More than 3 mm of preoperative medial meniscal extrusion is identified as a key risk factor for varus progression in limb alignment after arthroscopic repair of medial meniscus posterior root tear.

PURPOSE: To investigate the risk factors for varus progression after arthroscopic medial meniscal posterior root tear (MMPRT) repair and to compare the clinical outcomes between two groups: one with more varus progression and the other with less varus progression. METHODS: Patients who underwent isolated arthroscopic repair of MMPRT between 2015 and 2020 were enroled, and 2-year follow-up data were collected. Participants were categorized into two groups based on preoperative values of the weight-bearing line (WBL) ratio: group A with <5.9% increase and group B with ≥5.9% increase. Various factors, including demographic features and radiological findings, were analysed and compared between the two groups. Intra-meniscal signal intensity, meniscal healing, medial meniscal extrusion (MME), and articular cartilage grade were assessed preoperatively and 1-year postoperatively using coronal magnetic resonance imaging. RESULTS: The final cohort consisted of 34 patients in group A and 46 in group B, with a mean age of 55.8 ± 11.2 and 59.8 ± 6.6 years, respectively. Preoperative WBL ratio and cartilage lesions in the medial compartment did not differ between the groups. Preoperative MME were significantly lower in group A than those in group B (2.6 ± 0.6 mm in group A and 3.5 ± 0.7 mm in group B, p < 0.05). Patient-reported outcomes at the 2-year follow-up did not differ between the two groups (n. s.). In a logistic analysis, the odds ratio of MME was 2.1 (p < 0.05), and the cutoff value of MME was 3.02 mm. CONCLUSION: Preoperative MME is a risk factor for varus progression. However, no differences in patient-reported outcomes were observed at 2-year follow-up, even in the group with greater varus progression. LEVEL OF EVIDENCE: Level IV.

Anatomic femoral tunnel position in medial patellofemoral ligament reconstruction: anterior versus posterior.

BACKGROUND: This study aimed to compare the clinical and radiological outcomes of medial patellofemoral ligament reconstruction (MPFLR) between anatomic femoral tunnel positions at anterior and posterior footprints. METHODS: Fifty-seven patients who underwent MPFLR for patellofemoral instability with anterior or posterior femoral tunnels between 2014 and 2021 with at least 2 years of follow-up were retrospectively analyzed. Based on postoperative images, the femoral tunnel positions anterior to the line connecting the adductor tubercle and medial epicondyle were assigned to the anterior group, group A, and those posterior to the line to the posterior group, group P. Thirty-two patients were included in group A (mean age, 22.4 ± 8.8 years), and another 25 patients were included in group P (mean age, 21.1 ± 6.1 years). The International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Tegner activity score, Kujala score, and complications were evaluated. Radiologically, the Caton-Deschamps index (CDI), patellar tilt angle, and patellofemoral osteoarthritis (PFOA) using the Kellgren-Lawrence (KL) scale were evaluated. The patellofemoral cartilage status according to the International Cartilage Repair Society (ICRS) grade, bone contusion, femoral tunnel enlargement, and MPFL graft signal intensity were also evaluated. RESULTS: All clinical scores significantly improved in both groups (p < 0.01). No differences were noted between the two groups in terms of their preoperative demographic data, postoperative clinical scores (IKDC, Lysholm, Tegner, and Kujala), complications, or radiological findings (CDI, patellar tilt angle, PFOA, bone contusion, femoral tunnel enlargement, and graft signal intensity). The ICRS grade for the medial facet of the patella progressed in group A (30%, p = 0.02) but not in group P (18%, p = n.s.). Additionally, no significant differences were observed in the other compartments of the patellofemoral joint. CONCLUSIONS: The clinical outcomes were significantly improved in both groups; however, MPFLR with anterior femoral tunnel position had worse cartilage status on the medial facet of the patella than the posterior femoral tunnel position. LEVEL OF EVIDENCE: Level III.

Aseptic survival of the 1.5-stage exchange arthroplasty for periprosthetic joint infection was acceptable when using an autoclaved femoral component and a new polyethylene insert.

