic. Infection control, aseptic revisions and overall survival were analyzed using Kaplan-Meier survival estimates. Adjustment for confounding factors-the Charlson Comorbidity Index (CCI) and C-reactive protein (CRP)-was done with a Cox proportional hazards model. RESULTS: When TTR exceeded 94 days, the adjusted hazard of reinfection was increased 2.8-fold (95% CI 1.4-5.7; p = 0.0036). The reinfection-free rate was 67% (95% CI 52-79%) after 2 years and 33% (95% CI 11-57%) after 5 years for a longer TTR compared to 89% (95% CI 81-94%) and 80% (95% CI 69-87%) at 2 and 5 years, respectively, for a shorter TTR. Adjusted overall survival and number of aseptic revisions did not differ between the longer TTR and shorter TTR groups. Maximum knee flexion was 90° (IQR 84-100) for a longer TTR and 95° (IQR 90-100) for a shorter TTR (p = 0.0431), with no difference between the groups in Oxford Knee Score. Baseline characteristics were similar (body mass index, age, previous surgeries, microorganisms) for the two groups, except that there was a higher CCI (median 4 vs. 3) and higher CRP (median 3.7 vs 2.6 mg/dl) in the longer TTR group. CONCLUSION: A long TTR is sometimes unavoidable in clinical practice, but surgeons should be aware of a potentially higher risk of reinfection. LEVEL OF EVIDENCE: III, retrospective comparative study.
Subject(s)
Arthritis, Infectious , Arthroplasty, Replacement, Knee , Knee Prosthesis , Prosthesis-Related Infections , Humans , Female , Aged , Arthroplasty, Replacement, Knee/adverse effects , Retrospective Studies , Reinfection/complications , Knee Joint/surgery , Risk Factors , Treatment Outcome , C-Reactive Protein , Reoperation , Replantation/adverse effects , Arthritis, Infectious/complications , Prosthesis-Related Infections/etiology , Prosthesis-Related Infections/surgery , Knee Prosthesis/adverse effectsABSTRACT
Aims: Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model. Methods: Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST). Results: Greater bacterial burden in the early group compared to the delayed and control groups at revision surgery indicates a retraction of the infection from one to four weeks. Infection was cleared in all animals in the early and delayed groups at euthanasia, but not in the control group. Osteotomies healed in the early group, but bone healing was significantly compromised in the delayed and control groups. Conclusion: The duration of the infection from one to four weeks does not impact the success of infection clearance in this model. Bone healing, however, is impaired as the duration of the infection increases.
ABSTRACT
Artificial insemination (AI) with liquid-preserved stallion semen is a widely used reproductive technology. As the demand for AI doses of high-class stallions is transnational, they are frequently exposed to long-distance transport. Since recent studies in boars indicated that vibration emissions caused by transport negatively affected sperm quality in vitro, this study questioned whether sperm quality in stallions is similarly impaired. Furthermore, we investigated stallion and extender-related differences in the spermatozoa's resistance to transport-related quality loss. Stallion ejaculates (n = 30) were collected at a German AI center, split in half, and subsequently diluted to a final sperm concentration of 50 × 106 sperm/mL using the semen extenders EquiPlus or Gent (both Minitüb GmbH, Germany). Four 12 mL aliquots of each sample were filled in plastic syringes according to a split-sample design and exposed to vibration (Displacement index Di = 3.0 ± 0.1) at 5 °C for 0 h (control), 3 h, 6 h or 9 h. All samples were stored for four days at 5 °C after transport simulation and analyzed for total sperm motility, thermo-resistance, membrane integrity, and mitochondrial activity determined by flow cytometry as well as the pH. After calculating generalized linear mixed models for each sperm quality trait, a negative impact of the duration of transport simulation could be shown on total sperm motility (P = 0.001), thermo-resistance (P = 0.030), and the pH (P = 0.001). Simulated transport for 6 h and 9 h diminished sperm quality (P ≤ 0.01), with 9 h reducing thermo-resistance by 5 ± 2.2% points (PP) for EquiPlus and sperm motility by 2.2 ± 1.7 PP for Gent compared to the control group. In contrast, samples exposed to vibration for 3 h showed no decline in sperm quality (P > 0.05). The individual stallion influenced every semen trait (P < 0.05) and transport-related losses in sperm thermo-resistance of up to 15.9 PP were demonstrated. Furthermore, EquiPlus was superior to Gent in all semen assessments (P < 0.001). We conclude that in vitro sperm quality is impaired by vibration. As the quality loss depends on the transport time, we recommend keeping shipping time as short as possible especially for spermatozoa of stallions that are susceptible to vibration-induced sperm quality loss.
