Growth and differentiation factor-5 (GDF-5) stimulates osteogenic differentiation and increases vascular endothelial growth factor (VEGF) levels in fat-derived stromal cells in vitro

Fat-derived adult mesenchymal stem cells can differentiate into different phenotypes reflecting their potential to regenerate various skeletal tissues. These properties together with the association of adipose with skeletal tissues formed the basis of our study to establish an experimental model for using fat-derived stromal cells to undergo osteogenic differentiation in vitro under the influence of either growth and differentiation factor-5 (GDF-5) or bone morphogenetic protein-2 (BMP-2). Members of the BMP/GDF family of proteins are known for their ability to elicit skeletal morphogenesis, but little is known about the mechanism whereby these morphogens exert their effect on the osteogenic differentiation of fat-derived stromal cells. We compared the effects of GDF-5 and BMP-2 in their recombinant forms to qualitatively and quantitatively determine their influence on the osteogenic differentiation of fat derived stromal cells by examining the effects on mineralization, extracellular matrix, cell proliferation, biochemistry, and gene expression. We identified that GDF-5 not only promotes osteogenic differentiation of rat fat-derived stromal cells, but also may promote angiogenic activity of stromal cells by increasing vascular endothelial growth factor (VEGF) gene expression in vitro. These data suggest that several distinct regulatory mechanisms may exist in association with osteogenic differentiation.     

Posterior Vertebral Column Resection for VATER/VACTERL Associated Spinal Deformity: A Case Report

The VATER/VACTERL association is a syndrome notable for congenital vertebral malformations, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, and renal or limb malformations. Vertebral malformations may include the entire spectrum of congenital spinal deformities, including kyphosis, as was seen in this case. A 14-year-old girl presented to our institution with severe rigid sagittal deformity in the thoracolumbar spine that had recurred following three prior spinal fusion surgeries: the first posterior only, the second anterior and posterior, and the third a posterior only proximal extension. These surgeries were performed to control progressive kyphosis from a complex failure of segmentation that resulted in a 66° kyphosis from T11 to L3 by the time she was 9 years old. Our evaluation revealed solid arthrodesis from the most recent procedures with resultant sagittal imbalance, and surgical options to restore balance included anterior and posterior revision spinal fusion with osteotomies, multiple posterior extension osteotomies with circumferential spine fusion, and posterior vertebral column resection with circumferential spine fusion. She was advised that multiple posterior extension osteotomies would likely be insufficient to restore sagittal balance in the setting of solid arthrodesis from anterior and posterior surgery, and that the posterior-only vertebral column resection would provide results equivalent to revision anterior and posterior surgery, without the morbidity of the anterior approach. She successfully underwent posterior vertebrectomy and circumferential spinal fusion with instrumentation and is doing well 2 years postoperatively. Severe rigid sagittal deformity can be effectively managed with a posterior-only surgical approach, vertebrectomy, and circumferential spinal fusion with instrumentation. An erratum to this article can be found at     

Partially Overlapping Limited Anterior and Posterior Instrumentation for Adult Thoracolumbar and Lumbar Scoliosis: A Description of Novel Spinal Instrumentation, “The Hybrid Technique”

Progressive and/or painful adult spinal deformity in the thoracolumbar and lumbar spine is sometimes treated surgically by long posterior fusions from the thoracic spine down to the pelvis, especially where there is a major thoracic curve component. Recent advances in anterior spinal instrumentation and spinal surgery technique have demonstrated the improved corrective ability offered by anterior stabilization systems, and the added benefit of limiting the number of vertebral fusion levels required for control of the deformity. The "hybrid technique" is a novel use of anterior instrumentation that applies limited anterior instrumentation down to the low lumbar spine (rods and screws), and partially overlapping short-segment posterior instrumentation to the sacrum (pedicle screws and rods). These constructs avoid posterior thoracic instrumentation and fusions, and avoid extension of posterior instrumentation to the pelvis. In the first 10 patients treated using this technique, thoracolumbar and lumbar major curve correction has averaged 71 and 82% in the immediate postoperative period (n = 7), respectively, and 59 and 68% at 2-year follow-up, respectively. The technique is an appealing and attractive alternative for treatment of thoracolumbar and lumbar scoliosis in the adult population, and avoids the requirement for applying spinal fixation to the thoracic spine and the pelvis.     

Endotracheal intubation: the role of sterility

BACKGROUND: There is a paucity of data regarding whether sterile handling of endotracheal tubes (ETTs) impacts the incidence and prevalence of pneumonia in the emergency, urgent, or elective clinical scenarios. Intensive care units employ infection control and reduction schemes to reduce pneumonia rates. METHODS: A MEDLINE search of the English-language literature for the last 30 years was performed using the keywords "endotracheal intubation," "intubation," "pneumonia," "sinusitis," "tracheobronchitis," "nosocomial infection," and "infection." Data were limited to those papers addressing the role of sterile handling or passage of ETTs, infection with antibiotic-resistant micro-organisms, antibiotic prophylaxis, and the role of virulence determinants in supporting invasive infection. Also, a convenience sample of a single author's patients requiring tracheal intubation was undertaken. Data were acquired on tube handling, success of insertion, and subsequent occurrence of pneumonia. RESULTS: Virtually no data exist on the impact of sterile ETT handling, but unsterile manipulation of the ETT prior to insertion is common (112 of 154 intubation events). Within the limited patient sample, no conclusions may be drawn regarding the impact of unsterile handling on pneumonia rates, although sinusitis after nasotracheal intubation clearly increases the incidence of pneumonia. Biofilm generation as a facilitator of bacterial colonization of artificial airway surfaces is a ubiquitous virulence determinant that is not ameliorated by antibiotic administration. CONCLUSIONS: Unsterile ETT handling and insertion techniques are not clearly associated with pneumonia induction, but physiologically sound approaches that retard biofilm production may decrease pneumonia rates.     

