Comparison of Anterior-Stabilized and Posterior-Stabilized Total Knee Arthroplasty in the Same Patients: A Prospective Randomized Study.

BACKGROUND: A highly conforming, anterior-stabilized (AS) insert is designed to provide anteroposterior (AP) stability of the posterior-stabilized (PS) insert without a post. The purpose of this study was to compare the static and dynamic stability and function of AS and PS total knee arthroplasty (TKA) in the same patients. METHODS: A prospective, randomized controlled trial was performed in 45 patients scheduled to undergo same-day bilateral TKA. One knee was randomly assigned to receive an AS TKA, and the other knee was scheduled for a PS TKA from the same knee system. At 2 years postoperatively, the static AP stability was compared using anterior and posterior drawer stress radiographs at 90° knee flexion. Dynamic AP stability was evaluated using one-leg standing lateral fluoroscopic images throughout the range of motion. Knee function was compared using the Knee Society Score and Western Ontario and McMaster Universities Osteoarthritis Index score. RESULTS: At 2 years postoperatively, there was a significant difference in knee AP laxity at 90° of flexion between the two groups (7.6 ± 3.9 mm in the AS group vs 2.2 ± 2.3 in the PS group, P < .001). However, there were no differences in dynamic AP stability under one-leg standing fluoroscopic lateral images at 30°, 60°, and 90° knee flexion (P = .732, P = .764, and P = .679, respectively). The Knee Society Score and Western Ontario and McMaster Universities Osteoarthritis Index scores were not significantly different between the two groups (P = .641 and P = .582, respectively). CONCLUSION: Despite the fact that the AS TKA group showed significantly more static posterior displacement than the PS TKA group at 90° of knee flexion, both the AS and PS TKA groups showed similar dynamic stability under weight-bearing conditions and knee function at 2 years postoperatively.

Is Routine Thromboprophylaxis Needed in Korean Patients Undergoing Unicompartmental Knee Arthroplasty?

This study was undertaken to determine the prevalence and the natural course of venous thromboembolism (VTE) without thromboprophylaxis to ascertain whether routine thromboprophylaxis is necessary following unicompartmental knee arthroplasty (UKA) in Korean patients. The medical records and multidetector row computed tomography (MDCT) imaging of the consecutive 77 UKAs in 70 patients were reviewed. In all patients, MDCTs were undertaken preoperatively and at 1-week after surgery, and VTE symptoms were evaluated. At postoperative 6-months, follow-up MDCTs were undertaken in all patients in whom VTEs were newly detected after surgery. VTE lesions were newly detected in 18 (26%) of the 70 patients. However, none of the patients complained of VTE-related symptoms and MDCT demonstrated that all VTEs were small and involved limited portion without lower leg edema or pleuroparenchymal complication. At the 6-month follow up MDCT, all types of VTEs were shown to be completely resolved, regardless of their location. All of the VTE lesions maintained an asymptomatic status for 6-month after surgery. VTE following UKA in Korean patients who do not receive thromboprophylaxis seems to occur frequently, but all of the VTEs are clinically insignificant and all VTEs are spontaneously regressed. Routine thromboprophylaxis or thrombolytic treatment in Korean patients undergoing UKA may not be necessary.

Surgical treatment of lesions of the long head of the biceps brachii tendon with rotator cuff tear: a prospective randomized clinical trial comparing the clinical results of tenotomy and tenodesis.

BACKGROUND: Tenotomy and tenodesis are common treatments for lesions in the long head of biceps tendon (LHBT); however, which treatment is superior is still controversial. This study compared the outcomes of tenotomy with outcomes of tenodesis for treatment of LHBT lesions with rotator cuff tears. METHODS: The study enrolled 128 patients with LHBT lesions and small- to medium-sized rotator cuff tear. Arthroscopic LHBT tenotomy was done in 56 patients (group I), and LHBT tenodesis was done for 72 patients (group II) with rotator cuff repair. American Shoulder and Elbow Surgeons Score, simple shoulder test, pain visual analog scale, range of motion, and cosmetic changes were assessed initially, at 3, 6, and 12 months postoperatively, and the last visit. The elbow motor power and magnetic resonance imaging were evaluated at 12 months. RESULTS: Both groups showed improvement in functional scores after treatments, but no significant difference was found between the 2 groups at each assessment. The rate of Popeye deformity was 3 times higher in group I (P = .04). Group II showed greater forearm supination power than group I (P = .02). On magnetic resonance imaging, 45 patients (80.4%) in group I showed maintenance of the LHBT cut end within the bicipital groove, whereas 65 patients (90.3%) in group II showed maintenance of fixated LHBT. CONCLUSION: For the treatment of LHBT lesions with rotator cuff tear, patients with tenotomy and tenodesis both showed significant improvements in functional scores. The incidence of Popeye deformity was about 3-times higher in tenotomy group. No significant differences in elbow motor power were observed except greater forearm supination power in the tenodesis group.

