Krüppel-like factor 15 deficiency exacerbates osteoarthritis through reduced expression of peroxisome proliferator-activated receptor gamma signaling in mice.

OBJECTIVE: Krüppel-like zinc finger transcription factors (KLFs) play diverse roles in mammalian cell differentiation and development. In this study, we investigated the function of KLF15 in the progression of osteoarthritis (OA). METHODS: 0Destabilization of the medial meniscus (DMM) surgery was performed in 10-week-old male wild-type control (WT) mice and cartilage-specific KLF15 knockout (KO) mice. Histological analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining were performed. Morphological changes were measured using microcomputed tomography. Six mice from each group were analyzed (total number of mice analyzed: 60). In vitro, immunofluorescence, quantitative reverse transcription-polymerase chain reaction, and western blot analyses were performed. RESULTS: KLF15 KO DMM mice exhibited significant cartilage degradation compared to WT mice. According to the Osteoarthritis Research Society International cartilage OA-histopathology scoring system, the mean sum score in KLF15 KO mice was significantly higher than that in WT mice at 8 weeks after surgery. Immunohistochemistry results revealed KLF15 KO mice exhibited reduced peroxisome proliferator-activated receptor gamma (PPARγ) expression, increased pIKKα/ß, a disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) 5, and Matrix metalloproteinases (MMP13) expression, and reduced Forkhead box O (FOXO1) and Light chain 3B (LC3B) expression. Inhibition of PPARγ phosphorylation accelerated the effects of interleukin (IL) 1ß-treatment in both KLF15 KO and WT chondrocytes, and activation of PPARγ expression canceled the IL1ß-induced catabolic effects. CONCLUSION: Our results indicated that the OA phenotype of KLF15 KO DMM mice was influenced by reduced PPARγ expression, including enhanced pIKKα/ß, ADAMTS5, and MMP13 expression, reduced autophagy, and increased apoptosis. KLF15 regulation may constitute a possible therapeutic strategy for the treating OA.

Hypermucoviscous Carbapenem-Resistant Klebsiella pneumoniae ST25 Infect Human Intestinal Epithelial Cells and Induce Moderate Inflammation.

Klebsiella pneumoniae is an opportunistic pathogen that can produce moderate and severe infections in immunosuppressed hosts. In recent years, an increase in the isolation of hypermucoviscous carbapenem-resistant K. pneumoniae with sequence type 25 (ST25) in hospitals in Norwest Argentina was observed. This work aimed to study the virulence and inflammatory potential of two K. pneumoniae ST25 strains (LABACER01 and LABACER27) in the intestinal mucosa. The human intestinal Caco-2 cells were infected with the K. pneumoniae ST25 strains, and their adhesion and invasion rates and changes in the expression of tight junction and inflammatory factors genes were evaluated. ST25 strains were able to adhere and invade Caco-2 cells, reducing their viability. Furthermore, both strains reduced the expression of tight junction proteins (occludin, ZO-1, and claudin-5), altered permeability, and increased the expression of TGF-ß and TLL1 and the inflammatory factors (COX-2, iNOS, MCP-1, IL-6, IL-8, and TNF-α) in Caco-2 cells. The inflammatory response induced by LABACER01 and LABACER27 was significantly lower than the one produced by LPS or other intestinal pathogens, including K. pneumoniae NTUH-K2044. No differences in virulence and inflammatory potential were found between LABACER01 and LABACER27. In line with these findings, no major differences between the strains were found when the comparative genomic analysis of virulence factors associated with intestinal infection/colonization was performed. This work is the first to demonstrate that hypermucoviscous carbapenem-resistant K. pneumoniae ST25 infects human intestinal epithelial cells and induces moderate inflammation.

Immunobiotic Ligilactobacillus salivarius FFIG58 Confers Long-Term Protection against Streptococcus pneumoniae.

