Pectolinarigenin regulates the tumor-associated proteins in AGS-xenograft BALB/c nude mice.

BACKGROUND: Pectolinarigenin (PEC) is a flavone extracted from Cirsium, and because it has anti-inflammatory properties, anti-cancer research is also being conducted. The objective of this work was to find out if PEC is involved in tumor control and which pathways it regulates in vivo and in vitro. METHODS: AGS cell lines were xenografted into BALB/c nude mice to create tumors, and PEC was administered intraperitoneally to see if it was involved in tumor control. Once animal testing was completed, tumor proteins were isolated and identified using LC-MS analysis, and gene ontology of the found proteins was performed. RESULTS: Body weight and hematological measurements on the xenograft mice model demonstrated that PEC was not harmful to non-cancerous cells. We found 582 proteins in tumor tissue linked to biological reactions such as carcinogenesis and cell death signaling. PEC regulated 6 out of 582 proteins in vivo and in vitro in the same way. CONCLUSION: Our findings suggested that PEC therapy may inhibit tumor development in gastric cancer (GC), and proteomic research gives fundamental information about proteins that may have great promise as new therapeutic targets in GC.

Clinical Efficacy and Safety of the Intra-articular Injection of Autologous Adipose-Derived Mesenchymal Stem Cells for Knee Osteoarthritis: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Intra-articular injection of autologous culture-expanded adipose-derived mesenchymal stem cells (ADMSCs) has introduced a promising treatment option for knee osteoarthritis. Although the clinical efficacy and safety of ADMSCs have been reported, the treatment remains controversial owing to the small sample sizes and heterogeneous osteoarthritis grades in previous studies. PURPOSE: To assess the efficacy and safety of intra-articular injection of ADMSCs as compared with placebo in alleviating pain and improving functional capacity in a large sample of patients with knee osteoarthritis of Kellgren-Lawrence (K-L) grade 3. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: This phase III multicenter clinical trial was a double-blind randomized controlled study that included 261 patients with K-L grade 3 symptomatic knee osteoarthritis who were administered a single injection of autologous culture-expanded ADMSCs or placebo. Clinical data were assessed at baseline and at 3 and 6 months after the injection. The primary endpoints were improvements in 100-mm visual analog scale (VAS) for pain and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) for function at 6 months after the injection. The secondary endpoints included clinical and radiologic examinations and safety after injection. The changes in cartilage defects after injection were assessed by magnetic resonance imaging at 6 months. RESULTS: The ADMSC and control groups included 125 and 127 patients available for follow-up, respectively. At 6 months, the ADMSC group showed significantly better improvements in 100-mm VAS (ADMSC vs control, 25.2 vs 15.5; P = .004) and total WOMAC score (21.7 vs 14.3; P = .002) as compared with the control group. The linear mixed model analysis indicated significantly better improvements in all clinical outcomes in the ADMSC group after 6 months. At 6 months, the ADMSC group achieved significantly higher proportions of patients above the minimal clinically important difference in 100-mm VAS and WOMAC score. Radiologic outcomes and adverse events did not demonstrate significant differences between the groups. No serious treatment-related adverse events were observed. Magnetic resonance imaging revealed no significant difference in change of cartilage defects between the groups at 6 months. CONCLUSION: Intra-articular injection of autologous culture-expanded ADMSCs provided significant pain relief and functional improvements in patients with K-L grade 3 osteoarthritis. Long-term results are needed to determine the disease-modifying effects of ADMSCs, such as structural changes, and the duration of effect of intra-articular injection of ADMSCs in knee osteoarthritis. REGISTRATION: NCT03990805 (ClinicalTrials.gov identifier).

Cadmium induces cytotoxicity in normal mouse renal MM55.K cells.

The toxicity of cadmium (Cd) occurs through accumulation in the environment. The precise mechanism underlying Cd toxicity remains unclear. Therefore, in the present study, we studied the effects of Cd on MM55.K cells and investigated the mechanisms underlying Cd-induced cell death. CdCl2 significantly elevated apoptotic cell death, mitochondrial membrane potential (ΔΨm) loss, and caspase-dependent cell death. Moreover, immunoblotting results revealed that CdCl2 down-regulated the inhibitor of apoptotic protein such as survivin and Bcl-2 which led to the activation of caspase-3 and the cleavage of PARP in MM55.K cells. Besides, CdCl2 caused the up-regulation of ROS-related proteins such as HO-1 and ER stress-related proteins such as GRP78 and CHOP in MM55.K cells. CdCl2 toxicity resulted in the down-regulation of the AKT pathway that leads to the up-regulation of phosphorylated JNK and p38 in MM55.K cells. Thus, CdCl2 induce toxicity by AKT/MAPK regulation and causing ROS production, ER stress, ΔΨm loss, and apoptotic cell death in normal mouse renal cells.