Biocompatibility and proteomic profiling of DMSA-coated iron nanocubes in a human glioblastoma cell line.

Background: Superparamagnetic iron core iron oxide shell nanocubes have previously shown superior performance in magnetic resonance imaging T2 contrast enhancement compared with spherical nanoparticles. Methods: Iron core iron oxide shell nanocubes were synthesized, stabilized with dimercaptosuccinic acid (DMSA-NC) and physicochemically characterized. MRI contrast enhancement and biocompatibility were assessed in vitro. Results: DMSA-NC showed a transverse relaxivity of 122.59 mM-1·s-1 Fe. Treatment with DMSA-NC did not induce cytotoxicity or oxidative stress in U-251 cells, and electron microscopy demonstrated DMSA-NC localization within endosomes and lysosomes in cells following internalization. Global proteomics revealed dysregulation of iron storage, transport, transcription and mRNA processing proteins. Conclusion: DMSA-NC is a promising T2 MRI contrast agent which, in this preliminary investigation, demonstrates favorable biocompatibility with an astrocyte cell model.

MRI is a powerful tool used in the diagnosis of cancer, strokes and other injuries. An MRI scan can be improved with the use of iron oxide nanoparticles, which enhance the contrast of the image. In this study we have developed cube-shaped iron nanoparticles (nanocubes), which have been previously shown to be more effective at inducing contrast. We demonstrated that iron-based nanocubes do not damage or induce stress in cells and work effectively as an MRI contrast agent. We further analyzed how the nanocubes may affect cell functioning by investigating changes to protein levels in the cells. The results of this study are promising steps towards using iron-based nanocubes as a tool to improve the clarity of MRI scans for medical imaging and diagnosis. Future work must determine whether these nanocubes work effectively and safely in an animal model, which is a critical step in progressing to their use in clinical settings.

Evaluation of Dimercaptosuccinic Acid-Coated Iron Nanoparticles Immunotargeted to Amyloid Beta as MRI Contrast Agents for the Diagnosis of Alzheimer's Disease.

Nanoparticle-based magnetic contrast agents have opened the potential for magnetic resonance imaging (MRI) to be used for early non-invasive diagnosis of Alzheimer's disease (AD). Accumulation of amyloid pathology in the brain has shown association with cognitive decline and tauopathy; hence, it is an effective biomarker for the early detection of AD. The aim of this study was to develop a biocompatible magnetic nanoparticle targeted to amyloid beta (Aß) plaques to increase the sensitivity of T2-weighted MRI for imaging of amyloid pathology in AD. We presented novel iron core-iron oxide nanoparticles stabilized with a dimercaptosuccinic acid coating and functionalized with an anti-Aß antibody. Nanoparticle biocompatibility and cellular internalization were evaluated in vitro in U-251 glioblastoma cells using cellular assays, proteomics, and transmission electron microscopy. Iron nanoparticles demonstrated no significant in vitro cytotoxicity, and electron microscopy results showed their movement through the endocytic cycle within the cell over a 24 h period. In addition, immunostaining and bio-layer interferometry confirmed the targeted nanoparticle's binding affinity to amyloid species. The iron nanoparticles demonstrated favourable MRI contrast enhancement; however, the addition of the antibody resulted in a reduction in the relaxivity of the particles. The present work shows promising preliminary results in the development of a targeted non-invasive method of early AD diagnosis using contrast-enhanced MRI.

Recent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?