Previously, we isolated potentially probiotic Ligilactobacillus salivarius strains from the intestines of wakame-fed pigs. The strains were characterized based on their ability to modulate the innate immune responses triggered by the activation of Toll-like receptor (TLR)-3 or TLR4 signaling pathways in intestinal mucosa. In this work, we aimed to evaluate whether nasally administered L. salivarius strains are capable of modulating the innate immune response in the respiratory tract and conferring long-term protection against the respiratory pathogen Streptococcus pneumoniae. Infant mice (3-weeks-old) were nasally primed with L. salivarius strains and then stimulated with the TLR3 agonist poly(I:C). Five or thirty days after the last poly(I:C) administration mice were infected with pneumococci. Among the strains evaluated, L. salivarius FFIG58 had a remarkable ability to enhance the protection against the secondary pneumococcal infection by modulating the respiratory immune response. L. salivarius FFIG58 improved the ability of alveolar macrophages to produce interleukin (IL)-6, interferon (IFN)-γ, IFN-ß, tumor necrosis factor (TNF)-α, IL-27, chemokine C-C motif ligand 2 (CCL2), chemokine C-X-C motif ligand 2 (CXCL2), and CXCL10 in response to pneumococcal challenge. Furthermore, results showed that the nasal priming of infant mice with the FFIG58 strain protected the animals against secondary infection until 30 days after stimulation with poly(I:C), raising the possibility of using nasally administered immunobiotics to stimulate trained immunity in the respiratory tract.

Bearing Separation From the Lateral Wall of the Tibial Component Is a Risk of Anterior Dislocation of the Mobile Bearing in Oxford Unicompartmental Knee Arthroplasty.

BACKGROUND: Bearing dislocation is a serious complication after Oxford unicompartmental knee arthroplasty. Bearing separation from the lateral wall can cause it to spin (90° horizontal rotation) and eventually dislocate because there is just a 2 mm difference in height in both the lateral and medial sides from the bottom of the bearing, compared with the anterior (5 mm) and posterior (3 mm) sides. The details of this problem have not been previously examined. METHODS: Twenty-one dislocations in 12 patients were retrospectively analyzed. Bearing separation was defined as the bearing position being sufficiently distant from the lateral wall of the tibial component to allow spinning. We analyzed the incidence of separation, the direction and the recurrence of the dislocations, and their causes and treatments. RESULTS: Five of the 12 patients had separation. Of the total of 21 dislocations, 11 occurred in cases of separation (52%). Seven of 11 anterior dislocations were found to have separation, whereas nine of 13 posterior dislocations occurred without separation (P = .0237). Three of 5 patients with separation had recurrence of dislocation, and eventually 2 underwent revision to fixed-bearing unicompartmental knee arthroplasty. CONCLUSION: Bearing separation from the lateral wall of the tibial component can cause bearing dislocation, especially in an anterior direction. To prevent separation, the wall-bearing distance should be evaluated before the keel slot preparation, with manipulation as necessary. Conversely, posterior dislocation was predominant in our nonseparation cases.

Genetic variation in Japanese Holstein cattle for EBL development.

BACKGROUND: Infection with bovine leukemia virus (BLV), the causative agent for enzootic bovine leukosis (EBL), is increasing in dairy farms of Japan. The tendency of tumor development following BLV infection in certain cow families and bull lines has previously been described. We therefore hypothesized the existence of a genetic component which differentiates cattle susceptibility to the disease. RESULTS: We analyzed routinely collected large-scale data including postmortem inspection data, which were combined with pedigree information and epidemiological data of BLV infection. A total of 6,022 postmortem inspection records of Holstein cattle, raised on 226 farms served by a regional abattoir over 10 years from 2004 to 2015, were analyzed for associations between sire information and EBL development. We then identified statistically the relative susceptibility to EBL development for the progeny of specific sires and paternal grandsires (PGSs). The heritability of EBL development was calculated as 0.19. Similarly, proviral loads (PVLs) of progeny from identified sires and PGSs were analyzed, but no significant differences were found. CONCLUSIONS: These observations suggest that because EBL development in our Holstein population is, at least in part, influenced by genetic factors independent of PVL levels, genetic improvement for lower incidence of EBL development in cattle notwithstanding BLV infection is possible.

Improved implant alignment accuracy with an accelerometer-based portable navigation system in medial unicompartmental knee arthroplasty.

