Differentiating normal hyaline cartilage from post-surgical repair tissue using fast gradient echo imaging in delayed gadolinium-enhanced MRI (dGEMRIC) at 3 Tesla

The purpose was to evaluate the relative glycosaminoglycan (GAG) content of repair tissue in patients after microfracturing (MFX) and matrix-associated autologous chondrocyte transplantation (MACT) of the knee joint with a dGEMRIC technique based on a newly developed short 3D-GRE sequence with two flip angle excitation pulses. Twenty patients treated with MFX or MACT (ten in each group) were enrolled. For comparability, patients from each group were matched by age (MFX: 37.1 +/- 16.3 years; MACT: 37.4 +/- 8.2 years) and postoperative interval (MFX: 33.0 +/- 17.3 months; MACT: 32.0 +/- 17.2 months). The Delta relaxation rate (DeltaR1) for repair tissue and normal hyaline cartilage and the relative DeltaR1 were calculated, and mean values were compared between both groups using an analysis of variance. The mean DeltaR1 for MFX was 1.07 +/- 0.34 versus 0.32 +/- 0.20 at the intact control site, and for MACT, 1.90 +/- 0.49 compared to 0.87 +/- 0.44, which resulted in a relative DeltaR1 of 3.39 for MFX and 2.18 for MACT. The difference between the cartilage repair groups was statistically significant. The new dGEMRIC technique based on dual flip angle excitation pulses showed higher GAG content in patients after MACT compared to MFX at the same postoperative interval and allowed reducing the data acquisition time to 4 min.

Evaluation and comparison of cartilage repair tissue of the patella and medial femoral condyle by using morphological MRI and biochemical zonal T2 mapping

The objective of this study was to use advanced MR techniques to evaluate and compare cartilage repair tissue after matrix-associated autologous chondrocyte transplantation (MACT) in the patella and medial femoral condyle (MFC). Thirty-four patients treated with MACT underwent 3-T MRI of the knee. Patients were treated on either patella (n = 17) or MFC (n = 17) cartilage and were matched by age and postoperative interval. For morphological evaluation, the MR observation of cartilage repair tissue (MOCART) score was used, with a 3D-True-FISP sequence. For biochemical assessment, T2 mapping was prepared by using a multiecho spin-echo approach with particular attention to the cartilage zonal structure. Statistical evaluation was done by analyses of variance. The MOCART score showed no significant differences between the patella and MFC (p > or = 0.05). With regard to biochemical T2 relaxation, higher T2 values were found throughout the MFC (p < 0.05). The zonal increase in T2 values from deep to superficial was significant for control cartilage (p < 0.001) and cartilage repair tissue (p < 0.05), with an earlier onset in the repair tissue of the patella. The assessment of cartilage repair tissue of the patella and MFC afforded comparable morphological results, whereas biochemical T2 values showed differences, possibly due to dissimilar biomechanical loading conditions.

The clinical and structural long-term results of open repair of massive tears of the rotator cuff

BACKGROUND: At a mean follow-up of 3.1 years, twenty-seven consecutive repairs of massive rotator cuff tears yielded good and excellent clinical results despite a retear rate of 37%. Patients with a retear had improvement over the preoperative state, but those with a structurally intact repair had a substantially better result. The purpose of this study was to reassess the same patients to determine the long-term functional and structural results. METHODS: At a mean follow-up interval of 9.9 years, twenty-three of the twenty-seven patients returned for a review and were examined clinically, radiographically, and with magnetic resonance imaging with use of a methodology identical to that used at 3.1 years. RESULTS: Twenty-two of the twenty-three patients remained very satisfied or satisfied with the result. The mean subjective shoulder value was 82% (compared with 80% at 3.1 years). The mean relative Constant score was 85% (compared with 83% at 3.1 years). The retear rate was 57% at 9.9 years (compared with 37% at 3.1 years; p = 0.168). Patients with an intact repair had a better result than those with a failed reconstruction with respect to the mean absolute Constant score (81 compared with 64 points, respectively; p = 0.015), mean relative Constant score (95% and 77%; p = 0.002), and mean strength of abduction (5.5 and 2.6 kg; p = 0.007). The mean retear size had increased from 882 to 1164 mm(2) (p = 0.016). Supraspinatus and infraspinatus muscle fatty infiltration had increased (p = 0.004 and 0.008, respectively). Muscles with torn tendons preoperatively showed more fatty infiltration than muscles with intact tendons preoperatively, regardless of repair integrity. Shoulders with a retear had a significantly higher mean acromion index than those without retear (0.75 and 0.65, respectively; p = 0.004). CONCLUSIONS: Open repair of massive rotator cuff tears yielded clinically durable, excellent results with high patient satisfaction at a mean of almost ten years postoperatively. Conversely, fatty muscle infiltration of the supraspinatus and infraspinatus progressed, and the retear size increased over time. The preoperative integrity of the tendon appeared to be protective against muscle deterioration. A wide lateral extension of the acromion was identified as a previously unknown risk factor for retearing.