PURPOSE: To investigate the aseptic survival of 1.5-stage exchange arthroplasty for periprosthetic joint infection (PJI) after total knee arthroplasty (TKA). METHODS: Eighty-eight cases of 1.5-stage exchange arthroplasty for PJI without reinfection were retrospectively analysed. The autoclaved femoral component and new polyethylene insert (PE) were implanted using antibiotic mixed cement. The explanted tibial component was not reinserted. The Western Ontario and McMaster Universities Osteoarthritis Index and range of motion were clinically evaluated preoperatively and at the last follow-up (the last time for the implant in situ). Radiographically, hip-knee-ankle angle (HKA) and component positions were measured preoperatively, postoperatively (1 month after the 1.5-stage exchange arthroplasty), and at the last follow-up. The survival rate was analysed using the Kaplan-Meier method, in which failure was defined as reoperation due to aseptic failure. Mean period to failure and failure site were analysed. Factors affecting survival were investigated in terms of demographics and inappropriateness of the postoperative HKA (HKA > 0 ± 3°) and component positions (α angle > 95 ± 3°, ß angle > 90 ± 3°, γ angle > 3 ± 3°, and δ angle > 87 ± 3°). RESULTS: The spacer in-situ time was 3.7 years (0.2-6.4). The clinical results improved hip-knee-ankle significantly at the last follow-up. Radiographically, the average HKA was valgus 0.1° postoperatively. The average α, ß, γ, and δ angles of the postoperative component positions were 95.9°, 90.4°, 3.8°, and 86.7°, respectively. The 1-, 2-, and 5-year postoperative survival rates were 90.9%, 86.4%, and 80.6%, respectively. The mean period to failure was 2.0 years (0.2-5.3). There were 18 cases of aseptic loosening (20.8%), occurring on both the femur and tibial sides in 1 knee, and only on the tibial side in 17 knees. Inappropriate coronal position of the PE (ß angle > 90 ± 3°) was a significant factor affecting survival (odds ratio = 5.491; p = 0.011). CONCLUSION: The aseptic survival of the 1.5-stage exchange arthroplasty was acceptable when using an autoclaved femoral component and new PE. The appropriate coronal position of the PE helps ensure favourable survival of 1.5-stage exchange arthroplasty. LEVEL OF EVIDENCE: IV.

Additional anteromedial staple fixation prevents changes in the posterior tibial slope in retrotuberosity bi-planar open-wedge high tibial osteotomy.

PURPOSE: To compare the changes in posterior tibial slope (PTS) between retrotuberosity biplane open-wedge high tibial osteotomies (RT-OWHTOs) with and without additional anteromedial staple fixation. METHODS: Seventy-nine and 77 cases of RT-OWHTOs without (Group N) and with (Group S) additional staple fixation, respectively, were retrospectively reviewed. All procedures were performed using a locking spacer plate. Demographics and preoperative knee condition were similar between the groups. Clinically, the Western Ontario and McMaster Universities Arthritis Index and range of motion were evaluated preoperatively and 2 years postoperatively. Radiographically, the mechanical axis (MA), medial proximal tibial angle (MPTA), and PTS were evaluated preoperatively and within 2 years postoperatively. Hinge fractures were investigated using computed tomography at 2 weeks postoperatively. PTS loss was defined as the difference between the corresponding values at 2 weeks and 2 years postoperatively. The incidence of PTS failure (PTS loss ≥ ± 3°) was also investigated. RESULTS: The clinical results were not significantly different between groups N and S preoperatively and 2 years postoperatively. There were no significant differences in the MA, MPTA, and PTS between the groups preoperatively and 2 weeks postoperatively; changes in these variables did not differ significantly between the groups. The incidence of hinge fractures, all of which were categorized as Takeuchi type 1, did not differ significantly. PTS loss within 2 years postoperatively was significantly greater in group N than in group S (1.0° vs. 0.1°; p < 0.01). The incidence of the PTS failure was 16.5% (13/79) and 2.6% (2/77) in groups N and S, respectively (p < 0.01). CONCLUSION: Additional anteromedial staple fixation could prevent changes in the PTS in RT-OWHTO. It is a simple method for preventing an increase in the PTS after RT-OWHTO. LEVEL OF EVIDENCE: III.

Costal chondrocyte-derived pellet-type scaffold-free autologous chondrocyte implantation provided acceptable mid-term outcomes in osteochondral defects with up to 10-mm depth.

