Association of the DNMT3B -579G>T polymorphism with risk of thymomas in patients with myasthenia gravis

Increasing evidence suggests a contribution of epigenetic processes in promoting cancer and autoimmunity. Myasthenia gravis (MG) is an autoimmune disease mediated, in approximately 80% of the patients, by antibodies against the nicotinic acetylcholine receptor (AChR+). Moreover, epithelial tumours (thymomas) are present in about 10-20% of the patients, and there is indication that changes in DNA methylation might contribute to the risk and progression of thymomas. However, the role of epigenetics in MG is still not completely clarified. In the present study we investigated if a common polymorphism (-579G>T: rs1569686) in the promoter of the DNMT3B gene coding for the DNA methyltransferase 3B, an enzyme that mediates DNA methylation, increases the risk to develop MG or MG-associated thymomas. The study polymorphism was selected based on recent reports and a literature meta-analysis suggesting association with increased risk of various types of cancer. We screened 324 AChR+ MG patients (140 males and 184 females, mean age 56.0 \ub1 16.5 years) and 735 healthy matched controls (294 males and 441 females, mean age 57.3 \ub1 15.6 years). 94 of the total MG patients had a thymoma. While there was no association with the whole cohort of MG patients, we found a statistically significant association of the DNMT3B-579T allele (OR = 1.51; 95% CI=1.1-2.1, P = 0.01) and the TT homozygous genotype (OR = 2.59; 95% CI=1.4-4.9, P = 0.006) with the risk of thymoma. No association was observed in MG patients without thymoma, even after stratification into clinical subtypes. Present results suggest that the DNMT3B-579T allele might contribute to the risk of developing thymoma in MG patients, particularly in homozygous TT subjects

Categories and Word Meanings Are Not Single Entities in the Mind

But the idea that categories and word meanings are single mental entities can also have a distributed connectionist interpretation. In distributed connectionist models an entity is not represented by a single network unit as in localist connectionist models. However, categories or word meanings can be considered as corresponding to some particular pattern of activation on an ensemble of network units and therefore still interpreted as single entities. Categories and word meanings tend to be interpreted as single entities that are activated in the mind when an individual categorizes the world or uses language. We argue that this view is mistaken. Connectionist simulations of populations of neural networks that live and reproduce in an environment show that categories and word meanings are open and changing collections of activation patterns in the network's internal units rather than single activation patterns. We think that viewing categories and word meanings as single entities in t..

Tibial inlay for posterior cruciate ligament reconstruction. A systematic review

Although no consensus has been reached regarding the management of PCL deficiency, in vitro and in vivo studies have investigated whether the tibial inlay technique restores the anatomical site of insertion of the PCL, prevents elongation, stretching, graft failure, and improves long-term PCL stability. A systematic search using PubMed, Ovid, the Cochrane Reviews, and Google Scholar databases using 'posterior cruciate ligament tear', 'Tibial inlay technique' and 'posterior cruciate ligament reconstruction' as keywords identified 71 publications, of which 10 were relevant to the topic, and included a total of 255 patients. The tibial inlay technique restores the anatomic insertion site of the PCL, eliminates the killer turn effect, and places the graft at lower potential risk for abrasion and subsequent rupture. It has the disadvantages of increased operating time and risk to the posterior neurovascular structures. There was no evidence of an association between outcome results and Coleman methodology score, but the Coleman methodology scores correlated positively with the level-of-evidence rating. The methodological quality of the studies included has not improved over the years. Given the few reported published findings, we cannot ascertain whether this procedure may provide a consistent alternative to commonly used PCL surgical strategies. The lack of published randomized clinical trials and few reported findings did not allow to ascertain whether the tibial inlay for posterior cruciate ligament reconstruction may provide a consistent alternative to commonly used PCL surgical strategies and to demonstrate procedure efficacy. © 2010 Elsevier B.V

Understanding and preventing complications in repairing rotator cuff tears

Repair of rotator cuff tears is a common procedure. Prior to approaching this surgery, it should be realized that each surgical step can lead to complications, including those related to positioning and anaesthesia. Stiffness, infection and failure of repair are the more frequent complications reported. Copyright © 2012 S. Karger AG, Basel

