Clinical characteristics and management of orbital apex syndrome: a 10-year multicentre experience.

BACKGROUND: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology. METHODS: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed. RESULTS: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference. CONCLUSIONS: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Mid-term outcomes and complications of total knee arthroplasty in haemophilic arthropathy: A review of consecutive 131 knees between 2006 and 2015 in a single institute.

INTRODUCTION: Although total knee arthroplasty (TKA) in haemophilic arthropathy can reduce severe joint pain and improve functional disability, it is technically demanding. AIM: To evaluate mid-term outcomes and complications of TKA in haemophilic arthropathy. METHODS: This study retrospectively reviewed 131 consecutive primary TKAs in a single institute. The mean age was 41.0 years old, and the mean follow-up period was 6.8 years. Clinical and radiographic results were evaluated. Complications were categorized according to the classification system of the Knee Society for TKA complications. RESULTS: The average Western Ontario and McMaster Universities Arthritis Index (WOMAC) score improved from 66.0 to 24.2. The average flexion contracture significantly decreased from 17.3° to 4.7°, but the average pre- and postoperative maximum flexion did not differ (80.9° vs 85.6°, respectively). The average mechanical axis was varus 5.2° preoperatively and valgus 0.3° postoperatively. The coronal positions of the femoral and tibial components and the sagittal positions of these components were within ±3° in 83.2%, 89.3%, 63.4% and 73.3% of cases, respectively. Complications occurred in 17 knees (13.0%): hemarthrosis (n = 7), medial collateral ligament injury (n = 1), stiffness (n = 2), deep periprosthetic joint infection (PJI) (n = 3) and periprosthetic fracture (n = 4). CONCLUSIONS: The mid-term results of TKA in haemophilic arthropathy were satisfactory in pain relief, improved function and decreased flexion contracture. Bleeding and PJI continue to be major concerns for TKA in haemophilic arthropathy, and risk of periprosthetic fracture must be taken into account for patient education and appropriate prevention.

Comparison of mode of failure between primary and revision total knee arthroplasties.

INTRODUCTION: Cognizance of common reasons for failure in primary and revision TKA, together with their time course, facilitates prevention. However, there have been few reports specifically comparing modes of failure for primary vs. revision TKA using a single prosthesis. The goal of the study was to compare the survival rates, modes of failure, and time periods associated with each mode of failure, of primary vs. revision TKA. HYPOTHESIS: The survival rates, modes of failure, time period for each mode of failure, and risk factors would differ between primary and revision TKA. MATERIAL AND METHODS: Data from a consecutive cohort comprising 1606 knees (1174 patients) of primary TKA patients, and 258 knees (224 patients) of revision TKA patients, in all of whom surgery involved a P.F.C® prosthesis (Depuy, Johnson & Johnson, Warsaw, IN), was retrospectively reviewed. The mean follow-up periods of primary and revision TKAs were 9.2 and 9.8 years, respectively. RESULTS: The average 10- and 15-year survival rates for primary TKA were 96.7% (CI 95%,±0.7%) and 85.4% (CI 95%,±2.0%), and for revision TKA 91.4% (CI 95%,±2.5%) and 80.5% (CI 95%,±4.5%). Common modes of failure included polyethylene wear, loosening, and infection. The most common mode of failure was polyethylene wear in primary TKA, and infection in revision TKA. The mean periods (i.e., latencies) of polyethylene wear and loosening did not differ between primary and revision TKAs, but the mean period of infection was significantly longer for revision TKA (1.2 vs. 4.8 years, P=0.003). DISCUSSION: Survival rates decreased with time, particularly more than 10 years post-surgery, for both primary and revision TKAs. Continuous efforts are required to prevent and detect the various modes of failure during long-term follow-up. Greater attention is necessary to detect late infection-induced failure following revision TKA. LEVEL OF EVIDENCE: Case-control study, Level III.

Multi-functional magnesium alloys containing interstitial oxygen atoms.

