Closed rupture of the tibialis anterior tendon : a report of 2 cases

Closed rupture of the tibialis anterior tendon is a rare injury, and it usually affects individuals older than 50 years of age. This rare injury tends to occur spontaneously, and this often delays diagnosis and adequate treatment. Although direct surgical repair of the ruptured tibialis anterior tendon is generally considered the treatment of choice, nonanatomic repair, tendon lengthening, or tendon transfer might be necessary in cases where shortening of the muscle-tendon unit has taken place. In this report, we describe 2 cases that involved the surgical repair of closed ruptures of the tibialis anterior tendon. In the first case, direct repair was undertaken at approximately 6 months after the onset of symptoms, and in the second case repair of the tibialis anterior tendon required augmentation tenodesis with the extensor retinaculum. Level of Clinical Evidence: 4.

A new clinical test in diagnosing quadriceps tendon rupture.

INTRODUCTION: Extensor mechanism ruptures might be easily overlooked and misdiagnosed, and delayed diagnosis of quadriceps tendon rupture is frequent. However, the literature recommends early surgical repair within 72 h. PATIENTS AND METHODS: This paper describes a new simple clinical diagnostic test that directly evaluates the integrity of the distal 5 cm of the quadriceps tendon itself. It consists of inserting a needle in the tendon, proximal to the suspected rupture and mobilising the knee joint. RESULTS: The suspected ruptured quadriceps tendons with a positive 'needle' diagnostic test were confirmed intra-operatively. CONCLUSIONS: This minimally invasive and easily available technique should be considered in the diagnostic work-up and treatment planning of patients with suspected tears of the quadriceps tendon.

Critical evaluation of outcome scales to assess outcome after lateral ankle ligament repair

Introduction: Several scores are commonly used to evaluate patients' postoperative satisfaction after lateral ankle ligament repair, including: AOFAS, FAAM, CAIT and CAIS. Comparing published studies in the literature is difficult, as the same patient can have markedly different results depending on which scoring system is used. The current study aims to address this gap in the literature by developing a system to compare these tests, to allow better analysis and comparison of published studies. Patients and methods: This is a retrospective cohort study of 47 patients following lateral ankle ligament repair using a modified Broström-Gould technique. All patients were operated between 2005 and 2010 by a single surgeon and followed the same post operative rehabilitation protocol. Six patients were excluded from the study because of concomitant surgery. Patients were assessed by an independent observer. We used the Pearson correlation coefficient to analyse the concordance of the scores, as well as scatter plots to assess the linear relationship between them. Results: A linear distribution between the scores was found when the results were analysed using scatter plots. We were thus able to use the Pearson correlation coefficient to evaluate the relationship between each of the different postoperative scores. The correlation was found to be above 0.5 in all cases except for the comparison between the CAIT and the FAAM for the activities of daily living (0.39). We were, therefore, able to compare the results obtained and assess the relative concordance of the scoring systems. The results showed that the more specific the scale is, the worst the score is and inversely. So the CAIT and the CAIS appeared to be more severe than the AOFAS and the FAAM measuring the activities of daily living. The sports subscale of the FAAM demonstrated intermediate results. Conclusion: This study outlines a system to compare different postoperative scores commonly used to evaluate outcome after ankle stabilization surgery. The impact of this study is that it makes comparison of published studies easier, even though they use a variety of different clinical scores, thus facilitating better outcome analysis of operative techniques.

A glycine-arginine domain in control of the human MRE11 DNA repair protein.

Human MRE11 is a key enzyme in DNA double-strand break repair and genome stability. Human MRE11 bears a glycine-arginine-rich (GAR) motif that is conserved among multicellular eukaryotic species. We investigated how this motif influences MRE11 function. Human MRE11 alone or a complex of MRE11, RAD50, and NBS1 (MRN) was methylated in insect cells, suggesting that this modification is conserved during evolution. We demonstrate that PRMT1 interacts with MRE11 but not with the MRN complex, suggesting that MRE11 arginine methylation occurs prior to the binding of NBS1 and RAD50. Moreover, the first six methylated arginines are essential for the regulation of MRE11 DNA binding and nuclease activity. The inhibition of arginine methylation leads to a reduction in MRE11 and RAD51 focus formation on a unique double-strand break in vivo. Furthermore, the MRE11-methylated GAR domain is sufficient for its targeting to DNA damage foci and colocalization with gamma-H2AX. These studies highlight an important role for the GAR domain in regulating MRE11 function at the biochemical and cellular levels during DNA double-strand break repair.