PURPOSE: This study aimed to examine the accuracy of tibial implant alignment using an accelerometer-based portable navigation system in unicompartmental knee arthroplasty (UKA). METHODS: This retrospective matched case-control study reviewed 51 UKAs performed using an accelerometer-based portable navigation system, matched with 51 UKAs performed using conventional extramedullary rods. Coronal alignment and posterior slope of the tibial implant were measured on postoperative radiographs, and differences from preoperative planning were examined. Outliers and accuracy of tibial implant alignment were compared between the portable navigation and conventional groups using Fisher's exact test and Mann-Whitney U test, respectively. RESULTS: In the portable navigation group, 100% of the implants were aligned within 3.0° of both target coronal and sagittal implant alignment. In the conventional group, 76.5% and 88.2% of the implants were within 3.0° of both target coronal and sagittal implant alignment. Statistical analysis revealed that outliers of coronal and sagittal alignment were significantly less in the portable navigation group than in the conventional group (P < 0.05). In addition, the absolute value difference between postoperative measurement and preoperative planning of both coronal and sagittal alignment was significantly smaller in the portable navigation group than in the conventional group (P < 0.05). CONCLUSION: The portable navigation system improved the accuracy of tibial implant alignment in UKA. We found that 100% of the implants were aligned within 3.0° of both target coronal and sagittal implant alignment. The portable navigation system decreased the outliers of tibial coronal and sagittal alignment. LEVEL OF EVIDENCE: Retrospective case-control study, Level III.

Emerging Role of Extracellular Vesicles in Embryo-Maternal Communication throughout Implantation Processes.

In ruminants, the establishment of proper conceptus-endometrial communication is essential for conceptus implantation and subsequent successful placentation. Accumulated evidence supports the idea that extracellular vesicles (EVs) present in uterine lumen are involved in conceptus-endometrial interactions during the preimplantation period. EVs make up a new field of intercellular communicators, which transport a variety of bioactive molecules, including soluble and membrane-bound proteins, lipids, DNA, and RNAs. EVs thus regulate gene expression and elicit biological effects including increased cell proliferation, migration, and adhesion in recipient cells. Uterine EVs are interactive and coordinate with ovarian progesterone (P4), trophectoderm-derived interferon tau (IFNT) and/or prostaglandins (PGs) in the physiological or pathological microenvironment. In this review, we will focus on intrauterine EVs in embryo-maternal interactions during the early stage of pregnancy, especially the implantation period in ruminant ungulates.

Immunoregulatory effects triggered by immunobiotic Lactobacillus jensenii TL2937 strain involve efficient phagocytosis in porcine antigen presenting cells.

BACKGROUND: Immunobiotic Lactobacillus jensenii TL2937 modulates porcine mononuclear phagocytes from Peyer's patches (PPMPs) and induces a differential production of pro- and anti-inflammatory cytokines in response to Toll-like receptor (TLR)-4 activation. In view of the important role played by phagocytosis in the activation of antigen presenting cells (APCs), the aim of the present work was to examine the interaction of TL2937 with porcine PPMPs focusing on phagocytosis. In addition, this study aimed to investigate whether the effects of L. jensenii TL2937 in porcine blood monocyte-derived dendritic cells (MoDCs) are similar to those found in PPMPs considering that MoDCs do not recapitulate all functions of mucosal APCs. RESULTS: Studies showed a high ability of porcine CD172a(+) PPMPs to phagocytose L. jensenii TL2937. Interestingly, our results also revealed a reduced capacity of the non-immunomodulatory L. plantarum TL2766 to be phagocytosed by those immune cells. Phagocytosis of L. jensenii TL2937 by porcine PPMPs was partially dependent on TLR2. In addition, we demonstrated that TL2937 strain was able to improve the expression of IL-1ß, IL-12 and IL-10 in immature MoDCs resembling the effect of this immunobiotic bacterium on PPMPs. Moreover, similarly to PPMPs those immunomodulatory effects were related to the higher capacity of TL2937 to be phagocytosed by immature MoDCs. CONCLUSIONS: Microbial recognition in APCs could be effectively mediated through ligand-receptor interactions that then mediate phagocytosis and signaling. For the immunobiotic strain TL2937, TLR2 has a partial role for its interaction with porcine APCs and it is necessary to investigate the role of other receptors. A challenge for future research will be advance in the full understanding of the molecular interactions of immunobiotic L. jensenii TL2937 with porcine APCs that will be crucial for the successful development of functional feeds for the porcine host. This study is a step in that direction.