Mechano-regulated tenascin-C orchestrates muscle repair

Tenascin-C (TNC) is a mechano-regulated, morphogenic, extracellular matrix protein that is associated with tissue remodeling. The physiological role of TNC remains unclear because transgenic mice engineered for a TNC deficiency, via a defect in TNC secretion, show no major pathologies. We hypothesized that TNC-deficient mice would demonstrate defects in the repair of damaged leg muscles, which would be of functional significance because this tissue is subjected to frequent cycles of mechanical damage and regeneration. TNC-deficient mice demonstrated a blunted expression of the large TNC isoform and a selective atrophy of fast-muscle fibers associated with a defective, fast myogenic expression response to a damaging mechanical challenge. Transcript profiling mapped a set of de-adhesion, angiogenesis, and wound healing regulators as TNC expression targets in striated muscle. Expression of these regulators correlated with the residual expression of a damage-related 200-kDa protein, which resembled the small TNC isoform. Somatic knockin of TNC in fast-muscle fibers confirmed the activation of a complex expression program of interstitial and slow myofiber repair by myofiber-derived TNC. The results presented here show that a TNC-orchestrated molecular pathway integrates muscle repair into the load-dependent control of the striated muscle phenotype.

Coupling of mutated Met variants to DNA repair via Abl and Rad51

Abnormal activation of DNA repair pathways by deregulated signaling of receptor tyrosine kinase systems is a compelling likelihood with significant implications in both cancer biology and treatment. Here, we show that due to a potential substrate switch, mutated variants of the receptor for hepatocyte growth factor Met, but not the wild-type form of the receptor, directly couple to the Abl tyrosine kinase and the Rad51 recombinase, two key signaling elements of homologous recombination-based DNA repair. Treatment of cells that express the mutated receptor variants with the Met inhibitor SU11274 leads, in a mutant-dependent manner, to a reduction of tyrosine phosphorylated levels of Abl and Rad51, impairs radiation-induced nuclear translocation of Rad51, and acts as a radiosensitizer together with the p53 inhibitor pifithrin-alpha by increasing cellular double-strand DNA break levels following exposure to ionizing radiation. Finally, we propose that in order to overcome a mutation-dependent resistance to SU11274, this aberrant molecular axis may alternatively be targeted with the Abl inhibitor, nilotinib.

Postoperative hypoesthesia and pain: qualitative assessment after open and laparoscopic inguinal hernia repair

BACKGROUND: Chronic pain is an important outcome variable after inguinal hernia repair that is generally not assessed by objective methods. The aim of this study was to objectively investigate chronic pain and hypoesthesia after inguinal hernia repair using three types of operation: open suture, open mesh, and laparoscopic. METHODS: A total of 96 patients were included in the study with a median follow-up of 4.7 years. Open suture repair was performed in 40 patients (group A), open mesh repair in 20 patients (group B), and laparoscopic repair in 36 patients (group C). Hypoesthesia and pain were assessed using von Frey monofilaments. Quality of life was investigated with Short Form 36. RESULTS: Pain occurring at least once a week was found in 7 (17.5%) patients of group A, in 5 (25%) patients of group B, and in 6 (16.6%) patients of group C. Area and intensity of hyposensibility were increased significantly after open nonmesh and mesh repair compared to those after laparoscopy (p = 0.01). Hyposensibility in patients who had laparoscopic hernia repair was significantly associated with postoperative pain (p = 0.03). Type of postoperative pain was somatic in 19 (61%), neuropathic in 9 (29%), and visceral in 3 (10%) patients without significant differences between the three groups. CONCLUSIONS: The incidence of hypoesthesia in patients who had laparoscopic hernia repair is significantly lower than in those who had open hernia repair. Hypoesthesia after laparoscopic but not after open repair is significantly associated with postoperative pain. Von Frey monofilaments are important tools for the assessment of inguinal hypoesthesia and pain in patients who had inguinal hernia repair allowing quantitative and qualitative comparison between various surgical techniques.