Extracellular matrix components in peripheral nerve repair: how to affect neural cellular response and nerve regeneration?

Peripheral nerve injury is a serious problem affecting significantly patients' life. Autografts are the "gold standard" used to repair the injury gap, however, only 50% of patients fully recover from the trauma. Artificial conduits are a valid alternative to repairing peripheral nerve. They aim at confining the nerve environment throughout the regeneration process, and providing guidance to axon outgrowth. Biocompatible materials have been carefully designed to reduce inflammation and scar tissue formation, but modifications of the inner lumen are still required in order to optimise the scaffolds. Biomicking the native neural tissue with extracellular matrix fillers or coatings showed great promises in repairing longer gaps and extending cell survival. In addition, extracellular matrix molecules provide a platform to further bind growth factors that can be released in the system over time. Alternatively, conduit fillers can be used for cell transplantation at the injury site, reducing the lag time required for endogenous Schwann cells to proliferate and take part in the regeneration process. This review provides an overview on the importance of extracellular matrix molecules in peripheral nerve repair.

Genetic- or transforming growth factor-beta 1-induced changes in epidermal peroxisome proliferator-activated receptor beta/delta expression dictate wound repair kinetics.

Advances in wound care are of great importance in clinical injury management. In this respect, the nuclear receptor peroxisome proliferator-activated receptor (PPAR)beta/delta occupies a unique position at the intersection of diverse inflammatory or anti-inflammatory signals that influence wound repair. This study shows how changes in PPARbeta/delta expression have a profound effect on wound healing. Using two different in vivo models based on topical application of recombinant transforming growth factor (TGF)-beta1 and ablation of the Smad3 gene, we show that prolonged expression and activity of PPARbeta/delta accelerate wound closure. The results reveal a dual role of TGF-beta1 as a chemoattractant of inflammatory cells and repressor of inflammation-induced PPARbeta/delta expression. Also, they provide insight into the so far reported paradoxical effects of the application of exogenous TGF-beta1 at wound sites.

Endovascular thoracic aortic aneurysm repair without angiography.

OBJECTIVE: : Intravascular ultrasound (IVUS) generates high definition circumferential cross-sectional images and provides real-time readout of vascular dimensions, including visualization of vessel branches. We have used it as an alternative to angiography in the endovascular thoracic aneurysm repair work-up. METHODS: : Out of consecutive 203 patients with descending thoracic aortic aneurysm, 89 (43.8%) received endovascular treatment [mean age, 68 ± 8 years; range, 29-82; male, 79 (88.7%); female, 10 (11.3%)] without using angiography during the endovascular procedure. IVUS (6 F, 12.5 MHz probe or 10 F 9 MHz) coupled with fluoroscopy for the placement of radiopaque markers was used for target site identification, landing zone measurement, device positioning, and assessment of endovascular repair. RESULTS: : Hospital mortality was 4/89 (4.5%). Number of devices implanted in each patient was 1.2 (range, 1-3). X-ray exposure time was 12 ± 8 minutes. Median procedure time was 63 ± 20 minutes. Conversion to open surgery was necessary in one patient (1.1%) because of aortic dissection. In nine patients (10.1%) left subclavian artery was covered because of a short neck. Two patients (2.2%) had vascular access lesions and required surgical repair. One patient developed paraplegia (1.1%). Early endoleak was observed in eight patients (8.9%) and 4 (4.5%) required additional procedures (proximal or distal extensions). Late conversion was necessary in one patient (1.1%). CONCLUSIONS: : IVUS provides all information necessary for device selection, target site identification as well as safe and correct deployment of thoracic endoprostheses and makes periprocedural angiography unnecessary, thus avoiding the risk of renal failure because of contrast medium.