Owing to the global exponential increase in population ageing, there is an urgent unmet need to develop reliable strategies to slow down and delay the ageing process. Age-related neurodegenerative diseases are among the main causes of morbidity and mortality in our contemporary society and represent a major socio-economic burden. There are several controversial factors that are thought to play a causal role in brain ageing which are continuously being examined in experimental models. Among them are oxidative stress and brain inflammation which are empirical to brain ageing. Although some candidate drugs have been developed which reduce the ageing phenotype, their clinical translation is limited. There are several strategies currently in development to improve brain ageing. These include strategies such as caloric restriction, ketogenic diet, promotion of cellular nicotinamide adenine dinucleotide (NAD+) levels, removal of senescent cells, 'young blood' transfusions, enhancement of adult neurogenesis, stem cell therapy, vascular risk reduction, and non-pharmacological lifestyle strategies. Several studies have shown that these strategies can not only improve brain ageing by attenuating age-related neurodegenerative disease mechanisms, but also maintain cognitive function in a variety of pre-clinical experimental murine models. However, clinical evidence is limited and many of these strategies are awaiting findings from large-scale clinical trials which are nascent in the current literature. Further studies are needed to determine their long-term efficacy and lack of adverse effects in various tissues and organs to gain a greater understanding of their potential beneficial effects on brain ageing and health span in humans.

Intravenous Ferric Carboxymaltose Improves Response to Postoperative Anemia Following Total Knee Arthroplasty: A Prospective Randomized Controlled Trial in Asian Cohort.

Background: Ferric carboxymaltose (FCM) is an intravenous (IV) high-dose iron that is effective in the treatment of iron deficiency anemia. This study was performed to determine whether postoperative FCM infusion is effective at improving hemoglobin (Hb) responders, Hb and iron profiles, and the patient's quality of life (QOL). Methods: A total of 110 patients with postoperative anemia, defined by a Hb < 10 g/dL within 3 days of unilateral primary TKA, between June 2018 and February 2020 were randomized into either the FCM or Control group. On postoperative day 3, the FCM group (55 patients) received IV FCM while the Control group (55 patients) did not. The Hb responders (Hb increase ≥ 2 g/dL compared to baseline), Hb level, iron profiles (ferritin, total iron-binding capacity (TIBC), transferrin saturation (TSAT)), and EQ-5D scores were compared at weeks 2, 4, and 8. Results: The FCM group demonstrated a significantly greater number of Hb responders (p < 0.001) and a higher Hb level (p = 0.008) at 2 weeks postoperative than did the Control group. The FCM group recovered its preoperative Hb level between 4 and 8 weeks. In contrast, the Control group did not recover its preoperative level until 8 weeks. The FCM infusion group also had higher serum ferritin, iron and TSAT, and lower TIBC levels than those of the Control group between 2 and 8 weeks (all p < 0.001). However, there was no significant difference in the postoperative transfusion rate (p = 0.741) or EQ-5D score between the two groups (all p > 0.05). Discussion: In postoperative anemia following TKA, IV FCM increases the Hb response and improves Hb and iron metabolism variables, however, it does not affect the transfusion rate or QOL.

Effects of allergic rhinitis on the progression and recovery of acute otitis media in a mouse model.

OBJECTIVES: The objective of this study was to evaluate the effects of allergic rhinitis (AR) on the development, progression, and recovery of acute otitis media (OM) in an animal model and investigate the secondary effects of bacterial infection. METHODS: BALB/c mice were divided into four groups: AR + OM, AR, OM, and control groups. AR + OM and AR groups were sensitized with ovalbumin (OVA) and alum and then challenged intranasally with OVA. Phosphate-buffered saline (PBS) was administered to the OM and control groups the same number of times. After AR induction, OM was induced by surgical inoculation of non-typeable Haemophilus influenza (NTHi) into the middle ear (ME) cavity of the mice in the AR + OM and OM groups. PBS was injected into the bulla in the AR and control groups. Each group was subdivided into sets of six mice, one for each of the four time points (0, 2, 7, and 10 days post-bacterial inoculation), at which point the mice were euthanized and ME and nasal cavity mucosa were obtained and evaluated. The occurrence of OM and the ME mucosa thickness were evaluated and compared among the four groups. Tissue expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in infected ME mucosa was assessed by immunohistochemical staining. We also investigated IgE, IL-4, and IL-5 in the nasal mucosa. RESULTS: Most of the ears showed OM on post-inoculation day 2 in both AR + OM and OM groups. In the AR + OM group, 58.3% of ears still had OM on post-inoculation day 10, while only 16.7% of the OM group had OM. The ME mucosa of all groups increased, and the AR + OM group exhibited the thickest mucosa. The OM group showed peak thickness on post-inoculation day 2 and then decreased, whereas the ME mucosa thickness of the AR + OM group continued to increase to day 7. In the OM group, the expression of IL-1ß, IL-6, and TNF-α in the ME also increased significantly, peaking on post-inoculation day 2, and then gradually decreased. In the AR + OM group, the expression of these proteins increased until day 7 and then decreased. The IgE and Th2 response (IL-4 and IL-5) cytokines were expressed at higher levels in the AR + OM and AR groups than in the OM and control groups. CONCLUSION: The inflammatory reaction to NTHi was more intense and lasted longer in the allergic group, which indicates that AR affects the progression and subsequent recovery of acute bacterial OM.