Tacky-Free Polyurethanes Pressure-Sensitive Adhesives by Molecular-Weight and HDI Trimer Design.

Polyurethane pressure-sensitive adhesives (PU-PSAs) with satisfactory tack, cohesion, and removability were newly developed through the synthetic process by reacting methylene diisocyanate, poly(ethylene glycol) (PEG), and a 1,4-butanediol chain extender based on the different HDI/HDI trimer ratios. The sticking properties of PU-PSAs depended on both the HDI/HDI trimer ratio and crosslinking-agent composition in the formulation. The molecular weight (MW) dependence of adhesion in PU-PSA was observed in the range of 1000 < Mn < 3000, suggesting that the increase in MW limits the pressure-sensitive adhesion of these samples. The differences in the crosslinking-density significantly affected the cohesion, adhesion, and tack in PU-PSA. The formulation of 50 wt.% 600PEG and 50 wt.% crosslinking-agent and an HDI/HDI trimer ratio of 1.0 led to the optimal balance between the adhesion and cohesion properties owing to the sufficient tack, high 180-peel strength, and good cohesion.

Osteonecrosis of the medial tibial plateau after intra-articular corticosteroid injection: A case report.

RATIONALE: Intra-articular corticosteroid injection (IACI) is a cost-effective conservative treatment of mild-to-moderate osteoarthritis. Adverse events after this procedure range from life-threatening systemic reactions to self-limiting local reactions. To our knowledge, this is the 1st report of osteonecrosis (ON) in the medial tibial plateau after IACI. PATIENT CONCERNS: An 81-year-old female visited our hospital due to left knee pain of increasing intensity. She presented the sudden onset of severe acute knee pain with long lasting knee pain for several years. DIAGNOSIS: The diagnosis was confirmed ON of medial tibial plateau of knee joint by pathologic finding. INTERVENTIONS: We conducted a posterior stabilized total-knee arthroplasty with no requirement for bone grafting or additional prosthesis, such as metal augments or stems. OUTCOMES: At the postoperative 1 year follow-up, the patient was satisfied with the surgery and had no pain during walking and active knee motion. LESSONS: This case especially stress the possibility of ON in medial tibia plateau after IACI. Therefore, clinicians should monitor symptoms after IACI to enable early detection of this complication.

An unusual mechanism of coracoid fracture in a beginner golfer.

Golfers may injure themselves as a result of repetitive asymmetrical loads exerted on the body by poor swing mechanics. If the repetitive sub-maximal loading is not removed, this repetitive loading will exceed the adaptive capacity of bone, eventually resulting in a stress fracture. Stress fracture of the scapula due to golfing is extremely rare. Only two cases of acromion fracture have been reported. A rare case of nontraumatic coracoid fracture in a 50-year-old female beginner golfer is reported here. The mechanism of injury is also discussed. Level of evidence Level IV.

Sweet's syndrome: a clinical entity need to discriminate against acute haematogenous periprosthetic joint infection.

Sweet's syndrome (SS) or acute febrile neutrophilic dermatosis is an uncommon condition. It is characterized by fever, polymorphonuclear leukocytosis, painful erythematous cutaneous plaques, and dense dermal infiltrate of neutrophils without vasculitis at the site of skin lesions. Lesions in SS might enlarge and coalesce with increasing dermal oedema, resulting in pseudo-vesicular appearance mimicking joint infections. Here, a rare case of SS mimicking acute haematogenous periprosthetic infection in a 74-year-old woman with a history of total knee arthroplasty is reported. This report aims to elaborate clinical various manifestations of SS in a patient with a history of total knee arthroplasty. In addition, this report describes how to discriminate inflammation between SS and periprosthetic joint infection. Level of evidence V.

Arthroscopic management of lesser tuberosity osteochondroma causing impingement and subscapularis tear of the shoulder.

Although the proximal humerus is a common site of osteochondroma, osteochondroma arising from the lesser tuberosity of the proximal humerus is rare. Because of the anatomy of the shoulder, mechanical impingement can occur via direct contact of the protruding lesser tuberosity against the glenoid rim or coracoid. In younger patients, this may cause isolated tearing of the subscapularis. In this study, is presented a rare case of osteochondroma on the lesser tuberosity that caused a subscapularis tear after shoulder impingement in a 34-year-old male. This case was managed using an arthroscopic approach. One year after the surgery, the patient had recovered a normal range of motion, with the resolution of impingement symptoms and the tearing of the subscapularis. Level of evidence IV.