Macrophages from Crohn's disease patients exhibit deficient pro-repair functions

BACKGROUND: We previously reported that myeloid cells can induce mucosal healing in a mouse model of acute colitis. Promotion of mucosal repair is becoming a major goal in the treatment of Crohn's disease. Our aim in this study is to investigate the pro-repair function of myeloid cells in healthy donor (HD) and Crohn's disease patients (CD). METHODS: Peripheral blood mononuclear cells (PBMC) from HD and CD patients were isolated from blood samples by Ficoll density gradient. Monocytic CD14+ cells were positively selected by Macs procedure and then differentiated ex-vivo into macrophages (Mφ). The repair function of PBMC, CD14+ monocytic cells and macrophages were evaluated in an in vitro wound healing assay. RESULTS: PBMC and CD14+ myeloid cells from HD and CD were not able to repair at any tested cell concentration. Remarkably, HD Mφ were able to induce wound healing only at high concentration (105 added Mφ), but, if activated with heat killed bacteria, they were able to repair even at very low concentration. On the contrary, not activated CD Mφ were not able to promote healing at any rate, but this function was restored upon activation. CONCLUSION: We showed that CD Mφ in their steady state, unlike HD Mφ, are defective in promoting wound healing. Our results are in keeping with the current theory of CD as an innate immunodeficiency. Defective Mφ may be responsible to the mucosal repair defects in CD patients and to the subsequent chronic activation of the adaptive immune response.

Long term outcome after mitral valve repair : a risk factor analysis

Objectif: La réparation de la valve mitrale constitue le traitement de choix pour restaurer ta fonction de celle-ci. Elle est actuellement reconnue pour garantir une bonne évolution à long terme. Dans le but de faciliter les décisions périopératoires, nous avons analysé nos patients afin de déterminer les facteurs de risque ayant affecté leur évolution. Méthodes: Nous avons étudié rétrospectivement 175 premiers patients consécutifs (âge moyen : 64 +/-10.4 ans ;113 hommes) qui ont subi une réparation primaire de la valve mitrale associée à toute autre intervention cardiaque entre 1986 et 1998. Les facteurs de risque influençant le taux de réopération et la survie à long terme ont été analysés de manière uni et multivariée. Résultats: La mortalité opératoire était de 3.4 % (6 décès, 0 -22 et jours post-opératoires). La mortalité tardive était de 9.1 % (16 décès, 3e-125e mois post-opératoires). Cinq patients ont dû être réopérés. L'analyse actuarielle selon Kaplan-Meier a montré une survie à 1 année de 96 +l-1 %, une survie à 5 ans de 88 +/- 3 % et une survie à 10 ans de 69 +/- 8 %. Après 1 année, la fraction de population sans réopération était de 99 %, elle était de 97 +/-2 % après 5 ans et de 88+/-6 % après 10 ans. L'analyse multivariée a montré qu' un stade NYHA III et IV résiduel ( p=0.001, RR 4.55, 95 % IC :1.85 -14.29), une mauvaise fraction d'éjection préopératoire(p=0.013, RR 1.09, 95 % IC 1.02 -1.18), ,une régurgitation mitrale d'origine fonctionnelle (p=0.018, RR 4.17, 95% IC 1.32-16.67) ainsi qu'une étiologie ischémique (p=0.049, RR 3.13, 95% IC 1.01-10.0) constituaient tous des prédicteurs indépendant de mortalité. Une régurgitation mitrale persistante au 7 e jour post-opératoire (p= 0.005, RR 4.55, 95 % IC :1.56 -20.0), un âge inférieur à 60 ans (p = 0.012, RR 8.7, 95 % IC 2.44 - 37.8) et l'absence d'anneau prothétique (p = 0.034, RR 4.76, 95 % IC 1.79-33.3) se sont tous révélés être des facteurs de risque indépendant de réopération. Conclusion: Les réparations mitrales sont accompagnées d'une excellente survie à long terme même si leur évolution peut être influencée négativement par de nombreux facteurs de risques periopératoires. Les risques de réopération sont plus élevés chez des patients jeunes présentant une régurgitation mitrale résiduelle et n'ayant pas bénéficié de la mise en place d'un anneau prothétique.

