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Objectives: Few data are available to describe the changes in incidence of pediatric-onset inflammatory bowel disease (IBD). The aim of this study was to describe changes in incidence and phenotypic presentation of pediatric-onset IBD in northern France during a 24-year period., Methods: Pediatric-onset IBD (<17 years) was issued from a population-based IBD study in France between 1988 and 2011. Age groups and digestive location were defined according to the Paris classification., Results: 1,350 incident cases were recorded (8.3% of all IBD) including 990 Crohn's disease (CD), 326 ulcerative colitis (UC) and 34 IBD unclassified (IBDU). Median age at diagnosis was similar in CD (14.4 years (Q1=11.8-Q3=16.0)) and UC (14.0 years (11.0-16.0)) and did not change over time. There were significantly more males with CD (females/males=0.82) than UC (females/males=1.25) (P=0.0042). Median time between onset of symptoms and IBD diagnosis was consistently 3 months (1-6). Mean incidence was 4.4/10 5 for IBD overall (3.2 for CD, 1.1 for UC and 0.1 for IBDU). From 1988-1990 to 2009-2011, a dramatic increase in incidences of both CD and UC were observed in adolescents (10-16 years): for CD from 4.2 to 9.5/10 5 (+126%; P<0.001) and for UC, from 1.6 to 4.1/10 5 (+156%; P<0.001). No modification in age or location at diagnosis was observed in either CD or UC., Conclusions: In this population-based study, CD and UC incidences increased dramatically in adolescents across a 24-year span, suggesting that one or more strong environmental factors may predispose this population to IBD.

Background: Despite the benefit of safety vests to the reduction of torso injuries in children and adolescents is unclear, its' use is recommended. The aim of the present study is to determine the effectiveness of safety vests actually used in pediatric equestrian activities., Patients and Method: In this case-control-study, we analyzed the accidents of 92 riders aged 18 or younger who fell off a horse onto his/her torso during a period of 18 months. Data were gathered from the clinical records. Additionally, a questionnaire was administered on the day of trauma by the patients and/or their parents., Results: The cases comprised 31 patients who sustained torso injuries. The controls were 61 riders with injuries of other body parts than to the torso. Safety vest use was not associated with a lower risk of torso injuries (OR=1.18, 95% CI (0.50, 2.81), p=0.707). Post hoc power analysis revealed that within such a setting an odds ratio of 0.266 could be found with a power of 80%., Conclusion: This study is not able to show an association between wearing a torso protector and protection from torso injuries, probably due to confounding. We did not detect a high effect of safety vest usage in our study population. Whether the development of a new generation of safety vests might be more effective remains unclear. An effective vest should be adapted to the requirements of children and adolescents and should protect the thorax and abdomen, but also the cervical and the lumbar spine., (© Georg Thieme Verlag KG Stuttgart · New York.)

This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor.

In this retrospective cross-sectional study, we contacted patients who had been diagnosed with (and, if necessary, treated for) knee cartilage defects by arthroscopy at one of seven treatment centres in Germany between 1997 and 2001. In early 2003, patients completed a questionnaire on the health care resources they had used since the time of the arthroscopy. Based on this information, we determined follow-up costs. Data from a total of 1,708 patients were included in the final analysis. Of these, 1,070 were assigned to the initial operation (IO) group (61% men, 49+/-15 years; 39% women, 52+/-14 years) and 638 were assigned to the re-operation (RO) group (64% men, 44+/-13 years; 36% women, 47+/-14 years). The cumulative direct medical costs caused by knee complaints for the first 5 years following the arthroscopy were 1,984 Euro for the IO population and 4,203 Euro for the RO population. The cumulative indirect costs (i.e. costs associated with loss of productivity), however, amounted to 7,669 Euro and 15,265 Euro, respectively, and were thus almost four times as high as the cumulative direct costs. This is the first study that quantifies the considerable follow-up costs in patients who have undergone surgery for knee cartilage defects. As such, it may provide a yardstick for future treatments.

Complications after shoulder arthrodesis are frequent. Through results and comparisons with the literature, the presented article analyzes the correlation of complications with the specific operative techniques, indications, and postoperative treatment. Between 1964 and 2001, a total of 43 cases of shoulder arthrodesis (13 screw and 30 plate arthrodeses) were performed and then analyzed after a mean of 6.7 years (range, 0.5-36 years). Surgery was carried out on 10 female patients (23%) and 33 male patients (77%) with a mean age of 35 years (range, 11-82 years). These patients had the following indications: paralysis (32 [74%]), osteoarthritis or humeral head necrosis (15 [35%]), infection (7 [16%]), and persistent shoulder instability (6 [14%]). The extent of active movement after arthrodesis was 56 degrees abduction (range, 20 degrees - 90 degrees) and 60 degrees forward flexion (range, 20 degrees - 105 degrees), with an increase in the Constant score in all cases, from a mean of 27 points preoperatively to 57 points postoperatively (difference, 30 points). The patients rated the outcome of surgery as excellent, good, or satisfactory in 91% of cases. Complications after shoulder arthrodesis were noted in 12 of 43 patients (28%). The most frequent complications after screw/plate arthrodesis included pseudarthrosis, 2 (15%)/3 (10%); infection, 1 (8%)/4 (13%); and fracture of the humerus, 0/4 (13%). No specific judgment can be attributed to the different osteosynthesis techniques used in shoulder arthrodesis, either in the cases presented at our clinic or in the literature. Pseudarthrosis appeared to be less frequent in cases of plate arthrodesis compared with screw arthrodesis. However, the application of plates resulted more often in infection, postoperative fractures of the humerus, and the necessity for removal of material. Particularly in patients with paralysis, a shoulder arthrodesis resulted in an improvement in postoperative active function and presented a suitable operative option.

