Effect of Sevoflurane Anesthesia on Diastolic Function: A Prospective Observational Study.

BACKGROUND: The effect of sevoflurane on left ventricular diastolic function is not well understood. We hypothesized that parameters of diastolic function may improve under sevoflurane anesthesia in patients with preexisting diastolic dysfunction compared to patients with normal diastolic function. METHODS: This observational study included 60 patients undergoing breast surgery or laparoscopic cholecystectomy. Patients were assigned to diastolic dysfunction (n = 34) or normal (n = 26) groups of septal e' < 8 or ≥ 8.0 cm/s on the first thoracic echocardiography (TTE) performed before anesthesia. During anesthesia, sevoflurane was maintained at 1 to 2 minimum alveolar concentration (MAC) to maintain the bispectral index at 40 to 50. At the end of surgery, the second TTE was performed under 0.8 to 1 MAC of sevoflurane with the patient breathing spontaneously without ventilator support. Primary end point was the percentage change (Δ) of e' on 2 TTEs (Δe'). Secondary end points were ΔE/e', Δleft atrial volume index (ΔLAVI), and Δtricuspid regurgitation maximum velocity (ΔTR Vmax). These percentage changes (Δ) were compared between diastolic dysfunction and normal groups. RESULTS: e' (Δe': 30 [6, 64] vs 0 [-18, 11]%; P < .001), mitral inflow E wave velocity (E), mitral inflow E/A ratio (E/A), and mitral E velocity deceleration time (DT) improved significantly in diastolic dysfunction group compared to normal group. LAVI decreased in diastolic dysfunction group but did not reach statistical significance between the 2 groups (ΔLAVI:-15 [-31, -3] vs -4 [-20, 10]%, P = .091). ΔE/e' was not different between the 2 groups (11 [-16, 26] vs 12 [-9, 22]%, P = .853) (all: median [interquartile range, IQR]). TR was minimal in both groups. CONCLUSIONS: In this study, echocardiographic parameters of diastolic function, including septal e', E, E/A, and DT, improved with sevoflurane anesthesia in patients with preexisting diastolic dysfunction, but remained unchanged in patients with normal diastolic function.

IgSF11 deficiency alleviates osteoarthritis in mice by suppressing early subchondral bone changes.

Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and is thus also accompanied by local inflammation, subchondral bone changes, and persistent pain. However, our understanding of the underlying subchondral bone dynamics during OA progression is poor. Here, we demonstrate the contribution of immunoglobulin superfamily 11 (IgSF11) to OA subchondral bone remodeling by using a murine model. In particular, IgSF11 was quickly expressed by differentiating osteoclasts and upregulated in subchondral bone soon after destabilization-of-the-medial-meniscus (DMM)-induced OA. In mice, IgSF11 deficiency not only suppressed subchondral bone changes in OA but also blocked cartilage destruction. The IgSF11-expressing cells in OA subchondral bone were found to be involved in osteoclast maturation and bone resorption and colocalized with receptor-activator of nuclear-factor κ-B (RANK), the key osteoclast differentiation factor. Thus, our study shows that blocking early subchondral bone changes in OA can ameliorate articular cartilage destruction in OA.

Development of Anti-OSCAR Antibodies for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease that causes local inflammation and pain, significantly reducing the quality of life and normal social activities of patients. Currently, there are no disease-modifying OA drugs (DMOADs) available, and treatment relies on pain relief agents or arthroplasty. To address this significant unmet medical need, we aimed to develop monoclonal antibodies that can block the osteoclast-associated receptor (OSCAR). Our recent study has revealed the importance of OSCAR in OA pathogenesis as a novel catabolic regulator that induces chondrocyte apoptosis and accelerates articular cartilage destruction. It was also shown that blocking OSCAR with a soluble OSCAR decoy receptor ameliorated OA in animal models. In this study, OSCAR-neutralizing monoclonal antibodies were isolated and optimized by phage display. These antibodies bind to and directly neutralize OSCAR, unlike the decoy receptor, which binds to the ubiquitously expressed collagen and may result in reduced efficacy or deleterious off-target effects. The DMOAD potential of the anti-OSCAR antibodies was assessed with in vitro cell-based assays and an in vivo OA model. The results demonstrated that the anti-OSCAR antibodies significantly reduced cartilage destruction and other OA signs, such as subchondral bone plate sclerosis and loss of hyaline cartilage. Hence, blocking OSCAR with a monoclonal antibody could be a promising treatment strategy for OA.

Roles of osteoclast-associated receptor in rheumatoid arthritis and osteoarthritis.