The role of the Estrogen-Responsive B box protein in skin morphogenesis, wound repair and skin disease

SUMMARY: EBBP is a poorly characterized member of the RBCC/TRIM family (RING finger B-box coiled-coilltripartite motif). It is ubiquitously expressed, but particularly high levels are found in keratinocytes. There is evidence that EBBP is involved in inflammatory processes, since it can interact with pro-interleukin-1 ß (prolL-1 ß) in human macrophages and keratinocytes, and its downregulation results in reduced secretion of IL-1 ß. IL-1ß activation and secretion requires the proteolytic cleavage of prolL-1ß by caspase-1, which in turn is actìvated by a protein complex called the inflammasome. As it has been demonstrated that EBBP can bind two different proteins of the inflammasome (NALP-1 and caspase 1), we assumed that EBBP plays a role in the regulation of inflammation and that the inflammasome, which has as yet only been described in ínflammatory cells, may also exist in keratinocytes. Indeed, I could show in my thesis that the inflammasome components are expressed in human keratinócytes at the RNA and protein level and also in vivo in human epidermis. After irradiation with a physiological dose of UVB, keratinocytes activated prolL-1ß and secreted prolL-1 a, IL-1 ß, prolL-18 and inflammasome proteins, although all these proteins lack a classical signal peptide. The secretion was dependent on caspase-1 activity, but not on de novo protein synthesis. Knock-down of NALP1 and -3, caspase-1 and -5, EBBP and Asc strongly reduced the secretion of IL-1 ß, demonstrating that also in keratinocytes inflammasome proteins are directly involved in maturation of this cytokine. These results demonstrate for the first time the presence of an active inflammasome in non-professional immune cells. Moreover, they show that UV irradiation is a stimulus for inflammasome activation in keratinocytes. For the analysis of the ín vivo functions of EBBP, transgenic mice overexpressing EBBP in the epidermis were generated. To examine the influence of EBBP overexpression on inflammatory processes, we subjected the mice to different challenges, which induce inflammation. Wound-healing, UVB irradiation and delayed hypersensitivity were tested, but we did not observe any phenotype in the K14-EBBP mice. Besides, a conditional ebbp knockout mouse has been obtained, which will allow to determine the effects of EBBP gene deletion in different tissues and organs. RESUME: EBBP est un membre encore mal connu de la famille des RBCC/TRIM (RING finger B-box coiled-coil/tripartite motif). Il est exprimé de manière ubiquitaire, et en particulier dans les kératinocytes. EBBP étant capable d'interagir avec la prointerleukine-1 ß (prolL-1 ß) dans les macrophages et les kératinocytes humains et de réguler la sécrétion de l'IL-1 ß, il est très probable que cette protéine est impliquée dans l'inflammation. L'activation et la sécrétion de l'IL-1 ß requièrent le clivage protéolytique de son précurseur prolL-1ß par la caspase-1, qui est elle-même activée par un complexe protéique appelé l'inflammasome. Comme il a été démontré qu'EBBP peut lier deux protéines de l'inflammasome (NALP-1 et caspase-1), nous avons émis l'hypothèse qu'EBBP joue un rôle dans la régulation de l'inflammation et que l'inflammasome, jusqu'ici décrit exclusivement dans des cellules inflammatoires, existe dans les kératinocytes. En effet, j'ai pu montrer dans ma thèse que les composants de l'inflammasome sont exprimés dans les kératinocytes humains ainsi que in vivo dans l'épiderme humain. Après irradiation avec une dose, physiologique d'UVB, les kératinocytes activent la prolL-1 ß et sécrètent la prolL-1a, l'IL-1 ß, la prolL-18 et des protéines de l'inflammasome, bien que toutes ces protéines soient dépourvues de peptide signal. La sécrétion dépend de la caspase-1 mais pas de la synthèse protéique de novo. Le knock-down de NALP-1 et -3, des caspase-1 et -5, d'EBBP et d'Asc réduit de manière marquée la sécrétion d'IL-1 ß, démontrant que dans les kératinocytes également, les protéines de l'inflammasome sont impliquées directement dans la maturation de cette cytokine. Ces résultats démontrent pour la première fois la présence d'un inflammasome actif dans des cellules immunitaires non professionnelles. De plus, ils montrent que l'irradiation aux UV est un stimulus pour l'activation de l'inflammasome dans les kératinocytes. Pour l'analyse des fonctions d'EBBP in vivo, nous avons généré des souris transgéniques qui surexpriment EBBP dans l'épiderme. En vue d'examiner l'influence de la surexpression d'EBBP sur le processus inflammatoire, nous avons soumis ces souris à differents modèles d'inflammation. Nous avons testé cicatrisation, UVB et hypersensibilité retardée, mais n'avons pas observé de phénotype chez les souris transgéniques. En parallèle, nous avons également généré des souris knock-out pour ebbp qui devraient nous permettre de déterminer les effets de la suppression d'EBBP dans différents tissus et organes.