A new class of magnesium alloys has been developed by dissolving large amounts of oxygen atoms into a magnesium lattice (Mg-O alloys). The oxygen atoms are supplied by decomposing titanium dioxide nanoparticles in a magnesium melt at 720 °C; the titanium is then completely separated out from the magnesium melt after solidification. The dissolved oxygen atoms are located at the octahedral sites of magnesium, which expand the magnesium lattice. These alloys possess ionic and metallic bonding characteristics, providing outstanding mechanical and functional properties. A Mg-O-Al casting alloy made in this fashion shows superior mechanical performance, chemical resistance to corrosion, and thermal conductivity. Furthermore, a similar Mg-O-Zn wrought alloy shows high elongation to failure (>50%) at room temperature, because the alloy plastically deforms with only multiple slips in the sub-micrometer grains (<300 nm) surrounding the larger grains (~15 µm). The metal/non-metal interstitial alloys are expected to open a new paradigm in commercial alloy design.

Synpolydactyly of the hand: a radiographic classification.

UNLABELLED: Synpolydactyly is an uncommon congenital anomaly characterized by polydactyly with syndactyly in the central hand. The purpose of this investigation was to develop and assess the reliability of a radiographic classification system for synpolydactyly. We identified 56 hands with central synpolydactyly and developed a radiographic classification system that categorizes by the location within the hand, the bony level of polydactyly, and the presence of a delta phalanx. Four paediatric hand surgeons independently reviewed each radiograph to establish reliability. There was exact agreement among raters in 40 cases (71%). The inter-rater reliability was 0.97 and intra-rater reliability was at least 0.87. Seven of 16 bilateral cases had symmetric deformity classification. The most common presentations were types 1A and 2A. We present a new, reliable radiographic classification system for synpolydactyly that will allow improved communication between clinicians and serve as a foundation for future investigations. LEVEL OF EVIDENCE: 2.

Strengthening behavior of carbon/metal nanocomposites.

Nanocomposites reinforced with nano-scale reinforcements exhibit excellent mechanical properties with low volume fraction of the reinforcement. For instance, only an addition of 0.7 vol.% few-layer graphene (FLG) into the pure titanium shows strength of ~1.5 GPa, obviously much superior to that of the monolithic titanium. The strengthening efficiency of composites is determined by several factors such as reinforcement geometrical/spatial characteristics and interfacial features between the matrix and the reinforcement. For the metal-matrix nanocomposites (MMNCs), since the nano-scale reinforcement has significantly high specific surface area, interfacial feature is more important and has to be clearly evaluated in understanding property of MMNCs. Although many researchers suggested the theoretical work using continuum mechanics in order to estimate the mechanical properties of the metallic composites, a clear determination has yet not to be proven by systematic experimental works. Here, we provide a new model to predict strength and stiffness of MMNCs based on quantitative analysis of efficiency parameters in which interface feature is strongly emphasized. To validate the model, we select multi-walled carbon nanotube (MWCNT) and FLG for reinforcement, and titanium (Ti) and aluminum (Al) for the matrix to modify bonding strength and specific surface area in the MMNCs.

Development of a genetic marker set to diagnose aspirin-exacerbated respiratory disease in a genome-wide association study.

We developed a genetic marker set of single nucleotide polymorphisms (SNPs) by summing risk scores of 14 SNPs showing a significant association with aspirin-exacerbated respiratory disease (AERD) from our previous 660 W genome-wide association data. The summed scores were higher in the AERD than in the aspirin-tolerant asthma (ATA) group (P=8.58 × 10(-37)), and were correlated with the percent decrease in forced expiratory volume in 1 s after aspirin challenge (r(2)=0.150, P=5.84 × 10(-30)). The area under the curve of the scores for AERD in the receiver operating characteristic curve was 0.821. The best cutoff value of the summed risk scores was 1.01328 (P=1.38 × 10(-32)). The sensitivity and specificity of the best scores were 64.7% and 85.0%, respectively, with 42.1% positive and 93.4% negative predictive values. The summed risk score may be used as a genetic marker with good discriminative power for distinguishing AERD from ATA.

Cellular iron uptake, trafficking and metabolism: Key molecules and mechanisms and their roles in disease.

Iron is a crucial transition metal for virtually all life. Two major destinations of iron within mammalian cells are the cytosolic iron-storage protein, ferritin, and mitochondria. In mitochondria, iron is utilized in critical anabolic pathways, including: iron-storage in mitochondrial ferritin, heme synthesis, and iron-sulfur cluster (ISC) biogenesis. Although the pathways involved in ISC synthesis in the mitochondria and cytosol have begun to be characterized, many crucial details remain unknown. In this review, we discuss major aspects of the journey of iron from its initial cellular uptake, its modes of trafficking within cells, to an overview of its downstream utilization in the cytoplasm and within mitochondria. The understanding of mitochondrial iron processing and its communication with other organelles/subcellular locations, such as the cytosol, has been elucidated by the analysis of certain diseases e.g., Friedreich's ataxia. Increased knowledge of the molecules and their mechanisms of action in iron processing pathways (e.g., ISC biogenesis) will shape the investigation of iron metabolism in human health and disease.