PURPOSE: To evaluate clinical, radiographic, and magnetic resonance (MR) results of costal chondrocyte-derived pellet-type scaffold-free autologous chondrocyte implantation (CCP-ACI) in osteochondral defects (ODs) up to 10-mm depth during 5 years of follow-up. METHODS: Ten patients with CCP-ACI performed in ODs with depth up to 10 mm were retrospectively analyzed. The minimum follow-up period was 5 years. The median age was 36.5 (range 20-55) years. The median size and the depth of the OD lesion were 4.25 cm2 (range 2-6) and 7.0 mm (6-9), respectively. Clinically, the International Knee Documentation Committee, Lysholm, and visual analog scale pain scores were evaluated. Radiographically, the hip‒knee‒ankle (HKA) angle and the Kellgren‒Lawrence (K‒L) grade were assessed. On MR imaging, the magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 score and the defect depth were evaluated. RESULTS: All average clinical scores improved significantly by 1, 2, and 5 years postoperatively. The average HKA angle and the proportion of K‒L grade did not change significantly within 5 years. The median total MOCART scores were 50 (range 45-65), 50 (35-90), 57.5 (40-90), and 65 (50-85) at 6 months, 1 year, 2 years, and 5 years postoperatively, respectively (p = 0.001), with significant improvement at 2 years compared to that at 6 months postoperatively. The signal intensity of the repair tissue and subchondral change significantly improved from 10 (range 10-10) to 12.5 (10-15) (p = 0.036), and from 10 (10-10) to 17.5 (0-20) (p = 0.017), respectively. Significant improvements were seen at 5 years postoperatively for the former and at 2 years postoperatively for the latter. The average depths on MR imaging were 6.7, 6.7, 6.8, 6.6, and 6.6 mm preoperatively and at 6 months, 1 year, 2 years, and 5 years postoperatively with no significant changes (n.s). CONCLUSION: CCP-ACI provided acceptable mid-term outcomes in ODs up to 10-mm in depth without bone grafting despite of no scaffold. The procedure can be one of minimally invasive treatment options for ODs without scaffold-related problems. LEVEL OF EVIDENCE: IV.

Oleic acid from cancer-associated fibroblast promotes cancer cell stemness by stearoyl-CoA desaturase under glucose-deficient condition.

BACKGROUND: Cancer-associated fibroblasts (CAFs) coordinate the malignancy of cancer cells via secretory materials. Reprogrammed lipid metabolism and signaling play critical roles in cancer biology. Oleic acid (OA) serves as a source of energy under glucose-deficient conditions, but its function in cancer progression remains unclear. The present study investigated that CAFs in xenografted tumors had higher amounts of fatty acids, particularly OA, compared to normal fibroblasts, and promoted the cancer cell stemness in lung adenocarcinoma cells under glucose-deficient condition. METHODS: Xenografts were established in immunodeficient mice by injection of NCI-H460 (H460) cells. Lipids and fatty acids were evaluated using the BODIPY staining and fatty-acid methyl esters analysis. The expression levels of markers for lipid metabolism and cancer stemness were determined by western blot, flow cytometry, and real-time PCR. Cancer cell subclones against stearoyl-CoA desaturase (SCD) were produced by lentiviral vector and CRISPR/cas9 systems. The expression of SCD was examined immunochemically in human adenocarcinoma tissues, and its clinical relevance to survival rate in lung adenocarcinoma patients was assessed by Kaplan-Meier analysis. RESULTS: Transferred CAF-derived OA through lipid transporter upregulated SCD in cancer cells under glucose-deficient conditions, resulting in enhanced lipid metabolism and autophagosome maturation. By OA treatment under glucose deficient condition, cancer cell stemness was significantly enhanced through sequential activation of SCD, F-actin polymerization and nuclear translocation of yes-associated protein. These findings were confirmed by experiments using chemical inhibitors, SCD-overexpressing cells and SCD-knockout (KO) cells. When xenografted, SCD-overexpressing cells produced larger tumors compared with parental cells, while SCD-KO cells generated much smaller tumors. Analysis of tumor tissue microarray from lung adenocarcinoma patients revealed that SCD expression was the marker for poor prognosis involving tumor grade, clinical stage and survival rate. CONCLUSION: Our data indicate that CAFs-derived OA activated lipid metabolism in lung adenocarcinoma cells under glucose-deficient conditions, subsequently enhancing stemness and progression toward malignancy.

Heterogeneous response of cancer-associated fibroblasts to the glucose deprivation through mitochondrial calcium uniporter.