Subject(s)
Semen Preservation , Semen , Horses , Male , Animals , Swine , Sperm Motility , Semen Preservation/veterinary , Vibration , Spermatozoa , Insemination, Artificial/veterinaryABSTRACT
Transport-related vibrations (TV) compromise the quality of conventionally stored (17 °C) boar semen, but knowledge about TV effects after 5 °C transport is insufficient. This study evaluates the effects of TV after novel 5 °C transport compared to a 17 °C control. Ejaculates of 18 fertile Piétrain boars, diluted in a split sample procedure using Androstar Premium® (AP, 5 °C storage) or Beltsville Thawing Solution (BTS, 17 °C storage), were subjected to transport simulation using a laboratory shaker IKA MTS 4. The timing was set according to the respective processing protocols: for 17 °C BTS samples, TV simulation was performed the day of collection, 5 °C AP samples were subjected to TV the day after collection following completion of the established cooling curve to 5 °C. Six samples per ejaculate were exposed to different TV durations (0 h, 3 h, or 6 h) to evaluate the effect on sperm quality (progressive motility (PM), thermo-resistance test (30 and 300 min incubation at 38 °C (TRT30/TRT300)), mitochondrial activity (MITO), plasma membrane and acrosome integrity (PMAI)). Generalized linear mixed models revealed TV (P = 0.021) and storage time (P < 0.001) dependent declines in PM. Direct, pairwise comparisons revealed that 5 °C samples are not affected by TV (P(3 h vs. 6 h transport) = 1.0; P(0 h vs. 6 h transport) = 1.0). They therefore showed superior quality maintenance after TV compared to 17 °C samples (P(3 h vs. 6 h transport) = 0.025; P(0 h vs. 6 h transport) < 0.001). Concluding, low-temperature transport is possible without significant semen quality loss and with better quality maintenance than standard transport.
Subject(s)
Semen Preservation , Semen , Swine , Male , Animals , Semen/metabolism , Semen Analysis/veterinary , Temperature , Vibration , Semen Preservation/veterinary , Semen Preservation/methods , Sperm Motility , SpermatozoaABSTRACT
Next-generation sequencing (NGS)-based comprehensive tumor profiling from liquid biopsy samples can significantly improve diagnosis and monitoring of tumors when high-quality tissue material is difficult to obtain. In addition, it offers the potential to capture the entire complexity of the tumor, which is particularly important for highly heterogeneous or metastatic tumors. Here, we report the findings of an analytical performance evaluation of the TruSight Oncology 500 circulating tumor DNA (ctDNA) assay, a 523-gene NGS panel developed for ctDNA-based comprehensive genomic profiling of tumors, using reference and patient samples. Using 30 ng cell-free DNA, the assay showed high sensitivity and low variant detection variability for single-nucleotide variants, insertions and deletions, and fusions down to a variant allele frequency (VAF) of 0.5% in the reference samples and VAFs that were highly concordant with previous digital droplet PCR results in the patient samples. At reduced input amounts (20, 15, and 5 ng) and below VAFs of 0.5%, sensitivity was considerably lower and variant detection variability increased. Covering 523 tumor-associated genes, the assay demonstrated a convincing performance comparable to NGS-based ctDNA assays with smaller gene panels, highlighting its value to screen large numbers of different genes.
Subject(s)
Circulating Tumor DNA , Neoplasms , Humans , Circulating Tumor DNA/genetics , Mutation , Liquid Biopsy/methods , Neoplasms/diagnosis , Neoplasms/genetics , High-Throughput Nucleotide Sequencing/methods , Biomarkers, Tumor/geneticsABSTRACT
Bacterial biofilms on foreign surfaces are considered a primary cause of implant-related infections, which are challenging to treat. A new implant coating was developed, containing anti-infective silver within a biocompatible polymer carrier substance. In addition to its passive effect on the implant surface, highly concentrated anti-infective silver can be released as needed via the application of high-energy shock waves. This intervention could be applied transcutaneously in a clinical setting without the need for additional surgery. We investigated the inhibition of biofilm formation and the effectiveness of eradication after activation of the coating via shock waves in an in vitro biofilm model using Staphylococcus epidermidis RP62A. This was performed via scanning electron microscopy and quantitative microbiology. Additionally, we examined the cytotoxicity of the new coating on normal human fibroblasts and Saos-2 osteoblast-like cells, depending on the silver concentration. All studies were compared to uncoated titanium surfaces Ti6Al4V and a conventional electroplated silver coating. Cytotoxicity toward normal human fibroblasts and Saos-2 osteoblast-like cells increased with higher silver content but remained tolerable at 6%. Compared to uncoated Ti6Al4V and the electroplated silver coating, the new coating with a silver content of 4% and 6% exhibited a significant reduction in adherent bacteria by a factor of approximately 1000. This was also evident via microscopic examination of the surface morphology of the biofilms. Furthermore, following shock wave activation, no bacteria were detectable on either the implant or in the surrounding fluid after a 24 h period.