Ahnak functions as a tumor suppressor via modulation of TGFß/Smad signaling pathway.

We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor ß (TGFß) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFß-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFß signaling.

Intermediate-risk grouping of cervical cancer patients treated with radical hysterectomy: a Korean Gynecologic Oncology Group study.

BACKGROUND: In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy. METHODS: In total, 2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis. RESULTS: Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence. CONCLUSION: This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.

Treatment of distal femur fractures with locking plates: Comparison of periprosthetic fractures above total knee arthroplasty and non-periprosthetic fractures.

The purpose of the present study was to compare the results and plate fit of periprosthetic and non-periprosthetic distal femur fractures fixed with locking plates. Twenty-one periprosthetic fractures above a TKA and 27 non-periprosthetic fractures were retrospectively reviewed. The primary healing rate, bone union time, clinical and radiographic results, complications, and additional surgeries were compared between the two groups. The quality of the plate fit on the bone was also compared. There were no differences in the primary healing rate, bone union time, clinical and radiographic results between the two groups. The incidence of overall complication and additional surgeries did not differ (3/21 vs. 5/27, 1/21 vs. 4/27). Plate fit trouble was observed more frequently in periprosthetic fractures (10/21 vs. 1/27, p = 0.004). Fixation of distal femur fractures with locking plates provided satisfactory results with a low risk of complications and additional surgeries in both periprosthetic and non-periprosthetic fractures.

Potential risk and sodium content of children's ready-to-eat foods distributed at major amusement parks in Korea.

This study was conducted to help better understand the current sodium intake of Korean children and to establish children's good eating habits through investigation of the sodium content of ready-to-eat foods collected from nine major amusement parks in Korea. The sodium content of a total of 322 products was analysed by using ICP and then the potential risk based on the recommended daily intake of sodium as described in the Korean dietary reference intakes was determined. The results showed that sodium content was the lowest in muffins (245 mg/100 g) and the highest in seasoned dried filefish (1825 mg/100 g). The average amounts of sodium per serving of seasoned dried filefish, tteokbokki and fish paste were 1150, 1248 and 1097 mg, respectively. The values were above 50% of the daily intake of sodium recommended by the Korean dietary reference intake. The ready-to-eat foods were also classified into high, medium and low sodium content on the basis of standards recommended by the Korean Food and Drug Administration. Most snacks were classified as high sodium foods because they exceeded "300 mg (84.5% of the total daily allowance)". Furthermore, the meal substitution foods such as kimbab, tteokbokki, mandus, sandwiches and hamburgers exceeded "600 mg (90.3% of the total daily allowance)" and were also classified as high sodium foods. In addition, ready-to-eat foods in amusement parks are similar to foods eaten on streets and foods around school zones, which contain high sodium content; thus, the intake frequency might be high, which would induce high risk to children health. Koreans already consume a high amount of sodium daily via their usual diets. So, the sodium content in snacks and substitution foods needs to be reduced. Consequently, this study noted that parents and guardians should carefully consider their children's consumption of ready-to-eat foods from Korean amusement parks.

Apolipoprotein A1 potentiates lipoxin A4 synthesis and recovery of allergen-induced disrupted tight junctions in the airway epithelium.