Cancer-associated fibroblasts (CAFs) are an abundant component of the tumor microenvironment and have distinct features from normal fibroblasts (NFs). However, the discriminative nature of heterogeneous CAFs under glucose starvation remains unknown. In this study, we investigated the changes in the mitochondrial calcium concentration and relevant intracellular machinery in CAFs under glucose-deficient conditions. Xenografted tumor masses were dissected into multiple pieces and subjected to the CAF isolation using magnetically activated cell sorting (MACS). NFs were separated from the normal lung and skin. Under glucose starvation, CAFs from the tumor mass exhibited heterogeneity in cell proliferation, ATP production and calcium concentration. Compared to NFs, mitochondrial calcium concentration was significantly higher in glucose-starved CAFs with upregulation of mitochondrial calcium uniporter (MCU) that led to enhancement of ATP production and cell growth. Intriguingly, treatment of glucose-starved CAFs with oligomycin increased apoptosis by disrupted calcium homeostasis following overactivation of the mPTP. Moreover, oligomycin-induced apoptosis was mitigated by calcium chelation. This study demonstrated that the discriminative calcium influx to mitochondria through MCU coordinated cell growth and apoptosis in glucose-starved CAFs but not in NFs.

Calcifying aponeurotic fibroma on the paw in a dog.

A 12-year-old, spayed female, Maltese dog with a round and firm mass on the dorsal part of the left rear paw and a cervical mass was brought to the clinic. The paw mass was contiguous to the adjacent tendon; it was composed of neoplastic mesenchymal cells and had scattered foci of calcification with chondroid differentiation microscopically. The neoplastic cells were positive for vimentin and S100, but negative for desmin and smooth muscle actin. Microscopic features and immunohistochemistry results were consistent with calcifying aponeurotic fibroma (CAF). The cervical mass was composed of polygonal cells forming acini with marked anisocytosis and anisokaryosis and diagnosed as thyroid follicular carcinoma. No recurrence or metastasis occurred during follow-up. To the best of our knowledge, this is the first case of canine CAF with features identical to its human counterparts. Key clinical message: This report describes the rare case of calcifying aponeurotic fibroma on the paw in a dog. This is apparently the first case in the veterinary literature with identical clinical and pathological features to the human counterpart.

Fibrome aponévrotique calcifiant sur la patte chez un chien. Une chienne maltaise stérilisée âgée de 12 ans avec une masse ronde et ferme sur la partie dorsale de la patte arrière gauche et une masse cervicale a été amenée à la clinique. La masse de la patte était contiguë au tendon adjacent; il était composé de cellules mésenchymateuses néoplasiques et présentait des foyers de calcification dispersés avec une différenciation chondroïde au microscope. Les cellules néoplasiques étaient positives pour la vimentine et le S100, mais négatives pour la desmine et l'actine des muscles lisses. Les caractéristiques microscopiques et les résultats d'immunohistochimie étaient compatibles avec un fibrome aponévrotique calcifiant (CAF). La masse cervicale était composée de cellules polygonales formant des acini avec une anisocytose et une anisocaryose marquées et diagnostiquée comme un carcinome folliculaire de la thyroïde. Aucune récidive ou métastase n'est survenue au cours du suivi. À notre connaissance, il s'agit du premier cas de CAF canin avec des caractéristiques identiques à ses homologues humains.Message clinique clé :Ce rapport décrit le cas rare de fibrome aponévrotique calcifiant sur la patte chez un chien. C'est apparemment le premier cas dans la littérature vétérinaire avec des caractéristiques cliniques et pathologiques identiques à son homologue humain.(Traduit par Dr Serge Messier).

Thyroglobulin as a negative marker for malignancy in canine and human breast tumors.

Canine mammary gland tumors (CMTs) are the most common tumor type in female dogs. This study evaluated the expression pattern and role of thyroglobulin (Tg) in CMT and in human breast cancer (HBC). CMT samples were subjected to fine-needle aspiration, primary cell culture, and histopathology. The expression level of Tg was higher in benign CMT than in malignant CMT (mCMT) primary cells, particularly in the epithelial lineage. Moreover, treatment with Tg enhanced the sensitivity of doxorubicin in mCMT epithelial cells and mitigated proinflammatory response by increasing nuclear factor erythroid 2-related factor 2 (Nrf2). The proximal region of the Tg promoter was hypermethylated in mCMT epithelial cells, silencing Tg expression with concurrent downregulation of Nrf2-mediated antioxidant signaling. An identical pattern of Tg expression was observed in cytological and tissue samples. Tissue microarray analysis showed that Tg was highly expressed in normal and benign tissues when compared with their malignant counterparts, which was diminished along with higher histological grades. The survival rate was significantly higher in HBC patients with high Tg expression than those with low Tg expression. This study also showed that the progression of HBC is accompanied by the reduction of Tg expression along with augmentation of proinflammatory signaling. Our data suggested that Tg could be a negative indicator of malignancy in canine and human breast neoplasia.