Osteoclast-associated receptor (OSCAR) is a member of the leukocyte receptor complex (LRC)-encoded protein family, which is characterized by the presence of immunoglobulin (Ig)-like domains. OSCAR recognizes collagen and was first identified as a co-stimulatory receptor that is needed for complete osteoclast differentiation. However, it is now clear that OSCAR is also expressed by multiple immune cells that participate in many innate and adaptive immune cell activities. We also showed recently that chondrocytes express OSCAR. Our and other studies suggest that OSCAR participates in the pathogenesis of two common joint diseases, namely, rheumatoid arthritis (RA) and osteoarthritis (OA). Specifically, OSCAR promotes osteoclast formation and therefore bone erosion in RA while in OA, it triggers chondrocyte death, thereby inducing cartilage fragility. Significantly, blocking the interaction of OSCAR with its collagen ligand can markedly reduce these activities in vitro and in vivo. Thus, this novel approach may have therapeutic potential for joint diseases.

Antiobesity therapeutics with complementary dual-agonist activities at glucagon and glucagon-like peptide 1 receptors.

AIM: To develop more effective and long-lasting antiobesity and antidiabetic therapeutics by employing novel chemical modifications of glucagon-like peptide-1 receptor (GLP-1R) agonists. METHODS: We constructed novel unimolecular dual agonists of GLP-1R and glucagon receptor prepared by linking sEx-4 and native glucagon (GCG) via lysine or triazole [sEx4-GCG(K) and sEx4-GCG(T), respectively] and evaluated their antiobesity and antidiabetic efficacy in the diabetic and obese mouse model. RESULTS: Both sEx4-GCG(K) and sEx4-GCG(T) showed the beneficial metabolic effects of GLP-1 and glucagon: they promoted weight loss and ameliorated insulin resistance and hepatic steatosis. They also increased thermogenesis in brown adipose tissue, and lipolysis and ß-oxidation in white adipose tissue, with concomitant suppression of lipogenesis. Furthermore, both dual agonists activated the 5'-AMP-activated protein kinase signalling pathway and prevented palmitate-induced oxidative stress in skeletal muscle cells. CONCLUSION: Through their complementary dual agonism, sEx4-GCG(T) and sEx4-GCG(K) induce more marked weight loss and metabolic improvements than conventional agonists, and could be developed as novel therapeutic agents for the treatment of obesity and associated metabolic disorders in humans.

Comparison of noise-optimized linearly blended images and noise-optimized virtual monoenergetic images evaluated by dual-source, dual-energy CT in cardiac vein assessment.

BACKGROUND: The coronary venous system is frequently used as an entry route to the heart and treatment modalities for many cardiac diseases and many procedures. Consequently, evaluation of the coronary venous system and understanding cardiac vein anatomy is crucial. PURPOSE: To determine the optimal image set in a comparison of noise-optimized linearly blended images (F_0.6) and noise-optimized virtual monoenergetic images (VMI+) evaluated by dual-energy computed tomography (DECT) for cardiac vein assessment. MATERIAL AND METHODS: Thirty-four patients (mean age 58.2 ± 14.2 years) who underwent DECT due to chest pain were enrolled. Images were post-processed with the F_0.6, and VMI+ algorithms at energy levels in the range of 40-100 keV in 10-keV increments. Enhancement (HU), noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were objectively measured at two points in the great cardiac vein by consensus of two radiologists. Two blinded observers evaluated the subjective image quality of the great cardiac vein on a 4-point scale. RESULTS: HU, noise, and SNR peaked at 40 keV VMI+ (P < 0.05) among 50-100 keV VMI+. CNR peaked at 100 keV VMI+; however, there were no significant differences compared to CNR images processed at 40-90 keV VMI+. HU and noise were significantly higher in 40 keV VMI+ than F_0.6 images; however, both SNR and CNR were significantly higher in F_0.6 images. An assessment of subjective vein delineation revealed that F_0.6 images had the highest scores. CONCLUSION: F_0.6 images were superior to VMI+ and provided the optimal image set for cardiac vein assessment.

Osteoclast-associated receptor blockade prevents articular cartilage destruction via chondrocyte apoptosis regulation.

Osteoarthritis (OA), primarily characterized by articular cartilage destruction, is the most common form of age-related degenerative whole-joint disease. No disease-modifying treatments for OA are currently available. Although OA is primarily characterized by cartilage destruction, our understanding of the processes controlling OA progression is poor. Here, we report the association of OA with increased levels of osteoclast-associated receptor (OSCAR), an immunoglobulin-like collagen-recognition receptor. In mice, OSCAR deletion abrogates OA manifestations, such as articular cartilage destruction, subchondral bone sclerosis, and hyaline cartilage loss. These effects are a result of decreased chondrocyte apoptosis, which is caused by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in induced OA. Treatments with human OSCAR-Fc fusion protein attenuates OA pathogenesis caused by experimental OA. Thus, this work highlights the function of OSCAR as a catabolic regulator of OA pathogenesis, indicating that OSCAR blockade is a potential therapy for OA.