Oral delivery of Lactococcus lactis that secretes bioactive heme oxygenase-1 alleviates development of acute colitis in mice.

BACKGROUND: Mucosal delivery of therapeutic proteins using genetically modified strains of lactic acid bacteria (gmLAB) is being investigated as a new therapeutic strategy. METHODS: We developed a strain of gmLAB, Lactococcus lactis NZ9000 (NZ-HO), which secretes the anti-inflammatory molecule recombinant mouse heme oxygenase-1 (rmHO-1). The effects of short-term continuous oral dosing with NZ-HO were evaluated in mice with dextran sulfate sodium (DSS)-induced acute colitis as a model of inflammatory bowel diseases (IBD). RESULTS: We identified the secretion of rmHO-1 by NZ-HO. rmHO-1 was biologically active as determined with spectroscopy. Viable NZ-HO was directly delivered to the colon via oral administration, and rmHO-1 was secreted onto the colonic mucosa in mice. Acute colitis in mice was induced by free drinking of 3 % DSS in water and was accompanied by an increase in the disease activity index score and histopathological changes. Daily oral administration of NZ-HO significantly improved these colitis-associated symptoms. In addition, NZ-HO significantly increased production of the anti-inflammatory cytokine interleukin (IL)-10 and decreased the expression of pro-inflammatory cytokines such as IL-1α and IL-6 in the colon compared to a vector control strain. CONCLUSIONS: Oral administration of NZ-HO alleviates DSS-induced acute colitis in mice. Our results suggest that NZ-HO may be a useful mucosal therapeutic agent for treating IBD.

Immunobiotic Lactobacillus jensenii as immune-health promoting factor to improve growth performance and productivity in post-weaning pigs.

BACKGROUND: Immunoregulatory probiotics (immunobiotics) have been proposed to improve piglets' immune system to avoid intestinal infections and reduce unproductive inflammation after weaning. Previously, it was demonstrated that Lactobacillus jensenii TL2937 (LjTL2937) attenuated the inflammatory response triggered by activation of Toll-like receptor 4 (TLR-4) in porcine intestinal epithelial (PIE) cells and antigen presenting cells (APCs) from porcine Peyer's patches (PP). OBJECTIVE: In view of the critical importance of PIE-APCs interactions in the regulation of intestinal immune responses, we aimed to examine the effect of LjTL2937 on activation patterns of APCs from swine PPs in co-cultures with PIE cells. In addition, we investigated whether LjTL2937 was able to beneficially modulate intestinal immunity of piglets after weaning to improve immune-health status. RESULTS: Stimulation of PIE-APCs co-cultures with LjTL2937 increased the expression of MHC-II, CD80/86, IL-10, and Bcl-3 in CD172a+CD11R1- and CD172a+CD11R1high APCs. In addition, the TL2937 strain caused the upregulation of three negative regulators of TLR4 in PIE cells: MKP-1, Bcl-3 and A20. These changes significantly reduced the inflammatory response triggered by TLR4 activation in PIE-APCs co-cultures. The in vivo experiments using castrated male piglets (crossbreeding (LWD) with Landrace (L), Large Yorkshire (W) and Duroc (D))of 3 weeks of age demonstrated that feeding with LjTL2937 significantly reduced blood complement activity and C reactive protein concentrations while no changes were observed in blood leukocytes, ratio of granulocytes to lymphocyte numbers, macrophages' activity and antibody levels. In addition, treatment with LjTL2937 significantly improved growth performance and productivity, and increased carcass quality. CONCLUSIONS: We demonstrated that the use of immunobiotics strains like LjTL2937, as supplemental additives for piglets feedings, could be used as a strategy to maintain and improve intestinal homeostasis; that is important for the development of the pig and for health and performance throughout the productive life of the animal.

Varus placement of the tibial component reduces the potential risk of fracture with adequate bony coverage in the Oxford unicompartmental knee arthroplasty.