Three-Way Junction-Induced Isothermal Amplification with High Signal-to-Background Ratio for Detection of Pathogenic Bacteria.

The consumption of water and food contaminated by pathogens is a major cause of numerous diseases and deaths globally. To control pathogen contamination and reduce the risk of illness, a system is required that can quickly detect and monitor target pathogens. We developed a simple and reproducible strategy, termed three-way junction (3WJ)-induced transcription amplification, to detect target nucleic acids by rationally combining 3WJ-induced isothermal amplification with a light-up RNA aptamer. In principle, the presence of the target nucleic acid generates a large number of light-up RNA aptamers (Spinach aptamers) through strand displacement and transcription amplification for 2 h at 37 °C. The resulting Spinach RNA aptamers specifically bind to fluorogens such as 3,5-difluoro-4-hydroxybenzylidene imidazolinone and emit a highly enhanced fluorescence signal, which is clearly distinguished from the signal emitted in the absence of the target nucleic acid. With the proposed strategy, concentrations of target nucleic acids selected from the genome of Salmonellaenterica serovar Typhi (S. Typhi) were quantitatively determined with high selectivity. In addition, the practical applicability of the method was demonstrated by performing spike-and-recovery experiments with S. Typhi in human serum.

Fluorescence nucleobase analogue-based strategy with high signal-to-noise ratio for ultrasensitive detection of food poisoning bacteria.

We developed a simple and ultrasensitive strategy for the identification of foodborne pathogens utilizing a fluorescent nucleobase analogue [2-aminopurine (2-AP)]-containing split G-quadruplex that binds blocker DNA. Compared to a previous strategy that did not use blocker DNA, this strategy showed a significant increase in the signal-to-noise ratio-by approximately 300%-owing to the displacement of the blocker DNA by the target DNA that induces the formation of an active G-quadruplex structure, thereby leading to a substantial increase in the 2-AP fluorescence signal. The proposed strategy was rationally combined with polymerase chain reaction, which resulted in the successful determination of genomic DNA (within the range of 10-106 copies) derived from the food poisoning bacterium Escherichia coli, with a limit of detection of 5.2 copies and high selectivity. In addition, the practical applicability of this method was demonstrated by analyzing E. coli-spiked lettuce samples.

Glucose starvation induces resistance to metformin through the elevation of mitochondrial multidrug resistance protein 1.

Metformin, a drug for type 2 diabetes mellitus, has shown therapeutic effects for various cancers. However, it had no beneficial effects on the survival rate of human malignant mesothelioma (HMM) patients. The present study was performed to elucidate the underlying mechanism of metformin resistance in HMM cells. Glucose-starved HMM cells had enhanced resistance to metformin, demonstrated by decreased apoptosis and autophagy and increased cell survival. These cells showed abnormalities in mitochondria, such as decreased ATP synthesis, morphological elongation, altered mitochondrial permeability transition pore and hyperpolarization of mitochondrial membrane potential (MMP). Intriguingly, Mdr1 was significantly upregulated in mitochondria but not in cell membrane. The upregulated mitochondrial Mdr1 was reversed by treatment with carbonyl cyanide m-chlorophenyl hydrazone, an MMP depolarization inducer. Furthermore, apoptosis and autophagy were increased in multidrug resistance protein 1 knockout HMM cells cultured under glucose starvation with metformin treatment. The data suggest that mitochondrial Mdr1 plays a critical role in the chemoresistance to metformin in HMM cells, which could be a potential target for improving its therapeutic efficacy.

Fluorescence polarization-based detection of cancer-related mutations using target-initiated rolling circle amplification.

We devised a new method to detect cancer-related mutations based on target-initiated rolling circle amplification in combination with fluorescence polarization. We then applied this method to identify the presence of KRAS G13D and G12D, two of the most frequent mutations found in colorectal cancer patients, demonstrating high sensitivity and specificity.

Synthesis of DNA-templated copper nanoparticles with enhanced fluorescence stability for cellular imaging.