Clavicle fracture after reverse total shoulder arthroplasty: a case report with literature review.

In reverse total shoulder arthroplasty, retensioning of the deltoid muscle is essential for regaining active elevation. However, the procedure remains problematic, in that it may potentially produce complications not only because it is a complex procedure but also because it causes anatomical changes. We experienced a rare case of a 64-year-old woman presenting with non-traumatic clavicle fracture after reverse total shoulder arthroplasty via a deltopectoral approach. In our case, the patient presented with pain in the clavicle area, which worsened during joint movement. Therefore, surgeons should consider the possibility of clavicle fracture in patients presenting with pain in the clavicle area which worsens.

Comparison of retrograde nailing and minimally invasive plating for treatment of periprosthetic supracondylar femur fractures (OTA 33-A) above total knee arthroplasty.

INTRODUCTION: Retrograde intramedullary (IM) nailing and minimally invasive plate osteosynthesis (MIPO) using locking plate are typically considered the gold standards of treatment for periprosthetic supracondylar femoral fractures above total knee arthroplasty (TKA). METHODS: Forty-one consecutive patients treated with either retrograde nailing (nail group, n = 20) or minimally invasive plating (plate group, n = 21) for periprosthetic supracondylar femoral fractures between March 2003 and January 2014 were retrospectively reviewed. Clinical functions [arc range of motion and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score] and bony outcomes (bony union and malunion) were evaluated. RESULTS: There was no statistical difference between the nail and plate groups in age (p = 0.665), one-year postoperative arc range of motion (p = 0.642), preoperative WOMAC score (p = 0.076), postoperative one-year WOMAC score (p = 0.135), and union time (p = 0.081). The mean union time of the nail group and the plate group was 4.3 months (range 3-12 months) and 3.6 months (range 3-5 months), respectively. There were three cases of malalignment in the nail group, whereas there was one case of malalignment in the plate group (p = 0.343). One case of nailing using a short nail demonstrated nail breakage. CONCLUSIONS: Although retrograde nailing was found to have a slightly higher rate of malunion compared to minimally invasive plating, there was no statistically significant difference between both treatment options in terms of clinical outcomes. Regardless of which implant is used, the proper application is essential in management of periprosthetic supracondylar femoral fractures above TKA.

Risk of Anterior Femoral Notching in Navigated Total Knee Arthroplasty.

BACKGROUND: We retrospectively investigated the prevalence of femoral anterior notching and risk factors after total knee arthroplasty (TKA) using an image-free navigation system. METHODS: We retrospectively reviewed 148 consecutive TKAs in 130 patients beginning in July 2005. Seventy knees (62 patients) underwent conventional TKA, and 78 knees (68 patients) received navigated TKA. We investigated the prevalence of femoral anterior notching and measured notching depth by conventional and navigated TKA. Additionally, the navigated TKA group was categorized into two subgroups according to whether anterior femoral notching had occurred. The degree of preoperative varus deformity, femoral bowing, and mediolateral suitability of the size of the femoral component were determined by reviewing preoperative and postoperative radiographs. The resection angle on the sagittal plane and the angle of external rotation that was set by the navigation system were checked when resecting the distal femur. Clinical outcomes were compared using range of motion (ROM) and the Hospital for Special Surgery (HSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAX) scores between the two groups. RESULTS: The prevalence of anterior femoral notching by conventional TKA was 5.7%, and that for navigated TKA was 16.7% (p = 0.037). Mean notching depth by conventional TKA was 2.92 ± 1.18 mm (range, 1.8 to 4.5 mm) and 3.32 ± 1.54 mm (range, 1.55 to 6.93 mm) by navigated TKA. Preoperative anterior femoral bowing was observed in 61.5% (p = 0.047) and both anterior and lateral femoral bowing in five cases in notching group during navigated TKA (p = 0.021). Oversized femoral components were inserted in 53.8% of cases (p = 0.035). No differences in clinical outcomes for ROM or the HSS and WOMAX scores were observed between the groups. A periprosthetic fracture, which was considered a notching-related side effect, occurred in one case each in the conventional and navigated TKA groups. CONCLUSIONS: Surgeons should be aware of the risks associated with anterior femoral notching when using a navigation system for TKA. A modification of the femoral cut should be considered when remarkable femoral bowing is observed.

A tenosynovial giant cell tumor arising from femoral attachment of the anterior cruciate ligament.