A short keel-cortex distance (KCD), especially to the posterior cortex, is a potential risk factor for tibial plateau fracture after Oxford mobile-bearing unicompartmental knee arthroplasty (OUKA). This study aimed to evaluate the effect of tibial component alignment in the coronal plane and tibial proximal morphology on the KCD. Included in this study were 51 patients scheduled for primary Oxford medial unicompartmental knee arthroplasty (UKA). The anterior and posterior KCD were preoperatively assessed using 3D simulation software with the component set perpendicular to the tibial mechanical axis (neutral), 3° valgus, 3° varus, and 6° varus, relative to neutral alignment. We evaluated the existence of overhanging medial tibial condyle where the medial eminence line, the line including the medial tibial eminence parallel to the tibial axis, passes outside of the tibial shaft. In all component alignments, patients with a medial overhanging condyle had significantly shorter posterior KCD than those without. In patients with a medial overhanging condyle, the posterior KCD significantly increased when the tibial component was placed in 3° varus (4.6 ± 1.5 mm, P = 0.003 vs neutral, P < 0.001 vs 3° valgus) and 6° varus (5.0 ± 1.4 mm, P < 0.001 vs neutral, P < 0.001 vs 3° valgus) compared with in neutral (3.5 ± 1.9 mm) or 3° valgus (2.8 ± 1.8 mm). In OUKA, varus implantation increased the KCD. This could potentially decrease the risk of fracture, even in knees with the overhanging medial condyle. Conversely, valgus implantation of the tibial component shortened the KCD, and should therefore be avoided.

In vitro evaluation of the immunomodulatory and wakame assimilation properties of Lactiplantibacillus plantarum strains from swine milk.

The emergence and spread of antibiotic resistance threat forced to explore alternative strategies for improving the resistance to pathogens in livestock production. Probiotic lactic acid bacteria represent an alternative for this objective. In this study, seven Lactiplantibacillus plantarum strains from porcine colostrum and milk were isolated, identified and characterized in terms of their abilities to modulate immunity in porcine intestinal epithelial (PIE) cells. Then, two potential immunoregulatory strains were studied in terms of their ability to utilize and grow in wakame (Undaria pinnafida). Isolates were identified by 16S rRNA gene and evaluated by studying their interaction with PIE cells. The expressions of peptidoglycan recognition proteins (PGRPs), nucleotide-binding oligomerization domain (NODs), host defense peptides (pBD), and type I interferons (IFNs) were evaluated by RT-qPCR. The strain 4M4417 showed a remarkable capacity to differentially regulate the expression of PGRP1, PGRP3, NOD1, NOD2, and pBD1 in PIE cells. On the other hand, the strain 4M4326 was the most efficient to improve the expression of IFN-α and IFN-ß in PIE cells challenged with poly (I:C). Both L. plantarum 4M4326 and 4M4417 were characterized in terms of their ability to utilize wakame. Results demonstrated that both strains efficiently grew in wakame-based broth. Our results suggest that L. planatrum 4M4326 and 4M4417 are interesting candidates to develop immunomodulatory feeds based on wakame utilization. These new immunosynbiotic feeds could help to reduce severity of intestinal infections and improve immune health status in pigs.

Establishment of porcine fecal-derived ex vivo microbial communities to evaluate the impact of livestock feed on gut microbiome.

Sustainable livestock production requires reducing competition for food and feed resources and increasing the utilization of food by-products in livestock feed. This study describes the establishment of an anaerobic batch culture model to simulate pig microbiota and evaluate the effects of a food by-product, wakame seaweed stalks, on ex vivo microbial communities. We selected one of the nine media to support the growth of a bacterial community most similar in composition and diversity to that observed in pig donor feces. Supplementation with wakame altered the microbial profile and short-chain fatty acid composition in the ex vivo model, and a similar trajectory was observed in the in vivo pig experimental validation. Notably, the presence of wakame increased the abundance of Lactobacillus species, which may have been due to cross-feeding with Bacteroides. These results suggest the potential of wakame as a livestock feed capable of modulating the pig microbiome. Collectively, this study highlights the ability to estimate the microbiome changes that occur when pigs are fed a specific feed using an ex vivo culture model.

Bacterium-like Particles from Corynebacterium pseudodiphtheriticum as Mucosal Adjuvant for the Development of Pneumococcal Vaccines.