Fluorescence of DNA-templated copper nanoparticles (DNA-CuNPs) is not stable over time which limits applications in cellular imaging. This is due to the presence of oxygen during synthesis which oxidizes Cu(0) to Cu(II) and also produces the free hydroxyl radical. The authors have prepared DNA-CuNPs with enhanced temporal stability of fluorescence by optimizing the reaction conditions so as to minimize the deleterious effects of oxygen. The operational lifetime of DNA-CuNPs was increased from 25 min to 200 min. Fluorescence spectra of DNA-CuNPs in optimized condition show an emission peak at 650 nm when excited at 340 nm. DNA-CuNPs synthesized in this manner were used for cell imaging. As a proof of concept, the nucleus of a human colon cell line (HCT116) was stained. The method does not involve any chemicals other that copper sulfate and ascorbate. This new approach for generating DNA-CuNPs improves imaging of biological processes and provides a basis for developing other types of DNA-templated nanomaterials. Graphical abstract Schematic presentation of the formation of fluorescent DNA-templated copper nanoparticles (DNA-CuNPs). A large amount of ascorbate provides long operational lifetime for cellular imaging under the condition exposed to oxygen. *Asc- and **DHA stand for ascorbate and dehydroascorbic acid.

Hypoxia promotes acquisition of aggressive phenotypes in human malignant mesothelioma.

BACKGROUND: Hypoxia is a hallmark of the solid tumor microenvironment and is associated with poor outcomes in cancer patients. The present study was performed to investigate mechanisms underlying the hypoxia-induced phenotypic changes using human malignant mesothelioma (HMM) cells. METHODS: Hypoxic conditions were achieved by incubating HMM cells in the air chamber. The effect of hypoxia on phenotype changes in HMM cells was investigated by performing in vitro clonogenicity, drug resistance, migration, and invasion assays. Signaling pathways and molecules involved in the more aggressive behaviors of HMM cells under hypoxia were investigated. A two-tailed unpaired Student's t-test or one-way ANOVA with Bonferroni post-test correction was used in this study. RESULTS: Hypoxic conditions upregulated hypoxia-inducible factor 1 alpha (HIF-1α) and HIF-2α in parallel with the upregulation of its target, Glut-1, in HMM cells. In vitro clonogenicity of HMM cells was significantly increased in hypoxic conditions, but the proliferation of cells at a high density in hypoxia was lower than that in normoxic conditions. The expression levels of HIF-2α and Oct4 were increased in hypoxic HMM cells. The percentage of cells with high CD44 expression was significantly higher in HMM cells cultured in hypoxia than those cultured in normoxia. Hypoxia significantly enhanced the resistance of HMM cells to cisplatin, which occurred through cytoprotection against cisplatin-induced apoptosis. While cisplatin treatment decreased the ratio of Bcl-2 to Bax in normoxic condition, hypoxia conversely increased the ratio in HMM cells treated with cisplatin. Hypoxia increased the mobility and invasiveness of HMM cells. Epithelial to mesenchymal transition was promoted, which was indicated by the repression of E-cadherin and the concomitant increase of vimentin in HMM cells. CONCLUSIONS: The data illustrated that hypoxic conditions augmented the aggressive phenotypes of HMM cells at the biological and molecular levels. The present study provides valuable background information beginning to understand aggressiveness of HMM in tumor microenvironments, suggesting that a control measure for tumor hypoxia may be an effective therapeutic strategy to reduce the aggressiveness of cancer cells in HMM patients.

Nickel oxide nanoparticles can recruit eosinophils in the lungs of rats by the direct release of intracellular eotaxin.