The localized type of tenosynovial giant cell tumor usually occurs on the palmar side of fingers and toes. Tenosynovial giant cell tumors of the tendon sheath are rarely intra-articular. We report a giant cell tumor of the tendon sheath arising from femoral attachment of the anterior cruciate ligament and its treatment with arthroscopy in a 28-year-old man.

New morphological features for grading pancreatic ductal adenocarcinomas.

Pathological diagnosis is influenced by subjective factors such as the individual experience and knowledge of doctors. Therefore, it may be interpreted in different ways for the same symptoms. The appearance of digital pathology has created good foundation for objective diagnoses based on quantitative feature analysis. Recently, numerous studies are being done to develop automated diagnosis based on the digital pathology. But there are as of yet no general automated methods for pathological diagnosis due to its specific nature. Therefore, specific methods according to a type of disease and a lesion could be designed. This study proposes quantitative features that are designed to diagnose pancreatic ductal adenocarcinomas. In the diagnosis of pancreatic ductal adenocarcinomas, the region of interest is a duct that consists of lumen and epithelium. Therefore, we first segment the lumen and epithelial nuclei from a tissue image. Then, we extract the specific features to diagnose the pancreatic ductal adenocarcinoma from the segmented objects. The experiment evaluated the classification performance of the SVM learned by the proposed features. The results showed an accuracy of 94.38% in the experiment distinguishing between pancreatic ductal adenocarcinomas and normal tissue and a classification accuracy of 77.03% distinguishing between the stages of pancreatic ductal adenocarcinomas.

Automatic differential diagnosis of pancreatic serous and mucinous cystadenomas based on morphological features.

Generally, pathological diagnosis using an electron microscope is time-consuming and likely to result in a subjective judgment, because pathologists perform manual screening of tissue slides at high magnifications. Recently, the advent of digital pathology technology has provided the basis for convenient screening and quantitative analysis by digitizing tissue slides through a computer system. However, a screening process with high magnification still takes quite a long time. To solve these problems, recently the use of computer-aided design techniques for performing pathologic diagnosis has been increasing in digital pathology. For pathological diagnosis, we need different diagnostic methods for different regions with different characteristics. Therefore, in order to effectively diagnose different lesions and types of diseases, a quantitative method for extracting specific features is required in computerized pathologic diagnosis. This study is about an automated differential diagnosis system to differentiate between benign serous cystadenoma and possibly-malignant mucinous cystadenoma. In order to diagnose cystic tumors, the first step is identifying a cystic region and inspecting its epithelial cells. First, we identify the lumen boundary of a cyst using the Direction Cumulative Map considering 8-ways. Then, the Epithelial Nuclei Identification algorithm is used to discern epithelial nuclei. After that, three morphological features for the differential diagnosis of mucinous and serous cystadenomas are extracted. To demonstrate the superiority of the proposed features, the experiments compared performance of the classifiers learned by using the proposed morphological features and the classical morphological features based on nuclei. The classifiers in the simulations are as follows; Bayesian Classifier, k-Nearest Neighbors, Support Vector Machine, and Artificial Neural Network. The results show that all classifiers using the proposed features have the best classification performance.

Arthroscopic treatment for osteoarthritic knee.

Arthroscopic treatment for osteoarthritis of the knee has been widely performed as one of the surgical options, in spite of persisting concerns regarding its efficacy. Arthroscopic debridement is a general term that is used to cover many procedures, including lavage, partial meniscectomy, removal of loose body, synovectomy, chondroplasty, removal of offending osteophytes, and/or microfracture. Recently, the role of arthroscopy in managing the osteoarthritic knee has been challenged by elusive consensus on its usefulness. Therefore, we review the available literatures for the arthroscopic intervention in knee osteoarthritis and summarized evidences for proper patient selection, which is a paramount factor to achieve the surgical goal of the arthroscopic treatment in osteoarthritic knee.

Sulfuretin, a major flavonoid isolated from Rhus verniciflua, ameliorates experimental arthritis in mice.