Previously, it was shown that intranasally (i.n.) administered Corynebacterium pseudodiphtheriticum 090104 (Cp) or CP-derived bacterium-like particles (BLPs) improve the immunogenicity of the pneumococcal conjugate vaccine (PCV). This work aimed to deepen the characterization of the adjuvant properties of Cp and CP-derived BLPs for their use in the development of pneumococcal vaccines. The ability of Cp and CP-derived BLPs to improve both the humoral and cellular specific immune responses induced by i.n. administered polysaccharide-based commercial pneumococcal vaccine (Pneumovax 23®) and the chimeric recombinant PSPF (PsaA-Spr1875-PspA-FliC) protein was evaluated, as well as the protection against Streptococcus pneumoniae infection in infant mice. Additionally, whether the immunization protocols, including Cp and CP-derived BLPs, together with the pneumococcal vaccines can enhance the resistance to secondary pneumococcal pneumonia induced after inflammatory lung damage mediated by the activation of Toll-like receptor 3 (TLR3) was assessed. The results showed that both Cp and CP-derived BLPs increased the immunogenicity and protection induced by two pneumococcal vaccines administered through the nasal route. Of note, the nasal priming with the PSPF T-dependent antigen co-administered with Cp or CP-derived BLPs efficiently stimulated humoral and cellular immunity and increased the resistance to primary and secondary pneumococcal infections. The CP-derived BLPs presented a stronger effect than live bacteria. Given safety concerns associated with live bacterium administration, especially in high-risk populations, such as infants, the elderly, and immunocompromised patients, BLPs emerge as an attractive mucosal adjuvant to improve the host response to pneumococcal infections and to enhance the vaccines already in the market or in development.

Advanced application of bovine intestinal epithelial cell line for evaluating regulatory effect of lactobacilli against heat-killed enterotoxigenic Escherichia coli-mediated inflammation.

BACKGROUND: Previously, a bovine intestinal epithelial cell line (BIE cells) was successfully established. This work hypothesized that BIE cells are useful in vitro model system for the study of interactions of microbial- or pathogen-associated molecular patterns (MAMPs or PAMPs) with bovine intestinal epithelial cells and for the selection of immunoregulatory lactic acid bacteria (LAB). RESULTS: All toll-like receptor (TLR) genes were expressed in BIE cells, being TLR4 one of the most strongly expressed. We demonstrated that heat-stable PAMPs of enterotoxigenic Escherichia coli (ETEC) significantly enhanced the production of IL-6, IL-8, IL-1α and MCP-1 in BIE cells by activating both NF-κB and MAPK pathways. We evaluated the capacity of several lactobacilli strains to modulate heat-stable ETEC PAMPs-mediated inflammatory response in BIE cells. Among these strains evaluated, Lactobacillus casei OLL2768 attenuated heat-stable ETEC PAMPs-induced pro-inflammatory response by inhibiting NF-κB and p38 signaling pathways in BIE cells. Moreover, L. casei OLL2768 negatively regulated TLR4 signaling in BIE cells by up-regulating Toll interacting protein (Tollip) and B-cell lymphoma 3-encoded protein (Bcl-3). CONCLUSIONS: BIE cells are suitable for the selection of immunoregulatory LAB and for studying the mechanisms involved in the protective activity of immunobiotics against pathogen-induced inflammatory damage. In addition, we showed that L. casei OLL2768 functionally modulate the bovine intestinal epithelium by attenuating heat-stable ETEC PAMPs-induced inflammation. Therefore L. casei OLL2768 is a good candidate for in vivo studying the protective effect of LAB against intestinal inflammatory damage induced by ETEC infection or heat-stable ETEC PAMPs challenge in the bovine host.

Bearings can dislocate with smaller femoral components and thicker bearings in Oxford™ medial unicompartmental knee arthroplasty.