BACKGROUND: Instillation of highly soluble nanoparticles (NPs) into the lungs of rodents can cause acute eosinophilia without any previous sensitizations by the role of dissolved ions. However, whether gradually dissolving NPs can cause the same type of eosinophilia remains to be elucidated. We selected nickel oxide (NiO) as a gradually dissolving NP and evaluated the time course pulmonary inflammation pattern as well as its mechanisms. METHODS: NiO NPs were intratracheally instilled into female Wistar rats at various concentrations (50, 100, and 200 cm(2)/rat) and the lung inflammation was evaluated at various time-points (1, 2, 3, and 4 days). As positive controls, NiCl2 and the ovalbumin-induced allergic airway inflammation model was applied. NiCl2 was instilled at 171.1 µg Ni/rat, which is equivalent nickel concentration of 200 cm(2)/rat of NiO NPs. Cytological analysis and biochemical analysis including lactate dehydrogenase (LDH), total protein, and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). The levels of total immunoglobulin E (IgE) and anaphylatoxins (C3a and C5a) were measured in BALF and serum. The levels of eotaxin were measured in the alveolar macrophages and normal lung tissue before and after addition of cell lysis buffer to evaluate whether the direct lysis of cells can release intracellular eotaxin. RESULTS: NiO NPs produced acute neutrophilic inflammation throughout the study. However, eosinophils were recruited at 3 and 4 days post-instillation of NiO NPs and the magnitude and pattern of inflammation was similar with NiCl2 at 24 h post-instillation. The eosinophil recruitment by NiO NPs was not related with either the levels of total IgE or anaphylatoxins. The lysis of alveolar macrophages and normal lung tissue showed high levels of intracellular eotaxin and the levels of LDH showed positive correlation with the levels of eotaxin. CONCLUSIONS: Instillation of NiO NPs produced neutrophilia at 1 and 2 days after instillation, while the mixed type of neutrophilic and eosinophilic inflammation was produced at 3 and 4 days post-instillation, which was consistent with NiCl2. The mechanism of the eosinophilia involves the direct release of intracellular eotaxin due to the rupture of cells by the accumulated solubilized nickel ions in the phagolysosome.

Dual contribution of surface charge and protein-binding affinity to the cytotoxicity of polystyrene nanoparticles in nonphagocytic A549 cells and phagocytic THP-1 cells.

Knowledge that links the physicochemical properties of nanoparticles (NP) to their toxicity is key to evaluating and understanding mechanisms underlying toxicity and developing appropriate testing methods for NP; however, this is currently limited since only a small set of NP have been used, with typically poor control of their physical properties. In this study, eight types of polystyrene NP (PLNP) were synthesized with different functional groups, but all based on an identical core. In vitro cell-based assays were performed to determine the influence of changes in physicochemical properties, such as charge, hydrodynamic size, and protein binding potential, in relation to NP-mediated toxicity. The PLNP were incubated with nonphagocytic A549 cells or phagocytic differentiated THP-1 cells for 4 h with/without fetal bovine serum (FBS), followed by incubation for 20 h in FBS-supplemented medium with/without a washing step, to assess cell-type specificity and impact of protein corona formation. The effect of surface charge on cytotoxicity differed between A549 cells and THP-1 cells. In nonphagocytic A549 cells, the zeta potential of PLNP exhibited a negative correlation with cytotoxicity, partly due to the level of coronated protein that might affect cellular uptake. In phagocytic THP-1 cells, the zeta potential of PLNP showed a positive correlation with cytotoxicity but coronated protein levels displayed no marked association with cytotoxicity, owing to the professional uptake efficacy of phagocytic cells. The consistency of our data with THP-1 cells with the surface charge paradigm in nanotoxicology suggests that phagocytic cells are the predominant targets for lung inflammatory reactions induced by PLNP.

Similar Midterm Outcomes of Total Knee Arthroplasties with Anterior and Posterior Tibial Slopes Performed on Paired Knees at a Minimum Follow-up of 5 Years.

A small posterior tibial slope (PTS) is generally recommended in posterior stabilized (PS) total knee arthroplasty (TKA). An unwanted anterior tibial slope (ATS), which can affect postoperative results, may be created in PS TKA because of the inaccuracy of surgical instruments and techniques, as well as high interpatient variability. We compared midterm clinical and radiographic results of PS TKAs with ATS and PTS performed on paired knees using the same prosthesis. One-hundred-twenty-four patients who underwent TKAs with ATS and PTS on paired knees using ATTUNE posterior-stabilized prostheses were retrospectively reviewed after a minimum follow-up period of 5 years. The mean follow-up period was 5.4 years. The Knee Society Knee and Function scores, Western Ontario and McMaster Universities Osteoarthritis Index, Feller and Kujalar scores, and range of motion (ROM) were evaluated. The preferred TKA out of ATS and PTS was also investigated. The hip-knee-ankle angle, component positions, tibial slope, posterior femoral offset, Insall-Salvati ratio, and knee sagittal angle were measured by radiography. There were no significant differences in the clinical results, including ROM, between TKAs with ATS and PTS preoperatively and at the last follow-up. Regarding patient preference, 58 patients (46.8%) were satisfied with bilateral knees, 30 (24.2%) preferred knees with ATS, and 36 (29%) preferred knees with PTS. There was no significant difference in the rate of preference between TKAs with ATS and PTS (p = 0.539). Except for the postoperative tibial slope (-1.8 vs. 2.5 degrees, p < 0.001), there were also no significant differences in the radiographic results, including the knee sagittal angle, preoperatively and at the last follow-up. The midterm outcomes were similar between PS TKAs with ATS and PTS performed on paired knees at a minimum of 5 years of follow-up. Nonsevere ATS did not affect midterm outcomes in PS TKA with proper soft tissue balancing and the current prosthesis of improved design. However, a long-term follow-up study is required to confirm the safety of nonsevere ATS in PS TKA. LEVEL OF EVIDENCE:: III.