Feasibility and Advantages of Full Thickness Skin Graft from the Anterolateral Thigh.

BACKGROUND: Full thickness skin graft (FTSG) gives better outcomes than split thickness skin graft (STSG), but it has the drawback of limited donor sites. Anterolateral thigh (ALT), a popular donor site of STSG, is also a popular donor site of perforator flaps. This area has the advantage of large flap size available with primary closure. Based on this we harvested FTSG instead of STSG from the ALT. METHODS: We retrospectively reviewed 10 cases of FTSG from the ALT, with the recipient site of foot in 3, ankle in 2, lower leg in 2, forearm in 2, and wrist in 1 patient. In all cases elliptical full thickness skin was harvested from the ALT, and the donor site was closed primarily. The skin was defatted and placed onto the defect with vacuum-assisted closure (VAC). The skin size ranged 7-30 cm in length and 3-12 cm in width. Mean follow up period was 7 months (range, 3-13). RESULTS: FTSG from the ALT provided durable wound coverage, with excellent color and texture matching. Partial (< 20%) graft failure was observed in 1 case, but no additional surgery was necessary. No patient reported donor site pain at postoperative 2 weeks. No donor site complications were encountered. No patient complained a feeling of tension in the thigh at final follow-up. CONCLUSIONS: FTSG from the ALT is feasible with the aid of VAC. Considering the skin quality, large skin size available, early pain relief, and little donor site morbidity, the ALT should be revisited as a donor site of FTSG.

Pseudarthrosis Repair Using Autologous Cultured Osteoblasts in Complex Type-1 Neurofibromatosis Spinal Deformity: A Case Report and Review of the Literature.

STUDY DESIGN: A case report and literature review. OBJECTIVE: To report a late dislocation of the vertebra caused by progressive dural ectasia combined with type-1 neurofibromatosis (NF-1) and the clinical results of pseudarthrosis repairs using autologous cultured osteoblasts. SUMMARY OF BACKGROUND DATA: NF-1 is a well-known genetic disorder that is commonly characterized by spinal deformities including kyphoscoliosis. Late dislocation of the vertebra resulting from progressive dural ectasia after surgical correction of NF-1 scoliosis is a very rare occurrence, and pseudarthrosis frequently develops after surgical intervention for this complex spinal deformity. METHODS: A 32-year-old female patient with NF-1 scoliosis underwent surgical correction with posterior instrumented fusion. Seventeen years later, dislocation of the lumbar spine with implant failure resulting from massive progressive dural ectasia was observed. She underwent anterior interbody fusion three times and posterior instrumented fusion four times for pseudarthrosis followed by surgical deformity correction. For the last operation, autologous cultured osteoblasts were used as a therapeutic approach to repair the pseudarthrosis, and a three-dimensional printing technique was used to understand the surgical anatomy of the dislocated lumbar spine in detail. RESULTS: After the final operation, bone union was achieved and confirmed by clinical and radiological examination. CONCLUSION: Spine surgeons should be knowledgeable about the possibility of late destabilization of the spine, due to pulsatile dural ectasia, and a high rate of pseudarthrosis in neurofibromatosis. Autologous cultured osteoblasts may prove to be a modality that can be applied pseudarthrosis repair to treat complex spinal deformity. LEVEL OF EVIDENCE: 5.

Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model.

Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo.

Physiological difference between dietary obesity-susceptible and obesity-resistant Sprague Dawley rats in response to moderate high fat diet.

The primary aim of the present study was to define central and peripheral physiological differences between dietary obesity-susceptible (DOS) and obesity-resistant (DOR) outbred Sprague Dawley (SD) rats when given a moderate high fat diet containing 32.34% of energy as a fat. After a 9-week feeding period, the DOS-SD rats consumed significantly more feed (11.1%) and had higher abdominal (39.9%) and epididymal (27.5%) fat pads than the DOR-SD rats. In addition, serum leptin and insulin levels were significantly increased in the DOS-SD rats compared with those in the DOR-SD rats. However, we did not observe significant differences in serum triglyceride, cholesterol and glucose. No differences in hypothalamic OB-Ra and Rb mRNA expressions were found between the two groups. In contrast, arcuate NPY immunohistochemical expression was much higher in the DOS-SD rats than in the DOR-SD rats, though NPY expression in the supraoptic and paraventricular nuclei was not different between the two phenotypes. In peripheral tissues, the DOS-SD rats showed noticeably increased acetyl CoA carboxylase (ACC) mRNA expression in the liver, not epididymal fat. However, Western blot of peroxisomal proliferator activated factor gamma (PPAR gamma) in the liver and epididymal fat was not different between the two phenotypes of SD rats. It was concluded that different body weight phenotypes within outbred SD population responded differently to the development of dietary induced obesity via altered anabolic features in the hypothalamus and liver.

Acanthopanax sessiliflorus stem confers increased resistance to environmental stresses and lifespan extension in Caenorhabditis elegans.

BACKGROUND/OBJECTIVES: Acanthopanax sessiliflorus is a native Korean plant and used as traditional medicine or an ingredient in many Korean foods. The free radical theory of aging suggests that cellular oxidative stress caused by free radicals is the main cause of aging. Free radicals can be removed by cellular anti-oxidants. MATERIALS/METHODS: Here, we examined the anti-oxidant activity of Acanthopanax sessiliflorus extract both in vitro and in vivo. Survival of nematode C. elegans under stress conditions was also compared between control and Acanthopanax sessiliflorus extract-treated groups. Then, anti-aging effect of Acanthopanax sessiliflorus extract was monitored in C. elegans. RESULTS: Stem extract significantly reduced oxidative DNA damage in lymphocyte, which was not observed by leaves or root extract. Survival of C. elegans under oxidative-stress conditions was significantly enhanced by Acanthopanax sessiliflorus stem extract. In addition, Acanthopanax sessiliflorus stem increased resistance to other environmental stresses, including heat shock and ultraviolet irradiation. Treatment with Acanthopanax sessiliflorus stem extract significantly extended both mean and maximum lifespan in C. elegans. However, fertility was not affected by Acanthopanax sessiliflorus stem. CONCLUSION: Different parts of Acanthopanax sessiliflorus have different bioactivities and stem extract have strong anti-oxidant activity in both rat lymphocytes and C. elegans, and conferred a longevity phenotype without reduced reproduction in C. elegans, which provides conclusive evidence to support the free radical theory of aging.

Neuroprotective effect of a new synthetic aspirin-decursinol adduct in experimental animal models of ischemic stroke.

Stroke is the second leading cause of death. Experimental animal models of cerebral ischemia are widely used for researching mechanisms of ischemic damage and developing new drugs for the prevention and treatment of stroke. The present study aimed to comparatively investigate neuroprotective effects of aspirin (ASA), decursinol (DA) and new synthetic aspirin-decursinol adduct (ASA-DA) against transient focal and global cerebral ischemic damage. We found that treatment with 20 mg/kg, not 10 mg/kg, ASA-DA protected against ischemia-induced neuronal death after transient focal and global ischemic damage, and its neuroprotective effect was much better than that of ASA or DA alone. In addition, 20 mg/kg ASA-DA treatment reduced the ischemia-induced gliosis and maintained antioxidants levels in the corresponding injury regions. In brief, ASA-DA, a new synthetic drug, dramatically protected neurons from ischemic damage, and neuroprotective effects of ASA-DA may be closely related to the attenuation of ischemia-induced gliosis and maintenance of antioxidants.