Low-Temperature Oxidation Reactivity of Low-Rank Coals and Their Petrographic Properties.

Through the oxidation of coal at low temperatures and the resulting petrographic analysis, this study aims to predict spontaneous combustion, which has emerged as an industrial problem. Low-temperature oxidation analysis and the corresponding petrographic characteristics of four different coals treated under low temperatures of 25, 50, and 75 °C, which was set as the reactor temperature, were investigated. Low-temperature oxidation experiments designed at Pusan National University, based on papers related to low-temperature experiments, were conducted to analyze the constant of oxidation reactions. The petrographic characteristics of the coals were analyzed using a coal petrographic microscope spectrophotometer for determining their vitrinite reflectance and morphology, and the coals were extracted after the low-temperature oxidation experiments. After these analyses, vitrinite reflectance changed, and the normalized k, which is the difference between the constant of reaction from 25 °C to (the setting temperatures of) 50 and 75 °C, was also calculated. By comparing the oxidation rates of the coals and the corresponding petrographic analyses, the cause of spontaneous combustion can be deduced and a prediction can be made about which coal burns most efficiently at a low temperature.

Treatment of Large and Massive Rotator Cuff Tears: Does Infraspinatus Muscle Tear Affect Repair Integrity?

BACKGROUND: Clinical outcomes and prognosis of large and massive rotator cuff tears are known to be unpredictable not only in degeneration of the rotator cuff, but also due to a high rate of retear. METHODS: Totally, 81 patients who had undergone arthroscopic rotator cuff repair from May 2008 to February 2016 were evaluated in our study. Clinical and functional evaluations were performed with the Constant score and the University of California, Los Angeles (UCLA) score, as well as full physical examination of the shoulder. All patients were confirmed to have magnetic resonance imaging (MRI) of tendon healing at least 1 year postoperatively. RESULTS: The average age at the time of surgery was 65 years (range, 47-78 years). The average duration of postoperative time in which a follow-up MRI was performed was 36.1 months (range, 12-110 months). Large tears were present in 48 cases (59.3%) and massive tears in 33 cases (40.7%). Overall, there were 33 retear cases (40.7%). All the average clinical outcome scores were significantly improved at the last follow-up (p<0.001), although repair integrity was not maintained. Compared to type A, types C, and D of the Collin's classification showed significantly higher retear rates (p=0.036). CONCLUSIONS: Arthroscopic rotator cuff repair yields improved clinical outcomes and a relatively high degree of patient satisfaction, despite the repair integrity not being maintained. Involvement of the subscapularis muscle or infraspinatus muscle had no effect on the retear rate.

Current Trends for Treating Lateral Epicondylitis.

Lateral epicondylitis, also known as 'tennis elbow', is a degenerative rather than inflammatory tendinopathy, causing chronic recalcitrant pain in elbow joints. Although most patients with lateral epicondylitis resolve spontaneously or with standard conservative management, few refractory lateral epicondylitis are candidates for alternative non-operative and operative modalities. Other than standard conservative treatments including rest, analgesics, non-steroidal anti-inflammatory medications, orthosis and physical therapies, nonoperative treatments encompass interventional therapies include different types of injections, such as corticosteroid, lidocaine, autologous blood, platelet-rich plasma, and botulinum toxin, which are available for both short-term and long-term outcomes in pain resolution and functional improvement. In addition, newly emerging biologic enhancement products such as bone marrow aspirate concentrate and autologous tenocyte injectates are also under clinical use and investigations. Despite all non-operative therapeutic trials, persistent debilitating pain in patients with lateral epicondylitis for more than 6 months are candidates for surgical treatment, which include open, percutaneous, and arthroscopic approaches. This review addresses the current updates on emerging non-operative injection therapies as well as arthroscopic intervention in lateral epicondylitis.

Autologous Bone Marrow Cell Stimulation and Allogenic Chondrocyte Implantation for the Repair of Full-Thickness Articular Cartilage Defects in a Rabbit Model.

