André Kaelin

Kingella Kingae osteoarticular infections in young children: clinical features and contribution of a new specific real-time PCR assay to the diagnosis

Backgroung Kingella kingae is an emerging pathogen that may be recognized as the most common bacteria responsible for osteoarticular infections (OAI) in young children. However, its diagnosis remains a challenge and thus little evoked in infants, because K. kingae is a difficult germ to isolate on solid medium, and clinical signs are often mild. The main objective of this prospective study is to describe the clinical, biologic, and radiologic features of children with OAI caused by K. kingae. In addition, we describe the usage of a new specific real-time PCR assay in children under 4 years admitted for OAI with a probe that detects 2 independent gene targets from the K. kingae RTX toxin. Patients and Methods All children less than 4 years admitted in our institution between January 2007 and November 2009 for suspected OAI were enrolled in this prospective study (43 cases). Age, gender, clinical signs, duration of symptoms, bone or joint involved, imaging studies, and laboratory data, including bacterial investigations, full blood count, erythrocyte sedimentation rate, and serum C-reactive protein were collected for analysis. Results Identification of the microorganism was possible for 28 cases (65.1%) yielding K. kingae in 23 cases (82.1%). Mean age of children with K. kingae OAI was 19.6 months. Less than 15% of these patients were febrile during the admission, but 46% of them presented a history of fever-peak superior to 38.5°C before admission. Thirty-nine percent of the children with K. kingae OAI had normal C-reactive protein; WBC was elevated in only 2 cases, whereas 21 patients had abnormal erythrocyte sedimentation rate, and 13 abnormal platelet counts. Direct Gram staining and classical isolation methods were negative for all cases subsequently detected as K. kingae OAI by specific real-time PCR. Conclusion This study confirms that K. kingae is the major bacterial cause of OAI in children less than 4 years. The real-time PCR assay, specific to the K. kingae RTX toxin, provides interesting diagnostic performance when implemented in the routine microbiologic laboratory. Needless to say, a bigger cohort is required to adequately study this new qPCR assay, but the results so far seem promising. The most important additional finding is the mild-to-moderate clinical, radiologic, and biologic inflammatory response to K. kingae infection with the result that these children present few criteria evocative of OAI. Level of Evidence II

Fibrogenic potential of human multipotent mesenchymal stromal cells in injured liver.

Multipotent mesenchymal stromal cells (MSC) are currently investigated clinically as cellular therapy for a variety of diseases. Differentiation of MSC toward endodermal lineages, including hepatocytes and their therapeutic effect on fibrosis has been described but remains controversial. Recent evidence attributed a fibrotic potential to MSC. As differentiation potential might be dependent of donor age, we studied MSC derived from adult and pediatric human bone marrow and their potential to differentiate into hepatocytes or myofibroblasts in vitro and in vivo. Following characterization, expanded adult and pediatric MSC were co-cultured with a human hepatoma cell line, Huh-7, in a hepatogenic differentiation medium containing Hepatocyte growth factor, Fibroblast growth factor 4 and oncostatin M. In vivo, MSC were transplanted into spleen or liver of NOD/SCID mice undergoing partial hepatectomy and retrorsine treatment. Expression of mesenchymal and hepatic markers was analyzed by RT-PCR, Western blot and immunohistochemistry. In vitro, adult and pediatric MSC expressed characteristic surface antigens of MSC. Expansion capacity of pediatric MSC was significantly higher when compared to adult MSC. In co-culture with Huh-7 cells in hepatogenic differentiation medium, albumin expression was more frequently detected in pediatric MSC (5/8 experiments) when compared to adult MSC (2/10 experiments). However, in such condition pediatric MSC expressed alpha smooth muscle more strongly than adult MSC. Stable engraftment in the liver was not achieved after intrasplenic injection of pediatric or adult MSC. After intrahepatic injection, MSC permanently remained in liver tissue, kept a mesenchymal morphology and expressed vimentin and alpha smooth muscle actin, but no hepatic markers. Further, MSC localization merges with collagen deposition in transplanted liver and no difference was observed using adult or pediatric MSC. In conclusion, when transplanted into an injured or regenerating liver, MSC differentiated into myofibroblasts with development of fibrous tissue, regardless of donor age. These results indicate that MSC in certain circumstances might be harmful due to their fibrogenic potential and this should be considered before potential use of MSC for cell therapy.

Synovial sarcomas usually metastasize after >5 years: a multicenter retrospective analysis with minimum follow-up of 10 years for survivors

BACKGROUND Synovial sarcoma (SS) is a malignant soft tissue sarcoma with a poor prognosis because of late local recurrence and distant metastases. To our knowledge, no studies have minimum follow-up of 10 years that evaluate long-term outcomes for survivors. PATIENTS AND METHODS Data on 62 patients who had been treated for SS from 1968 to 1999 were studied retrospectively in a multicenter study. Mean follow-up of living patients was 17.2 years and of dead patients 7.7 years. RESULTS Mean age at diagnosis was 35.4 years (range 6-82 years). Overall survival was 38.7%. The 5-year survival was 74.2%; 10-year survival was 61.2%; and 15-year survival was 46.5%. Fifteen patients (24%) died of disease after 10 years of follow-up. Local recurrence occurred after a mean of 3.6 years (range 0.5-14.9 years) and metastases at a mean of 5.7 years (range 0.5-16.3 years). Only four patients were treated technically correctly with a planned biopsy followed by a wide resection or amputation. Factors associated with significantly worse prognosis included larger tumor size, metastases at the time of diagnosis, high-grade histology, trunk-related disease, and lack of wide resection as primary surgical treatment. CONCLUSIONS In SS, metastases develop late with high mortality. Patients with SS should be followed for >10 years.