BACKGROUND: Asthma is characterized by chronic airway inflammation triggered by various allergens in the environment. Defects in the bronchial epithelial interface with the external environment are the hallmark of asthma. Apolipoprotein A-1 (ApoA1) or ApoA1 mimetics have demonstrated anti-inflammatory activity and preventive effects in mouse models. OBJECTIVE: We investigated airway levels of ApoA1 in asthmatics and the possible role of ApoA1 in protection of the bronchial epithelium and in resolution of inflammation in cellular and animal models of asthma. METHODS: ApoA1 levels were measured in bronchoalveolar lavage fluid (BALF) from asthmatics and healthy controls. With treatment of ApoA1, mouse model of house dust mite (HDM)-driven asthma and cultured primary bronchial epithelial cells obtained from asthmatics were examined. Tight junction (TJ) expression in the bronchial epithelial cells was assessed by using confocal microscopy and immunoblot. RESULTS: Asthmatics showed significantly lower ApoA1 levels in bronchoalveolar lavage fluid than did healthy controls. Local ApoA1 treatment significantly decreased lung IL-25, IL-33, and thymic stromal lymphopoietin levels in HDM-challenged mice and inhibited allergen-induced production of these cytokines in cultured primary bronchial epithelial cells. ApoA1 promoted recovery of disrupted TJ proteins zonula occludens-1 and occludin in cultured primary bronchial epithelium obtained from asthmatics. ApoA1-induced increases in the TJ proteins were dependent on increased production of lipoxin A4 (LX A4). CONCLUSIONS AND CLINICAL RELEVANCE: ApoA1 enhances resolution of allergen-induced airway inflammation through promoting recovery of damaged TJs in the bronchial epithelium. ApoA1 could be a therapeutic strategy in chronic airway inflammatory diseases that are associated with a defective epithelial barrier, including asthma.

Exposure assessment of synthetic colours approved in Korea.

The dietary intakes of nine synthetic food colours--amaranth, erythrosine, Allura Red, Ponceau 4R, tartrazine, Sunset Yellow FCF, Fast Green FCF, Brilliant Blue FCF and indigo carmine--permitted in Korea were estimated based on food consumption data for consumers and their concentrations in processed foods. The estimated daily intakes (EDIs) by Korean consumers were compared with the acceptable daily intakes (ADIs) of the colours. Among 704 foods sampled, 471 contained synthetic colours. The most highly consumed synthetic colours were Allura Red and tartrazine; the highest EDI/ADI ratios were found for amaranth, erythrosine and Allura Red. The EDIs of infants and children were higher than those of adults. The main food categories containing colours were beverages and liquor for adults, and beverages, chocolate and ice cream for infants and children. For average Korean consumers, the EDIs were not greater than 2.5% of their corresponding ADIs, although the EDI of a conservative consumer in the upper 95th percentile reached 37% of the ADI.

ADP-ribosylation factors 1 and 6 regulate Wnt/ß-catenin signaling via control of LRP6 phosphorylation.

It has been shown that inhibition of GTPase-activating protein of ADP-ribosylation factor (Arf), ArfGAP, with a small molecule (QS11) results in synergistic activation of Wnt/ß-catenin signaling. However, the role of Arf in Wnt/ß-catenin signaling has not yet been elucidated. Here, we show that activation of Arf is essential for Wnt/ß-catenin signaling. The level of the active form of Arf (Arf-GTP) transiently increased in the presence of Wnt, and this induction event was abrogated by blocking the interaction between Wnt and Frizzled (Fzd). In addition, knockdown of Fzds, Dvls or LRP6 blocked the Wnt-mediated activation of Arf. Consistently, depletion of Arf led to inhibition of Wnt-mediated membrane PtdIns (4,5)P2 (phosphatidylinositol 4, 5-bisphosphate) synthesis and LRP6 phosphorylation. Overall, our data suggest that transient activation of Arf modulates LRP6 phosphorylation for the transduction of Wnt/ß-catenin signaling.

Identification of differentially expressed genes according to chemosensitivity in advanced ovarian serous adenocarcinomas: expression of GRIA2 predicts better survival.

BACKGROUND: The purpose of this study was to identify genes that are differentially expressed in chemosensitive serous papillary ovarian carcinomas relative to those expressed in chemoresistant tumours. METHODS: To identify novel candidate biomarkers, differences in gene expression were analysed in 26 stage IIIC/IV serous ovarian adenocarcinomas (12 chemosensitive tumours and 14 chemoresistant tumours). We subsequently investigated the immunohistochemical expression of GRIA2 in 48 independent sets of advanced ovarian serous carcinomas. RESULTS: Microarray analysis revealed a total of 57 genes that were differentially expressed in chemoresistant and chemosensitive tumours. Of the 57 genes, 39 genes were upregulated and 18 genes were downregulated in chemosensitive tumours. Five differentially expressed genes (CD36, LIFR, CHL1, GRIA2, and FCGBP) were validated by quantitative real-time PCR. The expression of GRIA2 was validated at the protein level by immunohistochemistry, and patients with GRIA2 expression showed a longer progression-free and overall survival (P=0.051 and P=0.031 respectively). CONCLUSIONS: We found 57 differentially expressed genes to distinguish between chemosensitive and chemoresistant tumours. We also demonstrated that the expression of GRIA2 among the differentially expressed genes provides better prognosis of patients with advanced serous papillary ovarian adenocarcinoma.