Meniscectomy as a risk factor for knee osteoarthritis: A systematic review

Introduction: This review defines the recognized risk factors responsible for the development of knee osteoarthritis after surgical management of meniscal tears. Sources of data: We performed a literature search using Medline, Ovid, Cochrane and Google Scholar using the keywords: 'Meniscal tears', 'meniscectomy', 'osteoarthritis', 'complications' and 'risk factors'. Thirty-two published studies were identified. Areas of agreement: In the long term, osteoarthritis develops in the knee of patients undergoing surgery for meniscal tears. The Coleman methodology score showed great heterogeneity in terms of patient characteristics and outcome assessment. Amount of meniscus removed, duration of pre-operative symptoms and lateral meniscectomy show strong statistical association to onset of knee osteoarthritis. Areas of controversy: We did not find univocal findings defining the risk factors responsible for the development of post-operative knee osteoarthritis. Growing points: There is a need for standardized clinical and imaging validated scale to improve definition of post-operative knee osteoarthritis to allow easier and more reliable comparison of outcomes in different studies. Areas timely for developing research: Appropriately powered randomized controlled trials reporting clinical and imaging-related outcomes in patients undergoing arthroscopic minimally invasive procedures and meniscal suturing should be performed. Comparing imaging findings of patients undergoing arthroscopic partial and open meniscectomy, a lower incidence of knee osteoarthritic evolution was detected after arthroscopy. The amount of removed meniscus is the most important predictor factor for the development of osteoarthritis. Minimally invasive procedures seem to reduce the incidence of long-term osteoarthritic changes of the knee compared with more invasive open and or arthroscopic procedures. © The Author 2010. Published by Oxford University Press. All rights reserved

Glenohumeral arthropathy following stabilization for recurrent instability

Little attention has been focused on the most common risk factors for post-operative glenohumeral arthropathy in patients undergoing open and arthroscopic stabilization. We performed a literature search using Medline, Cochrane and Google Scholar using the keywords: 'Shoulder instability surgery' in combination with 'glenohumeral osteoarthrosis', 'recurrent shoulder dislocation' in combination with 'surgery' and 'complications'. We identified 33 published studies. There is evidence of long-term postoperative glenohumeral arthropathy in patients undergoing surgical management for shoulder instability. The Coleman methodology score showed great heterogeneity in terms of study design, patient characteristics, management methods and outcome assessment and generally low methodological quality. Follow-up length, age at first dislocation episode and limited external rotation have been shown to be strongly associated with shoulder arthropathy. There is no univocal outcome assessment available. To define the risk factors responsible for development of postoperative glenohumeral arthropathy, controversial findings have been detected. A common validated scale for clinical and imaging measurements for shoulder arthropathy is needed, so as to allow easier and more reliable comparison of outcomes in different studies. Patients should receive controlled imaging assessment (MR and radiographs) in addition to clinical examination. There is a need to perform appropriately powered randomized clinical trials comparing clinical and imaging related outcomes in patients undergoing open, arthroscopic and conservative management for shoulder instability. Standard diagnostic assessment, common and validated clinical and imaging scoring systems are needed. © 2010 The Author

Management of combined ACL-MCL tears: A systematic review

Introduction: The optimal management for combined anterior cruciate ligament-medial collateral ligament (ACL-MCL) injuries is controversial. Sources of data: We performed a literature search using Medline, Cochrane and Google Scholar using the keywords: 'ACL' and 'MCL' in combination with 'surgery treatment', 'conservative treatment', 'surgery management', 'conservative management', 'surgical treatment' and 'surgical management'. We identified 23 published studies. Areas of agreement: Conservative and surgical management for combined ACL-MCL injuries resulted in different functional outcomes. The Coleman Methodology Score showed great heterogeneity in terms of study design, patient characteristics, management methods and outcome assessment and generally low methodological quality. Areas of controversy: Given the heterogeneity in terms of treatment and results, we did not find a univocal trend over the years regarding MCL management (conservative or surgical). The use of several scoring systems did not allow us to compare outcomes in the different studies. Growing points: There is a need for a common validated scale for clinical measurements for ACL-MCL injuries, so as to allow easier and more reliable comparison of outcomes in different studies. To improve diagnostic certainty of combined ACL-MCL injuries, all patients should have imaging assessment (MR and stress-radiography) in addition to clinical examination. Areas timely for developing research: There is a need to perform appropriately powered randomized clinical trials of conservative and surgical treatment of combined ACL-MCL injuries, using standard diagnostic assessment, common and validated scoring system comparing reported outcomes and duration of follow-up more than 2 years. © The Author 2009. Published by Oxford University Press. All rights reserved