Fibrin sealant for mesh fixation in endoscopic inguinal hernia repair: is there enough evidence for its routine use?

Fibrin sealing has recently evolved as a new technique for mesh fixation in endoscopic inguinal hernia repair. A comprehensive Medline search was carried out evaluating fibrin sealant for mesh fixation, and finally 12 studies were included (3 randomized trials, 3 nonrandomized trials, and 6 case series). The trials were assessed for operative time, seroma formation, recovery time, recurrence rate, and acute and chronic pain.There was a trend toward decreased operative times for fibrin sealing compared with mechanical stapling; however, the results for seroma formation remained contradictory. The most important finding was the reduced postoperative pain. Recovery times were lower after fibrin sealing and the recurrence rates showed no differences.Fibrin sealing for mesh fixation in the endoscopic inguinal hernia surgery is a promising alternative to mechanical stapling, which can be safely applied. As the overall quality of published data remains poor, further well-designed studies are needed until fibrin sealing can replace mechanical stapling as a new standard for mesh fixation.

Accessory tendinous slips arising from the extensor carpi ulnaris (ECU) tendon: MRI appearance, prevalence and association with ECU tenosynovitis and tendinopathy

Purpose: To report the MRI features of ECU accessory tendinous slips, assess their observable prevalence and evaluate a potential link between this anatomical variation and ECU tenosynovitis or tendinopathy. Methods and materials: Institutional review board approved this retrospective study, with waiver of patient informed consent. One hundred sixty wrist MRI studies from 158 patients (85 females, 73 males, mean age 45.6 years, range 14-86) performed between March 2008 and February 2009 on a 1.5-T unit were included. MR images were analyzed by two radiologists in consensus. The observable prevalence of ECU accessory tendinous slips was assessed and their origin, diameter and insertion sites were noted. The presence of ECU tenosynovitis and/or tendinopathy was also evaluated. Results: The observable prevalence of ECU accessory tendinous slips was 21.9% (35/160). The origin was always seen: 8 were at the level of, and 27 distal to the ECU subsheath. The slip median diameter was 0.67 mm (range 0.43-0.88). The insertion was seen in 17.1% (6/35): 2 were on the fifth metacarpal bone, 4 on the extensor apparatus of the fifth finger. ECU tenosynovitis (20%), tendinopathy (5.7%) as well as concomitant tenosynovitis and tendinopathy (25.7%) were more frequently encountered in the patients with the anatomical variation than in the control patients group (0.8%, 3.2% and 9.6% respectively). Differences were statistically significant for tenosynovitis (p = 0.0001) and concomitant tenosynovitis and tendinopathy (p = 0.02) of the ECU. Conclusion: ECU accessory tendinous slips are frequent and visible on 1.5-T wrist MRI studies. ECU tenosynovitis and tendinopathy are more frequent in patients bearing this anatomical variation.

Questioning the utility of RNA-DNA chimera in gene repair.