A Comparison of Results in Older, Middle-aged, and Younger Patients after Primary Anterior Cruciate Ligament Reconstruction: Minimum 10-Year Follow-up.

Background: Anterior cruciate ligament (ACL) reconstruction is commonly performed to prevent decreased knee function and restore stability in middle-aged and even older patients. However, few studies have compared the long-term clinical outcomes of ACL reconstruction between older, younger, and middle-aged patients. The purpose of this study was to compare the long-term clinical outcomes of ACL reconstruction in older patients with those in younger and middle-aged patients. Methods: A total of 352 patients who underwent primary ACL reconstruction between January 2003 and March 2008 were retrospectively reviewed and classified into three groups (group A: 246 [age, 20-29 years], group B: 72 [age, 40-49 years], group C: 34 [age, 50-65 years]). The mean follow-up period was 14.2 ± 1.6 years. Clinical outcomes were evaluated and compared between groups. Results: The differences in the range of motion, clinical scores, and stability tests were not statistically significant among the three groups. The difference in the graft failure rate among the three groups was significant (group A: 16 [6.5%], group B: 7 [9.7%], group C: 6 [17.6%]; p = 0.040). In particular, when compared between the two groups, there was a significant difference between group A and group C (p = 0.036). The 10-year survival rates were 93.5%, 90.3%, and 82.4% for groups A, B, and C, respectively (p = 0.048). Conclusions: Although graft failure rates were higher in older patients than younger and middle-aged patients, clinical outcomes of ACL reconstruction in older patients were comparable to those of younger and middle-aged patients in terms of the range of motion, clinical scores, and stability tests at a minimum follow-up of 10 years.

MPFL reconstruction with proximal rather than distal femoral tunnel position leads to less favorable short-term results.

BACKGROUND: This study aimed to compare the clinical and radiological outcomes of medial patellofemoral ligament (MPFL) reconstruction (MPFLR) between anatomic femoral tunnel positions: proximal (near adductor tubercle [AT]) and distal (near medial epicondyle [ME]). HYPOTHESIS: MPFLR with the proximal femoral tunnel position has worse clinical and radiological outcomes than those with the distal femoral tunnel position. PATIENTS AND METHODS: Fifty-five patients who underwent isolated MPFLR with proximal or distal femoral tunnels with at least 2 years of follow-up were retrospectively analyzed. Based on postoperative CT images, 28 patients were classified as group AT and the remaining 27 patients were classified as group ME. The International Knee Documentation Committee, Lysholm, Tegner, Kujala scores, and complications were evaluated. Radiologically, the Caton-Deschamps Index (CDI), patellar tilt angle, patellofemoral osteoarthritis (PFOA), patellofemoral cartilage status by the International Cartilage Repair Society (ICRS) grade, bone contusion, and MPFL graft signal intensity were evaluated. RESULTS: All clinical scores significantly improved in both groups (p<0.01). No statistically significant difference was noted between the two groups in regards to their preoperative demographic data, postoperative clinical scores, complications, or radiological findings (CDI, patellar tilt angle, PFOA, bone contusion, and graft signal intensity). The group AT had worse cartilage status on the medial facet of the patella (p=0.02). The ICRS grade for the medial facet of the patella statistically progressed in group AT compared to group ME (p=0.04) as well. DISCUSSION: Both groups showed significantly improved clinical outcomes. However, for the medial facet of the patella, MPFLR with the proximal femoral tunnel position had worse cartilage status and ICRS grade progression than those with the distal femoral tunnel position. LEVEL OF EVIDENCE: III; retrospective comparative study.