BACKGROUND: A mobile bearing can dislocate when joint laxity is larger than jumping height, the height difference between the bottom and the peak of the bearing (the highest point of the upper bearing surface on each side). Significant laxity due to improper gap balancing should therefore be avoided. However, once the bearing rotates vertically on the tibial component, the bearing can dislocate with smaller laxity than the jumping height. We mathematically calculated the required laxity for dislocation (RLD) and the required rotation of the bearing for dislocation (RRD). The current study addressed the question: 1) could the femoral component size and the bearing thickness affect the RLD and RRD? HYPOTHESIS: The femoral component size and the bearing thickness could affect the MLD and MRD. METHODS: The RLD and RRD were calculated using the bearing dimensions provided by the manufacturer with femoral component size, bearing thickness, and directions (anterior, posterior, and medial/lateral) as the variables on a two-dimensional basis. RESULTS: The RLD was 3.4 to 5.5mm in the anterior, 2.3 to 3.8mm in the posterior, and 1.4 to 2.4mm in the medial or lateral directions. The RLD decreased with a smaller femoral size or a thicker bearing. Similarly, the RRD decreased with a smaller femoral size or a thicker bearing thickness in all directions. CONCLUSIONS: Increased bearing thickness and decreased femoral component size deceased the RLD and RRD, which would relate to an increased risk of dislocation. Selecting the femoral component as large as possible and the bearing as thin as possible would therefore be helpful in the prevention of dislocation. LEVEL OF EVIDENCE: III; comparative computer simulation study.

Mobile bearing orbit on the tibial component in Oxford unicompartmental knee arthroplasty.

PURPOSE: To evaluate the bearing orbit of the tibial component during extension-flexion motion in Oxford unicompartmental knee arthroplasty. MATERIALS AND METHODS: A total of 32 knees in 25 patients with medial osteoarthritis who underwent Oxford unicompartmental knee arthroplasty were evaluated. The distance between the vertical wall of the tibial component and the bearing (wall-bearing distance) and that between the anterior edge of the tibial component and the bearing (sagittal bearing position) were measured at 0°, 30°, 60°, 90° and 120° knee flexion with neutral tibial rotation (extension-flexion motion), and internal and external tibial rotation with 90° knee flexion (tibial rotation motion). A custom-made rounded trial bearing and caliper were used for this measurement. We calculated the wall-bearing distance, change in extension-flexion motion and tibial rotation motion. Wall-bearing distances and change in wall-bearing distance were compared using ANOVA or t-test. RESULTS: The wall-bearing distance was smallest at 60° and increased 1.0 ± 1.1 mm in knee extension and 1.1 ± 1.5 mm in knee flexion. The bearing moved posteriorly with knee flexion, and the sagittal bearing position increased by 8.1 ± 3.4 mm during extension-flexion motion. Consequently, the bearing moved in a rough C-shaped orbit of the tibial component. CONCLUSIONS: The mobile bearing moves in a rough C-shape and is mostly close to the vertical wall of the tibial component at 60°. The wall-bearing distance can change during extension-flexion motion and might be influenced by tibial component rotation. To avoid bearing separation from or contact with the vertical wall that may cause bearing dislocation, the wall-bearing distance should be evaluated before keel slot preparation.

Intraoperative avulsion fracture of the intercondylar eminence in Oxford mobile-bearing unicompartmental knee arthroplasty: Case report.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) can provide good postoperative results and long term survival, but there may be complications. We present a rare case of avulsion fracture of the intercondylar eminence during UKA surgery. CASE PRESENTATION: An 88-year-old man had right-knee pain with anteromedial osteoarthritis. Oxford partial knee UKA (Zimmer Biomet, Warsaw, IN) was performed by the senior author by the under-vastus approach using Microplasty instruments. During the final check of the range of motion, an avulsion fracture of the intercondylar eminence occurred at the terminal extension. A 4.0 mm cannulated cancellous screw was inserted into the intercondylar eminence from just in front of the anterior cruciate ligament to the posterior tibial cortex. Six months postoperatively, bony fusion was confirmed by lateral radiography. Two years after the surgery, the patient was fully satisfied. The flexion angle was 125°, but still with an extension limit of 10°. DISCUSSION: Avulsion fracture of the intercondylar eminence can be caused by hyperextension and/or the ACL becoming tighter in full extension of the knee. In this patient, avulsion fracture also probably occurred due to increased tension of the ACL in the fully extended position. After making the horizontal cut, we inserted a thin metal plate to prevent deeper vertical cuts, but an excessive horizontal cut was a possible cause of the fracture. As treatment for avulsion fracture of the intercondylar eminence, fixation of the cannulated cancellous screw resulted in uneventful bone fusion. We recommend having a cannulated cancellous screw at hand for such complications and for other potential intraoperative problems, such as tibial plateau fracture. Further investigation into limited postoperative extension might be needed. CONCLUSION: Our patient had intraoperative avulsion fracture of the intercondylar eminence, a relatively rare complication of Oxford UKA which is probably caused by the extension being tight and/or an excessive horizontal cut. Having a cannulated cancellous screw at hand is advised, and attention should be paid to postoperative limit of extension.