OBJECTIVE: The aim of this study was to evaluate the results of autologous bone marrow cell stimulation and allogenic chondrocyte implantation using 3-dimensional gel-type fibrin matrix in an animal model. DESIGN: Eighteen rabbits were divided into 2 treatment groups. One group was treated with a microfracture and covering of it with gel-type fibrin (AutoBMS; n = 9), and the other group was treated with allogenic chondrocytes mixed gel-type fibrin at the cartilage defect (AlloCI; n = 9). The control group was untreated cartilage defect at the other side knee of each object. Twelve weeks after treatment, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system, immunohistochemical staining, and modified O'Driscoll grading system. RESULTS: The ICRS scores were similar in the AutoBMS (9.44 ± 2.44) and the AlloCI (9.33 ± 1.67) groups ( P < 0.05). Immunohistochemical staining confirmed higher expression of cartilaginous collagen for both groups. The average difference (AutoBMS, 31.89 ± 6.54; AlloCI, 32.89 ± 5.25) in the modified O'Driscoll scores appeared to be nonsignificant ( P > 0.05); however, both treatment groups showed significantly higher scores with respect to their control group (18.45 ± 1.65; 18.97 ± 1.58) ( P < 0.05). CONCLUSION: This experimental study suggests autologous bone marrow cells stimulation and implantation of allogenic chondrocytes are both useful methodologies for regenerating hyaline-like cartilage in full-thickness cartilage defects in animal model.

Wiring technique for lesser trochanter fixation in proximal IM nailing of unstable intertrochanteric fractures: A modified candy-package wiring technique.

INTRODUCTION: The purpose of this study was to introduce a new surgical technique, that involves modified Candy-package wiring followed by IM nailing fixation and to determine the clinical and radiological results obtained in patients with unstable intertrochanteric fractures with a lesser trochanter fragment. MATERIALS AND METHODS: This study included 22 patients who were undergone proximal IM nailing with lesser trochanter wiring between January 2014 to June 2015. All patients were treated with minimally invasive technique of candy-package wiring for lesser trochanter fragments. The mean age was 75.8 years (range, 53-88) and average follow-up period was 15.1 months (range, 12-24). Each patient was followed up for a minimum of 12 months and their clinical and radiological results were analyzed. RESULTS: The mean period required for fracture union was 16.6 weeks. (range, 8-25) and union was successfully completed in all cases. The WOMAC scores at the last F/U visit (average; 45.4, range; 21-75) were not significantly different to pre-trauma status (average; 36.5, range; 19-59) (p=0.087). In comparison of ambulatory capacity prior to trauma, ambulatory aggravation was noted in four cases (18.2%), and eighteen cases (81.8%) was sustained walking ability of prior of trauma. Wiring breakage was found in two cases and heterotrophic ossification in one case. There were no functional deficeit related to the radiologic finding in these patients. With regard to postoperative complications, were no cut-outs, breakage, or pullout of screws. CONCLUSION: When surgically repairing unstable intertrochanteric fractures with lesser trochanter comminution using proximal IM nailing method, the modified Candy-packaging wiring technique increases the fixation force at the fracture site. Thus, through this technique, both firm fixation of the lesser trochanter and more stable bony union were obtained.

Factors associated with clinical and structural outcomes after arthroscopic rotator cuff repair with a suture bridge technique in medium, large, and massive tears.

BACKGROUND: This study was conducted to evaluate clinical outcomes, maintenance of repair integrity, and retear rate after arthroscopic rotator cuff repair by a suture bridge technique among patients with medium, large, and massive rotator cuff tears. METHODS: We evaluated 147 patients who had undergone arthroscopic rotator cuff repair. Clinical and functional evaluations were performed with the Constant and University of California-Los Angeles scores. All patients were confirmed to have magnetic resonance imaging evidence of tendon healing at least 12 months postoperatively. RESULTS: The average postoperative time to follow-up magnetic resonance imaging was 23.4 months (range, 12-48 months). A total of 25 (17.0%) retears were observed. All clinical outcome scores were improved significantly at follow-up. Larger intraoperative tear sizes were correlated with higher retear rates. The incidence of retear was also higher in cases in which the preoperative fatty degeneration grade was higher. The incidence of retear increased with age and in the heavy worker group (e.g., farmers, carriers, car mechanics) but was not statistically significant. CONCLUSIONS: Arthroscopic rotator cuff repair by a suture bridge technique yields improvements in clinical outcome measures and a relatively high degree of patient satisfaction despite the fact that repair integrity is not maintained in many cases.

Primary Ewing sarcoma of lumbar spine in an 8-year-old boy: a case report.

Primary Ewing's sarcoma of the mobile spine is rare, but nevertheless, is the second most common primary malignant bone neoplasm in children. Furthermore, in contrast to long bone involvement, delays may occur because symptoms may not be present until neurological deficits occur. Here, we report a case of an 8-year-old boy with lower back pain and radicular pain on the posterior lower extremities with tingling and progressively reduced sensation in both feet. The patient initially seemed to have muscle sprain but was eventually diagnosed with Ewing's sarcoma of the L5 vertebra with intraspinal extension.