AIM: Sulfuretin, a major flavonoid isolated from Rhus verniciflua, is known to have anti-inflammatory effects. However, the mechanisms underlying the anti-inflammatory effect of sulfuretin on rheumatoid arthritis have not been elucidated. In this study we investigated whether sulfuretin treatment modulates the severity of arthritis in an experimental model. MAIN METHODS: We evaluated the effects of sulfuretin on tumor necrosis factor-α (TNF-α)-treated human rheumatoid fibroblast-like synoviocytes (FLS) in vitro and on collagen-induced arthritis (CIA) mice in vivo. KEY FINDINGS: In vitro experiments demonstrated that sulfuretin suppressed the chemokine production, matrix metalloproteinase secretion, and cell proliferation induced by tumor necrosis factor-α in rheumatoid FLS. In addition, sulfuretin inhibited the osteoclast differentiation induced by macrophage colony-stimulating factor and receptor activator of NF-κB ligand in bone marrow macrophages. In mice with CIA, early intervention with sulfuretin prevented joint destruction, as evidenced by a lower cumulative disease incidence and an absence of diverse disease features based on hind paw thickness, radiologic and histopathologic findings, and inflammatory cytokine levels. In mice with established arthritis, sulfuretin treatment significantly reduced synovial inflammation and joint destruction. The in vitro and in vivo protective effects of sulfuretin were mediated by inhibition of the NF-κB signaling pathway. SIGNIFICANCE: These results suggest that using sulfuretin to block the NF-κB pathway in rheumatoid joints reduces both inflammatory responses and joint destruction. Therefore, sulfuretin may have therapeutic value in preventing or delaying the progression of rheumatoid arthritis.

Unicondylar osteoarticular allograft reconstruction of the distal femur in a patient with a traumatic osteoaticular defect of the lateral femoral condyle.

PURPOSE: The objective of this study was to report the clinical results for a patient with a post-traumatic osteoarticular defect of the lateral femoral condyle treated with unicondylar osteoarticular allograft reconstruction. METHOD: We describe the case with a massive osteoarticular loss of the lateral femoral condyle combined with a grade IIIA open distal femoral diaphyesal fracture. The patient underwent unicondylar osteoarticular reconstruction with an allogenic fresh-frozen condyle. RESULTS: There were no complications after the reconstructive procedure. At the five year follow-up, the patient showed a favorable clinical outcome with a full range of motion of the knee joint. Degenerative changes were seen in the graft compartment, but they did not cause serious functional limitations. CONCLUSION: Unicondylar allograft reconstruction appears to be a surgical option for patients who suffer from a post-traumatic distal femoral osteoarticular defect in which only one condyle is absent or severely damaged.

The Pattern of Use of Oral NSAIDs with or without Co-prescription of Gastroprotective Agent for Arthritic Knee by Korean Practitioners.

PURPOSE: The aim of this study was to describe the patterns of use of non-steroidal anti-inflammatory drugs (NSAIDs) for arthritic knees in clinical practice, particularly focusing on the co-prescription of gastroprotective agents for patients with risk factors for adverse gastrointestinal (GI) events. MATERIALS AND METHODS: Each cross-sectional cohort was a group of outpatients visiting 111 physicians who had prescribed NSAIDs for the patients' arthritic knees for more than three consecutive months. A self-administered questionnaire was completed by each patient and physician. RESULTS: Nine hundred and forty five patients (48%) of the whole 1,960 patients belonged to the group with a high or very high risk for NSAID-induced gastropathy determined by northern California Health Maintenance Organization guidelines. Overall, only less than half of the patients were given co-prescription of gastroprotective agents, regardless of the presence or absence of GI symptoms and irrespective of the level of risk for NSAID-induced gastropathy. CONCLUSIONS: The physician prescribing NSAIDs for arthritic knees should monitor any GI symptoms and the patient monitor anylevel for NSAIDinduced gastropathy, and be willing to add gastroprotective agents as necessary in order to prevent serious adverse GI events.

A distal fluted, proximal modular femoral prosthesis in revision hip arthroplasty.

Most reports on the use of modular femoral stems during revision surgery have involved short follow-up periods. The authors evaluated the clinical and radiographic performance of 59 patients fitted with a distal fix modular stem. The average follow-up period was 8.2 years. Average Harris hip score was improved from 47 to 87.6. Of 19 patients with trochanteric osteotomy, 4 had a displaced greater trochanter. Re-revision was performed in 5 patients, and 3 of these were for subsidence (of these 3, subsidence was associated with dissociation of the coupling part in 1 and with osteotomy nonunion in other 2 [proximal component only]). Modular distally fixed femoral stems were found to offer intraoperative flexibility, but to suffer from subsidence and intraoperative greater trochanter and metaphyseal femoral fractures.

Surgical treatment of thoracic outlet syndrome secondary to clavicular malunion.

According to the literature, thoracic outlet syndrome (TOS) secondary to the malunion of displaced fractures of the clavicle is rare. Various surgical methods, including simple neurolysis, resection of the first rib or clavicle and corrective osteotomy, have been reported. We report a case of TOS secondary to malunion of the clavicle that was treated by an anterior and middle scalenectomy without a rib resection.