Incomplete Screw Thread Engagement of Proximal Fragment: A Possible Failure Risk After Internal Fixation for Femoral Neck Fractures.

Background For successful internal fixation for femoral neck fracture, the sliding mechanism of the screw is important because it can induce inter-fragmental compression. The thread should penetrate the fracture line and be located within the proximal fragment. If screw thread engagement is incomplete and a part of the thread remains within the distal fragment, the screw sliding can be disturbed, potentially leading to fixation failure. We hypothesized that screw thread in the fracture is a risk of fixation failure. Methods We studied 133 hips that underwent internal fixation for femoral neck fracture using dual sliding and compression screws (DSCS) with 20 mm threads. The existence of incomplete thread engagement and fixation failure (cut out, perforation, pseudoarthrosis, or femoral neck shortening) were evaluated on anteroposterior hip radiography postoperatively. The distances from the thread end to the fracture line, screw head to the femoral head cortex, and femoral head diameter were measured to analyze their relationships with any incomplete thread engagement and fixation failure. Differences in evaluation data were assessed using Fisher's exact test, Student's t-test, and receiver operating characteristic (ROC) analysis. Results Forty-six cases had at least one screw with incomplete thread engagement, and the other 87 hips had a complete engagement. The failure rate in the group of hips with incomplete thread engagement was significantly higher (7/46, 15.2%) than that in the group of hips with complete thread engagement (3/87, 3.4%) (P = 0.032). Incomplete thread engagement was found in 59 out of 266 screws (22.2%), and a femoral head ≤ 43.9 mm in diameter was associated with an increased risk of incomplete thread engagement. Most incomplete thread engagement screws (81.4%) had < 5 mm thread length within the distal fragment. Conclusion A partially threaded screw is a significant risk of fixation failure after internal fixation for a femoral neck fracture. The smaller femoral head diameter increases the possibility of incomplete thread engagement. Shortening the thread length by 5 mm may help to avoid incomplete thread engagement.

Oral Administration of Lacticaseibacillus rhamnosus CRL1505 Modulates Lung Innate Immune Response against Klebsiella pneumoniae ST25.

Orally administered Lacticaseibacillus rhamnosus CRL1505 enhances respiratory immunity, providing protection against respiratory viruses and Streptococcus pneumoniae. However, the capacity of the CRL1505 strain to improve respiratory immunity against Gram-negative bacterial infections has not been evaluated before. The aim of this work was to evaluate whether the Lcb. rhamnosus CRL1505 was able to beneficially regulate the respiratory innate immune response and enhance the resistance to hypermucoviscous KPC-2-producing Klebsiella pneumoniae of the sequence type 25 (ST25). BALB/c mice were treated with the CRL1505 strain via the oral route and then nasally challenged with K. pneumoniae ST25 strains LABACER 01 or LABACER 27. Bacterial cell counts, lung injuries and the respiratory and systemic innate immune responses were evaluated after the bacterial infection. The results showed that K. pneumoniae ST25 strains increased the levels of TNF-α, IL-1ß, IL-6, IFN-γ, IL-17, KC and MPC-1 in the respiratory tract and blood, as well as the numbers of BAL neutrophils and macrophages. Mice treated with Lcb. rhamnosus CRL1505 had significantly lower K. pneumoniae counts in their lungs, as well as reduced levels of inflammatory cells, cytokines and chemokines in the respiratory tract and blood when compared to infected controls. Furthermore, higher levels of the regulatory cytokines IL-10 and IL-27 were found in the respiratory tract and blood of CRL1505-treated mice than controls. These results suggest that the ability of Lcb. rhamnosus CRL1505 to help with the control of detrimental inflammation in lungs during K. pneumoniae infection would be a key feature to improve the resistance to this pathogen. Although further mechanistic studies are necessary, Lcb. rhamnosus CRL1505 can be proposed as a candidate to improve patients' protection against hypermucoviscous KPC-2-producing strains belonging to the ST25, which is endemic in the hospitals of our region.