Prognostic significance of MRI-detected bladder muscle and/or serosal invasion in patients with cervical cancer treated with radiotherapy.

In cervical cancer, the prognostic significance of bladder wall invasion on MRI without pathological evidence of mucosal invasion is not known. From 454 consecutive patients with cervical cancer who were treated with radiation, we reviewed images and analysed the outcome of 92 patients with the Federation of International Gynecology and Obstetrics (FIGO) stage IIIB-IVA. We analysed the patients in three groups, normal, wall (muscle and/or serosal) invasion and mucosal invasion, according to the findings on the MRI. Kaplan-Meier life table analysis and the log-rank test were used to assess the survival rates and differences according to prognostic factors. MRI detected abnormalities in the bladder wall in 42 patients (45.6%): wall invasion in 24 and mucosal invasion in 18. 5 of 18 patients, suspected on MRI to have mucosal invasion, showed no pathological evidence of mucosal invasion. Median follow-up period was 34 months. 3-year cause-specific survival (CSS) in the normal group compared with the wall invasion group was 76.2% vs 71.4% (p = 0.48). 3-year CSS for the wall invasion group compared with the mucosal invasion group was 71.4% vs 54.3% (p = 0.04). Mucosal invasion on MRI (p = 0.03) and concurrent chemoradiotherapy (p = 0.01) was significant for CSS. The prognosis for patients with cervical cancer with evidence of muscle and/or serosal invasion of the bladder on MRI may not differ from that for patients without abnormality on MRI. In patients with the MRI finding of bladder mucosal invasion, further studies should be conducted regarding the role of cystoscopy to determine the need for pathological confirmation.

Closed-wedge high tibial osteotomy using computer-assisted surgery compared to the conventional technique.

We assessed the reliability, accuracy and variability of closed-wedge high tibial osteotomy (HTO) using computer-assisted surgery compared to the conventional technique. A total of 50 closed-wedge HTO procedures were performed using the navigation system, and compared with 50 HTOs that had been performed with the conventional technique. In the navigation group, the mean mechanical axis prior to osteotomy was varus 8.2 degrees, and the mean mechanical axis following fixation was valgus 3.6 degrees. On the radiographs the mean pre-operative mechanical axis was varus 7.3 degrees, and the mean post-operative mechanical axis was valgus 2.1 degrees . There was a positive correlation between the measured data taken under navigation and by radiographs (r > 0.3, p < 0.05). The mean correction angle was significantly more accurate in the navigation group (p < 0.002). The variability of the correction was significantly lower in the navigation group (2.3 degrees vs 3.7 degrees , p = 0,012). We conclude that navigation provides reliable real-time intra-operative information, may increase accuracy, and improves the precision of a closed-wedge HTO.

Technical note: a gene delivery system in the embryonic cells of avian species using a human adenoviral vector.

Adenovirus (Ad) has been used in vivo and in vitro as a vector to carry a foreign gene for efficient gene delivery into various cell types and tissues of animals. The aim of the current study was to evaluate the Ad delivery system in primary avian cells. Primary cells isolated from the embryonic pectoralis major muscles of the chicken and quail were cultured and incubated with human recombinant Ad serotype 5 (Ad5) containing sequences encoding either the green fluorescence protein (GFP) gene alone, as a tracking marker, or both GFP and murine 3-hydroxyisobutyryl-CoA hydrolase (mHIBCH) as a target gene. The fluorescent GFP images showed the successful delivery of a target gene using Ad5 in the primary avian cultured cells. In addition, immunostaining of the myosin heavy chain (MyHC) in these cells indicated that a large population of the cells was myogenic. Colocalization of GFP-positive cells with MyHC staining was mostly found in MyHC-negative cells, indicating successful delivery of Ad5 into a large population of mononucleated cells. Furthermore, the current fluorescence study detected the dual expression of GFP and mHIBCH protein in GFP-positive cells. Finally, Western blot analysis confirmed that the Ad-mediated expression of mHIBCH protein was specific in primary cultures of avian myogenic cells and that the mHIBCH protein expression was continued for 15 d after infection in chicken primary cells. These data demonstrate that Ad5 is a feasible tool to express foreign genes in primary cultured cells of avian species, providing a new approach to study the function of genes of interest in muscle development and metabolism.