Comparison of arthroscopic rotator cuff repair in healthy patients over and under 65 years of age

We compared the outcomes of arthroscopically repaired rotator cuff tears in 28 patients older than 65 years (the over 65 group: median age 70 years) with a control group of 28 patients younger than 65 years (the under 65 group: median age 57 years). The groups were similar in regard to sex distribution, surgical technique, and post-operative rehabilitation programmes, but different in age. After careful arthroscopic evaluation of the full-thickness rotator cuff tear, rotator cuff repair and biceps tenotomy were performed in all patients. Pre- and post-operatively, each patient was evaluated for range of motion, shoulder score (UCLA), and SF-36 self-administered questionnaire. Comparing pre- versus post-operative status at a minimum 24 months follow-up, forward elevation, internal and external rotation, modified UCLA rating system scores, and SF-36 scores improved significantly in both groups, with no significant difference between the groups. At the last follow-up, strength improved significantly in both groups, with non-significant intergroup difference. The Popeye sign was detected in 13/28 (46%) of the patients in the over 65 group and in 11/28 (39%) in the under 65 group (Ï\u87 = 0.29) with non-significant difference between the two groups. In selected active patients older than 65, arthroscopic rotator cuff repair associated with biceps tenotomy (when necessary) can yield clinical and related quality of life outcomes similar to those of patients younger than 65 years. © 2010 Springer-Verlag

Recurrence of synovial chondromatosis of the Hoffa's body

Synovial chondromatosis of Hoffa's body is uncommon. Recurrences usually result from incomplete removal of the loose bodies or diseased synovium at the initial surgery. We report a patient with synovial chondromatosis localized into the Hoffa's body who presented with anterior knee pain and mechanical symptoms. At the first arthroscopy, all pathological tissue was removed. At 1-year follow-up, clinical and radiographic examinations were normal. Symptoms recurred at 3 years, when a bony mass in the Hoffa's body was evident on MRI. The mass was removed through a mini-arthrotomy. Histology excluded malignancy. At 10-year follow-up, the patient remained free of symptoms. Synovial chondromatosis can occur with unusual patterns of recurrence. The growth of a large size mass confined to fat pad without intra-articular involvement does not allow to exclude the diagnosis of recurrent synovial chondromatosis. © Springer-Verlag 2009

Creatinine and nonprotein nitrogen plasma levels: possible etiopathogenetic factors in rotator cuff tears

To determine the plasma levels of nonprotein nitrogen (NPN) and creatinine in healthy patients with rotator cuff tears. The study included 400 subjects. The study group included 200 patients (93 men and 107 women; mean age, 56.8 years; range, 23-81 years) who underwent arthroscopic repair of a rotator cuff tear from 2004 to 2007. The control group included 200 patients (93 men and 107 women; mean age, 53.9 years; range, 20-81 years) who underwent arthroscopy for management of a meniscal tear, with or without articular cartilage damage, in the same period. The 2 groups were frequency-matched by age and sex. Measurement of plasma levels of NPN and creatinine were performed in all patients. Patients with rotator cuff tears showed higher plasma NPN levels within the normal range (P = 0.035) than patients with knee disorders (control group). Creatinine levels were comparable (P = 0.66) in both groups. There appears to be an association between plasma NPN levels and rotator cuff tears. On the basis of our findings, plasma NPN could be involved in the pathogenesis of rotator cuff tears, although we advocate further research to draw more definitive conclusions