Dynamic repair of scapholunate dissociation with dorsal extensor carpi radialis longus tenodesis

This study investigates the results of a technique using an extensor carpi radialis longus (ECRL) tenodesis for symptomatic scapholunate instability. Symptomatic scapholunate instability has been corrected so far either by limited wrist fusion or by various techniques of soft tissue repair. Limited wrist fusion greatly reduces wrist motion and increases the probability of osteoarthritis in the remaining mobile wrist segments. On the other hand, most types of soft tissue repair are technically difficult to perform and have disappointing results due to the inherent laxity. The presented dynamic approach was used in 20 wrists of 19 patients with static scapholunate instability. Preoperative evaluation included in all patients clinical examination, radiologic evaluation, and arthroscopy for establishing the diagnosis of static scapholunate instability. The technique involves the fixation of the ECRL tendon on the dorsal aspect of the scaphoid by means of a cancellous screw and a special washer. Dynamic ECRL tenodesis of the scaphoid is a safe and simple procedure that enhances the extension forces on the scaphoid in all wrist positions. The results of this preliminary report in 20 wrists showed dynamic ECRL tenodesis to be an effective treatment option for treating symptomatic static scapholunate instability.

Microsurgical repair of the sural nerve after nerve biopsy to avoid associated sensory morbidity: a preliminary report

OBJECTIVE: The purpose of this article is to report our preliminary results regarding microsurgical repair of the sural nerve after nerve biopsy, in an attempt to reduce the well-described sensory morbidity and neuroma formation. METHODS: Three patients with a suspected diagnosis of peripheral neuropathy underwent sural nerve biopsies to establish definitive diagnoses. A 10-mm segment of the sural nerve was resected with local anesthesia. After harvesting of the specimen, the proximal and distal nerve stumps were carefully mobilized and united with epineural suture techniques, under a surgical microscope. Sensory evaluations (assessing the presence of hypesthesia/dysesthesia or pain) of the lateral aspect of the foot, in regions designated Areas 1, 2, and 3, were performed before and 6 and 12 months after the biopsies. A visual analog scale was used for pain estimation. RESULTS: The biopsy material was sufficient for histopathological examinations in all cases, leading to conclusive diagnoses (vasculitis in two cases and amyloidosis in one case). The early post-biopsy hypesthesia, which was present for 4 to 8 weeks, improved to preoperative levels as early as 6 months after the nerve repair. Sensory evaluations performed at 6- and 12-month follow-up times demonstrated that none of the patients complained of pain at the biopsy site or distally in the area innervated by the sural nerve. Ultrasonography performed at the 12-month follow-up examination revealed normal sural nerve morphological features, with no neuroma formation, comparable to findings for the contralateral site. CONCLUSION: Microsurgical repair of the sural nerve after biopsy can eliminate or reduce sensory disturbances such as paraesthesia, hypesthesia, and dysesthesia distal to the biopsy site, in the distribution of the sensory innervation of the sural nerve, and can prevent painful neuroma formation. To our knowledge, this article is the first in the literature to report on microsurgical repair of the sural nerve after nerve biopsy. Decreased side effects suggest that this technique can become a standard procedure after sural nerve biopsy, which is commonly required to establish the diagnosis of various diseases, such as peripheral nerve pathological conditions, vasculitis, and amyloidosis. More cases should be analyzed, however, to explore the usefulness of the technique and the reliability of sural nerve biopsy samples in attempts to obtain conclusive diagnoses.