ABSTRACT
External factors can affect reproductive traits of breeding boars and especially the sensitive process of spermatogenesis. The aim of this study was to investigate probable influences of bedding materials (chipsy wood shavings (CWS), hemp straw (HS), linen straw (LS), spelt husks (SH), and regional wood shavings (RWS)) on semen traits of 40 randomly selected Piétrain boars (8 boars per group, age: 2.35 ± 1.23 years). After a six-week adaptation period, 40 fresh semen samples were collected weekly for four weeks and diluted in BTS (4 consecutive ejaculates per boar, 32 samples per group, 160 samples in total). Semen samples were analyzed using an extended range of spermatological methods (e.g., computer-assisted sperm analysis and flow cytometry). Generalized linear mixed models for each sperm parameter as well as the area under the curve for total sperm motility and thermo-resistance test were calculated. Materials LS and SH exceeded the standard maximum level for pesticide residues (VO (EG) No. 396/2005). Materials HS and LS presented the highest water-binding capacity of 413 % and 357 %, respectively, while SH showed the lowest value of 250 %. There were no significant (P > 0.05) differences between groups in any sperm characteristic, therefore indicating that bedding material had no influence on sperm quality. For most semen traits, however, we found significant (P ≤ 0.001) differences between sampling weeks. Based on pesticide results, we suggest CWS, RWS, or HS as possible bedding materials for pig production farms in the future. Furthermore, we strongly recommend a quality analysis of any new bedding material before use in swine husbandry.
Subject(s)
Semen , Sperm Motility , Animals , Male , Swine , Spermatozoa , Semen Analysis/veterinary , ReproductionABSTRACT
Implant-related infections are a significant concern in orthopedic surgery. A novel anti-infective implant coating made of bioresorbable polymer with silver nitrate was developed. A controlled release of silver ions into the vicinity of the prosthesis can be triggered on-demand by extracorporeal shock waves to effectively combat all clinically relevant microorganisms. Microscopy techniques were used to examine the effects of shock wave application on coated titanium discs. Cytotoxicity was measured using a fibroblast proliferation assay. The anti-infective effect was assessed by monitoring the growth curves of three bacterial strains and by conventional culture. Microscopic analysis confirmed surface disruption of the coatings, with a complete release of silver in the focus area after shock wave application. Spectrometry detected an increase in silver concentration in the surrounding of the discs that surpassed the minimum inhibitory concentration (MIC) for both S. epidermidis RP62A and E. coli ATCC 25922. The released silver demonstrated an anti-infective effect, significantly inhibiting bacterial growth, especially at 6% and 8% silver concentrations. Cytotoxicity testing showed decreasing fibroblast viability with increasing silver concentration in the coating, with 6% silver maintaining viability above 25%. Compared to a commonly used electroplated silver coating on the market, the new coating demonstrated superior antimicrobial efficacy and lower cytotoxicity.
ABSTRACT
BACKGROUND: Increasing antibiotic resistance has been reported as an issue in the systemic treatment of periprosthetic joint infection (PJI). Linezolid offers the advantages of high oral bioavailability and little resistance; however, efficacy in the treatment of PJI varies considerably, and studies reporting consistent surgical treatment are scarce. METHODS: This is a retrospective, single-center analysis of two-stage revisions performed between 2008 and 2017. We identified 111 patients who met the inclusion criteria. Oral linezolid was given for 28 days following 14 days of intravenous tailored antibiotics in resistant gram-positive PJI. A total of 64% of the patients had methicillin-resistant coagulase-negative staphylococci. The median follow-up was 43 (interquartile range (IQR) 30-57) months. RESULTS: 22% (24/111) of the patients underwent surgery for subsequent infection. The 5-year infection-free survival probability was 77% (95% confidence interval (CI) 69-85). A total of 5% of the patients (6/111) had the same organism at the time of reinfection. The patients with infections caused by other organisms than Coagulase-negative staphylococci tended to have a worse reinfection-free survivorship at five years (70% vs. 81%, p = 0.09). Furthermore, the patients with obesity tended to have reduced reinfection-free survivorship at five years (69% vs. 84%, p = 0.08). Overall, 5% (6/111) of the patients had blood count abnormalities with no treatment discontinuations. CONCLUSION: Two-stage revision arthroplasty with systemic oral linezolid treatment for resistant gram-positive PJI results in an infection control of 77% at the mid-term.