Differentiating Osteoarticular Infections Caused By kingella Kingae From Those Due to Typical Pathogens in Young Children

Osteoarticular infections caused by Kingella kingae are characterized by mild-to-moderate clinical and biologic inflammatory signs that are different from those caused by Gram-positive cocci. A combined score was built to find the best model to predict K. kingae osteoarticular infections by using the following 4 variables: body temperature <38°C, serum C-reactive protein <55 mg/L, white blood cell count <14,000/mm3, and band forms <150/mm3.

One hundred pediatric femoral fractures: epidemiology, treatment attitudes, and early complications

Analysis of 100 consecutive femoral fractures admitted to our institution revealed an incidence of about 1 fracture per 2,000 children per year. Epidemiologic data may help to promote prevention. Initial treatment was performed by many doctors, thus rendering guidelines to safe and cost-effective management indispensable. In the last decade, growing concern to reduce hospital stays and costs led to new approaches that replaced traction as a therapeutic principle. Today. we consider immediate spica casting a good option for the group 0–5 years old, whereas in the age group 5–12 years old elastic stable intramedullary nailing (ESIN) produces reliably good results. Minor complications were common and could be avoided partially, but they did not affect the good final outcome.

Effects of Cast-Mediated Immobilization on Bone Mineral Mass at Various Sites in Adolescents with Lower-Extremity Fracture

BACKGROUND Leg or ankle fractures occur commonly in the pediatric population and are primarily treated with closed reduction and cast immobilization. The most predictable consequences of immobilization and subsequent weight-bearing restriction are loss of bone mineral mass, substantial muscle atrophy, and functional limitations. The purposes of this study were to determine if lower-limb fractures in adolescents are associated with abnormal bone mineral density or content at the time of fracture, and to quantify bone mineral loss at various sites due to cast-mediated immobilization and limited weight-bearing. METHODS We recruited fifty adolescents aged ten to sixteen years who had undergone cast immobilization for a leg or ankle fracture. Dual x-ray absorptiometry scans of the total body, lumbar spine, hip, leg, and calcaneus were performed at the time of fracture and at cast removal. Patients with a fracture were paired with healthy controls according to sex and age. Values at baseline and at cast removal, or at equivalent time intervals in the control group, were compared between groups and between the injured and uninjured legs of the adolescents with the fracture. RESULTS At the time of fracture, there were no observed differences in the bone mineral density or bone mineral content Z-scores of the total body or the lumbar spine, or in the bone mineral density Z-scores of the calcaneus, between the injured and healthy subjects. At cast removal, bone mineral parameters on the injured side were significantly lower than those on the uninjured side in the injured group. Differences ranged from -5.8% to -31.7% for bone mineral density and from -5.2% to -19.4% for bone mineral content. During the cast period, the injured adolescents had a significant decrease of bone mineral density at the hip, greater trochanter, calcaneus, and total lower limb as compared with the healthy controls. CONCLUSIONS Lower-limb fractures are not related to osteopenia in adolescents at the time of fracture. However, osteopenia does develop in the injured limb during cast immobilization for fracture treatment. Further investigation is required to determine if the bone mineral mass will return to normal or if a permanent decrease is to be expected, which may constitute a hypothetical risk of sustaining a second fracture.

Safety and efficacy of patient controlled epidural analgesia following pediatric spinal surgery

Background:  Patient controlled epidural analgesia (PCEA) is uncommon in pediatric anesthesia. Because PCEA offers superior pain control compared with continuous epidural infusions in adults, we prospectively evaluated the analgesia efficacy and safety of PCEA in children and adolescents following extensive spinal surgery.

Low Protein Intake Is Associated With Impaired Titanium Implant Osseointegration

Low protein intake is highly prevalent among orthopaedic elderly patients. We studied the effects of an isocaloric low protein diet on the resistance to pull‐out of titanium rods implanted into rats proximal tibia. Isocaloric low protein intake impairs titanium implant osseointegration, with a decreased strength needed to completely loose the implant and altered bone microarchitecture in its vicinity.

Cuboid nutcracker fracture due to horseback riding in children: case series and review of the literature.

We report 4 cases of nutcracker fractures of the cuboid resulting from equestrian sport in pediatric population. These lesions are often consistent with a trauma in forced abduction of the forefoot. The particular mechanism of the cuboid fracture due to horseback riding in children is discussed. The methods used to radiographically evaluate the compression fracture of the cuboid and its associated injuries are presented. Left untreated, these fractures can lead to severe alterations in foot mechanics and function, such as to severe pain. In addition, the surgical treatment to correct the nutcracker fracture of the cuboid in our patients is presented.

Gorham‐stout disease of costo‐vertebral localization: radiographic, scintigraphic, computed tomography, and magnetic resonance imaging findings

Gorham‐Stout disease is a clinical, radiographic, and histological entity characterized by progressive osteolysis as a result of a histologically benign vascular proliferation involving bone. We present a case involving the cervical and thoracic spine and the osseous thorax, with attention to the clinical, radiographic, scintigraphic, computed tomography, and magnetic resonance imaging findings. These subjects are discussed in the light of the literature.