In principle, we should be glad that Eric Kmiec and his colleagues published in Science's STKE (1) a detailed experimental protocol of their gene repair method (2, 3). However, a careful reading of their contribution raises more doubts about the method. The research published in Science five years ago by Kmiec and his colleagues was said to demonstrate that chimeric RNA-DNA oligonucleotides could correct the mutation responsible for sickle cell anemia with 50% efficiency (4). Such a remarkable result prompted many laboratories to attempt to replicate the research or utilize the method on their own systems. However, if the method worked at all, which it rarely did, the achieved efficiency was usually lower by several orders of magnitude. Now, in the Science's STKE protocol, we are given crucial information about the method and why it is so important to utilize these expensive chimeric RNA-DNA constructs. In the introduction we are told that the RNA-DNA duplex is more stable than a DNA-DNA duplex and so extends the half-life of the complexes formed between the targeted DNA and the chimeric RNA-DNA oligonucleotides. This logical explanation, however, conflicts with the statement in the section entitled "Transfection with Oligonucleotides and Plasmid DNA" that Kmiec and colleagues have recently demonstrated that classical single-stranded DNA oligonucleotides with a few protective phosphothioate linkages have a "gene repair conversion frequency rivaling that of the RNA/DNA chimera". Indeed, the research cited for that result actually states that single-stranded DNA oligonucleotides are in fact several-fold more efficient (3.7-fold) than the RNA-DNA chimeric constructs (5). If that is the case, it raises the question of why Kmiec and colleagues emphasize the importance of the RNA in their original chimeric constructs. Their own new results show that modified single-stranded DNA oligonucleotides are more effective than the expensive RNA-DNA hybrids. Moreover, the current efficiency of the gene repair by RNA-DNA hybrids, according to Kmiec and colleagues in their recent paper is only 4×10-4 even after several hours of pre-selection permitting multiplification of bacterial cells with the corrected plasmid (5). This efficiency is much lower than the 50% value reported five years ago, but is assuredly much closer to the reality.

Repair of non-circumferential cervical trachea defects by three different latissimus dorsi flaps. A comparative studyin an experimental setting.

BACKGROUND: Large intrathoracic airway defects may be closed using a pedicled latissimus dorsi (LD) flap, with rewarding results. This study addresses the question of whether this holds true for extrathoracic non-circumferential tracheal defects. METHODS: A cervical segment of the trachea of 4 x 1 cm was resected in 9 white male pigs. The defect was stented with a silicone stent for 3 months and closed either by an LD flap alone (group a, n = 3), an LD flap with an attached rib segment covered by pleura (group b, n = 3), or an LD flap reinforced by a perforated polylactide (MacroPore) plate (group c, n = 3). The trachea was assessed by rigid endoscopy at 3 and 4 months and histologically at 4 months postoperatively. RESULTS: The degree of stenosis at the level of the reconstruction at 4 months was 25, 50 and 75% in group a, 15, 50 and 60% in group b, and 20, 95 and 95% in group c, respectively. The percentage of the defect covered by columnar epithelium was 100% in all animals of group a, 60, 100 and 100% in group b, and 10, 0 and 0% in group c. Resorption of the rib was seen in all animals of group b and obstructive inflammatory polyps were found in 2 animals of group c. CONCLUSION: Pedicled LD flaps provided less satisfactory results for closure of large non-circumferential extrathoracic airway defects than observed after intrathoracic reconstruction. A pedicled rib segment added to the LD flap did not improve the results obtained from LD flap repair alone, and an embedded MacroPore prosthesis may result in severe airway stenosis due to plate migration and intense inflammatory reaction protruding into the tracheal lumen.

Role of BRCA2 in control of the RAD51 recombination and DNA repair protein.

Individuals carrying BRCA2 mutations are predisposed to breast and ovarian cancers. Here, we show that BRCA2 plays a dual role in regulating the actions of RAD51, a protein essential for homologous recombination and DNA repair. First, interactions between RAD51 and the BRC3 or BRC4 regions of BRCA2 block nucleoprotein filament formation by RAD51. Alterations to the BRC3 region that mimic cancer-associated BRCA2 mutations fail to exhibit this effect. Second, transport of RAD51 to the nucleus is defective in cells carrying a cancer-associated BRCA2 truncation. Thus, BRCA2 regulates both the intracellular localization and DNA binding ability of RAD51. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.