MEK1 and MEK2 are closely related, dual-specificity tyrosine/threonine protein kinases found in the Ras/Raf/MEK/ERK mitogen-activated protein kinase (MAPK) signaling pathway. Approximately 30% of all human cancers have a constitutively activated MAPK pathway, and constitutive activation of MEK1 results in cellular transformation. Here we present the X-ray structures of human MEK1 and MEK2, each determined as a ternary complex with MgATP and an inhibitor to a resolution of 2.4 A and 3.2 A, respectively. The structures reveal that MEK1 and MEK2 each have a unique inhibitor-binding pocket adjacent to the MgATP-binding site. The presence of the potent inhibitor induces several conformational changes in the unphosphorylated MEK1 and MEK2 enzymes that lock them into a closed but catalytically inactive species. Thus, the structures reported here reveal a novel, noncompetitive mechanism for protein kinase inhibition.

Objective: We aimed to investigate temperature distribution during laser and its possible thermal damage to the neurovascular structures., Background Data: Percutaneous laser disc decompression (PLDD) is now being performed as a minimally invasive intradiscal technique for the operative therapy of non-sequestered herniated cervical discs. As yet, no experimental basic research has been reported with regard to temperature rise and distribution in the cervical region during laser radiation., Materials and Methods: An in vitro laser procedure was performed on human cervical intervertebral discs under standardized conditions. A thermo-camera was used to monitor in real-time the zones sensitive to temperature increase., Results: Average intervertebral disc volume was 2000 mm3. With a total energy conduction of 600 Joules, a temperature increase of around 30 degrees C was shown with an initial temperature of 28 degrees C at the posterior longitudinal ligament lying immediately in front of the myelon. The defect volume was less than 1% of the total intervertebral disc volume., Conclusion: If, during laser application, the total amount of conducted energy is too high, with an unfavorable position of the fibers in the intervertebral space, there is a risk of thermal damage to the spinal cord and nerve roots.

Limited function due to paralysis following brachial plexus lesions can be improved by secondary operations of the bony and soft tissue. Between April 1994 and December 2000, 109 patients suffering from arm-plexus lesions underwent a total of 144 reconstructive operations guided by our concept of integrated therapy. The average age at the time of surgery was 32 years (range: 15-59). The following operations were performed: shoulder arthrodesis (23), trapezius transfer (74), rotation osteotomy of humerus (9), triceps to biceps transposition (9), transposition of forearm flexors or extensors (8), latissimus transfer (7), pectoralis transfer (1), teres major transfer (1), transposition of flexor carpi ulnaris to the tendons of extensor digitorum (10), and wrist arthrodesis (2). Prospectively, in all patients, the grade of muscle power of the affected upper extremity was evaluated prior to surgery. The follow-up period for all 144 operations was, on average, 22 months (range: 6-74). By means of operative measures, almost all patients obtained an improvement of shoulder function (100%) and stability (>90%), elbow flexion (85%), and hand, finger, and thumb (100%). When muscles malfunction after brachial plexus lesions, one should take into account the individual neuromuscular defect, passive joint function, and bony deformities; different procedures such as muscle transpositions, arthrodeses, and corrective osteotomies can then be performed to improve function of the upper extremity. Each form of operative treatment presents patients with certain benefits and all are integrated into a total treatment plan for the affected extremity.

Malfunction of the infraspinatus muscle and teres minor muscle illustrate the typical clinical picture in patients with brachial plexus palsy. The arm hangs down in an inwardly rotated position and elbow flexion is hindered by striking of the lower arm against the thorax. Between 1995 and 2000, we have done external rotational osteotomy of the humerus for nine patients with brachial plexus palsy. The mean age of the patients at the time of operation was 29 years (range 15 to 42). The mean follow-up time was 24 (6 to 69) months. Preoperatively, the patients all had appreciable deficits of external rotation (mean deficit 37 degrees, range 10 degrees to 70 degrees). As a result of osteotomy, external rotation was improved in all patients, the mean increase being 42 degrees (range 25 degrees to 60 degrees). All patients were subjectively content with the improved position of the arm and its function. They were able to move their hands to their faces without striking the lower arm against the chest on elbow flexion, or without compensatory evasive movement of the shoulder.

In an adult, a marked deformity of the upper arm and forearm with loss of function of the limb due to obstetrical brachial plexus palsy has been corrected. An external rotational osteotomy of the humerus and radioulnar arthrodesis resulted in an improved function.

Arthrodesis of the hindfoot is indicated in congenital foot deformity of young adults, in posttraumatic arthrosis of the subtalar joint following calcaneus fractures, in idiopathic, isolated arthroses of hindfoot joints, in rheumatoid arthritis and in deformities of the longitudinal arch of the foot. Common and useful combinations are the triple-arthrodesis and the arthrodesis of the subtalar and the calcaneocuboid joint, in particular if both joints are affected by calcaneus fractures. Arthrodesis of the subtalar and the talonavicular joint are often performed as isolated procedures. The three-dimensional structure of the hindfoot articulations may impede perfect contact of the bone surfaces in combined arthrodeses. Various fixation methods are in use. Follow-up examination of 52 arthrodeses after 11.1 years revealed good, symptomatic improvement in most patients. However, complete bony union was achieved in only 47 percent, and this was due to insufficient stabilization of the arthrodesis in many cases. In view of comparable rates of pseudarthroses in the literature, we advocate stable internal fixation with screws or bone staples.