Prospective, intraindividual comparison of MRI versus MDCT for endoleak detection after endovascular repair of abdominal aortic aneurysms

This study compares MRI and MDCT for endoleak detection after endovascular repair of abdominal aortic aneurysms (EVAR). Forty-three patients with previous EVAR underwent both MRI (2D T1-FFE unenhanced and contrast-enhanced; 3D triphasic contrast-enhanced) and 16-slice MDCT (unenhanced and biphasic contrast-enhanced) within 1 week of each other for endoleak detection. MRI was performed by using a high-relaxivity contrast medium (gadobenate dimeglumine, MultiHance). Two blinded, independent observers evaluated MRI and MDCT separately. Consensus reading of MRI and MDCT studies was defined as reference standard. Sensitivity, specificity, and accuracy were calculated and Cohen's k statistics were used to estimate agreement between readers. Twenty endoleaks were detected in 18 patients at consensus reading (12 type II and 8 indeterminate endoleaks). Sensitivity, specificity, and accuracy for endoleak detection were 100%, 92%, and 96%, respectively, for reader 1 (95%, 81%, 87% for reader 2) for MRI and 55%, 100%, and 80% for reader 1 (60%, 100%, 82% for reader 2) for MDCT. Interobserver agreement was excellent for MDCT (k = 0.96) and good for MRI (k = 0.81). MRI with the use of a high-relaxivity contrast agent is significantly superior in the detection of endoleaks after EVAR compared with MDCT. MRI may therefore become the preferred technique for patient follow-up after EVAR.

Estrogen-stimulated endothelial repair requires osteopontin

OBJECTIVE: Estradiol (E(2)) is known to accelerate reendothelialization and thus prevent intimal thickening and in-stent restenosis after angioplasty. Transplantation experiments with ERalpha(-/-) mice have previously shown that E(2) acts through local and bone marrow cell compartments to enhance endothelial healing. However, the downstream mechanisms induced by E(2) to mediate endothelial repair are still poorly understood. METHODS AND RESULTS: We show here that after endovascular carotid artery injury, E(2)-enhanced endothelial repair is lost in osteopontin-deficient mice (OPN(-/-)). Transplantation of OPN(-/-) bone marrow into wild-type lethally irradiated mice, and vice versa, suggested that osteopontin plays a crucial role in both the local and the bone marrow actions of E(2). In the vascular compartment, using transgenic mice expressing doxycyclin regulatable-osteopontin, we show that endothelial cell specific osteopontin overexpression mimics E(2)-enhanced endothelial cell migration and proliferation in the regenerating endothelium. In the bone marrow cell compartment, we demonstrate that E(2) enhances bone marrow-derived mononuclear cell adhesion to regenerating endothelium in vivo, and that this effect is dependent on osteopontin. CONCLUSIONS: We demonstrate here that E(2) acceleration of the endothelial repair requires osteopontin, both for bone marrow-derived cell recruitment and for endothelial cell migration and proliferation.

Thoracic endovascular aortic repair: impact of urgency on outcome and quality of life

OBJECTIVES: Endovascular repair of the descending thoracic aorta is a very promising technique in elective and, particularly, emergency situations. This study assessed the impact of urgency of the procedure on outcome and mid-term quality of life in surviving patients. METHODS: Post hoc analysis of prospectively collected data of 58 consecutive patients (January 2001-December 2005) with surgical pathologies of the descending thoracic aorta treated by endovascular means. Six patients were excluded due to recent operations on the ascending aorta before thoracic endovascular repair. The remaining patients (n=52) were 69+/-10 years old, and 43 were men (83%). Twenty-seven had been treated electively, and 25 for emergency indications. Reasons for emergency were acute type B aortic dissections with or without malperfusion syndrome in 14, and aortic ruptures in 11 cases. Follow-up was 29+/-16 months. Endpoints were perioperative and late morbidity and mortality rates and long-term quality of life as assessed by the short form health survey (SF-36) and Hospital Anxiety and Depression Scale questionnaires. RESULTS: Cohorts were comparable regarding age, sex, cardiovascular risk factors, and comorbidities. Perioperative mortality was somewhat higher in emergency cases (12% vs 4%, p=0.34). Paraplegia occurred in one patient in each cohort (4%). Overall quality of life after two and a half years was similar in both treatment cohorts: 72 (58-124) after emergency, and 85 (61-105) after elective endovascular aortic repair (p=0.98). Normal scores range from 85 to 115. Anxiety and depression scores were in the normal range and comparable. CONCLUSIONS: Thoracic endovascular aortic repair is an excellent and safe treatment option for the diseased descending aorta, particularly in emergency situations. Early morbidity and mortality rates can be kept very low. Mid-term quality of life was not affected by the urgency of the procedure. Similarly, mid-term anxiety and depression scores were not increased after emergency situations.