Combination of anti-CD4 with anti-LFA-1 and anti-CD154 monoclonal antibodies promotes long-term survival and function of neonatal porcine islet xenografts in spontaneously diabetic NOD mice

Type 1 diabetes mellitus (T1DM) is caused by the autoimmune destruction of pancreatic islet beta-cells, which are required for the production of insulin. Islet transplantation has been shown to be an effective treatment option for TIDM; however, the current shortage of human islet donors limits the application of this treatment to patients with brittle T1DM. Xenotransplantation of pig islets is a potential solution to the shortage of human donor islets provided xenograft rejection is prevented. We demonstrated that a short-term administration of a combination of anti-LFA-1 and anti-CD154 monoclonal antibodies (mAbs) was highly effective in preventing rejection of neonatal porcine islet (NPI) xenografts in non-autoimmune-prone B6 mice. However, the efficacy of this therapy in preventing rejection of NPI xenografts in autoimmune-prone nonobese diabetic (NOD) mice is not known. Given that the current application of islet transplantation is for the treatment of T1DM, we set out to determine whether a combination of anti-LFA-1 and anti-CD154 mAbs could promote long-term survival of NPI xenografts in NOD mice. Short-term administration of a combination of anti-LFA-1 and anti-CD154 mAbs, which we found highly effective in preventing rejection of NPI xenografts in B6 mice, failed to promote long-term survival of NPI xenografts in NOD mice. However, addition of anti-CD4 mAb to short-term treatment of a combination of anti-LFA-1 and anti-CD154 mAbs resulted in xenograft function in 9/12 animals and long-term graft (>100 days) survival in 2/12 mice. Immunohistochemical analysis of islet grafts from these mice identified numerous insulin-producing beta-cells. Moreover, the anti-porcine antibody as well as autoreactive antibody responses in these mice was reduced similar to those observed in naive nontransplanted mice. These data demonstrate that simultaneous targeting of LFA-1, CD154, and CD4 molecules can be effective in inducing long-term islet xenograft survival and function in autoimmune-prone NOD mice.     

Prognostic indicators for upper tract urothelial carcinoma after radical nephroureterectomy: the impact of lymphovascular invasion

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In an array of urological and non‐urological malignancies, lymphovascular invasion (LVI) is a pathological feature known to be associated with adverse outcomes for recurrence and survival. For some cancers, LVI has therefore been incorporated into American Joint Committee on Cancer TNM staging algorithms. This study presents an analysis of the impact of LVI in upper urinary tract urothelial carcinoma (UTUC) treated at our institution over a 20‐year period. In addition to known associations with features of aggressive disease and overall survival, we were able to show that LVI‐positive status upsets the TNM staging for UTUC. Namely, patients with superficial stage and LVI‐positive disease have overall survival outcomes similar to those of patients with muscle‐invasive LVI‐negative carcinoma. Such evidence may support the addition of LVI to future TNM staging algorithms for UTUC.

OBJECTIVE

• ? To assess the impact of lymphovascular invasion (LVI) on the prognosis of patients with upper urinary tract urothelial cell carcinoma (UTUC) treated with radical nephroureterectomy (RNU).

PATIENTS AND METHODS

• ? The Columbia University Medical Center Urologic Oncology database was queried and 211 patients undergoing RNU for UTUC between 1990 and 2010 were identified.
• ? These cases were retrospectively reviewed, and the prognostic significance of relevant clinical and pathological variables was analysed using log‐rank tests and Cox proportional hazards regression models.
• ? Actuarial survival curves were calculated using the Kaplan–Meier method.

RESULTS

• ? LVI was observed in 68 patients (32.2%).
• ? The proportion of LVI increased with advancing stage, high grade, positive margin status, concomitant carcinoma in situ, and lymph node metastases. The 5‐ and 10‐year overall survival rates were 74.7% and 53.1% in the absence of LVI, and 35.7% and 28.6% in the presence of LVI, respectively.
• ? In multivariate analysis, age, race and LVI were independent predictors of overall survival.

CONCLUSIONS

• ? The presence of LVI on pathological review of RNU specimens was associated with worse overall survival in patients with UTUC.
• ? LVI status should be included in the pathological report for RNU specimens to help guide postoperative therapeutic options.
• ? With confirmation from large international studies, inclusion of LVI in the tumour‐node‐metastasis staging system for UTUC should be considered.

     

Surgical treatment of limb-length discrepancy following total hip arthroplasty

BACKGROUND: Although most patients with limb-length discrepancy following total hip arthroplasty have manageable symptoms, others may be disabled as a result of pain or functional impairment. In these patients, reoperation may be indicated to equalize the limb lengths. There is a paucity of published data regarding the outcome of surgical intervention to treat this problem. The purpose of the present study was to evaluate the results of revision hip surgery for the treatment of symptomatic limb-length discrepancy. METHODS: We retrospectively reviewed the clinical and radiographic records of patients who had undergone revision hip surgery at our institution for the treatment of a symptomatic limb-length discrepancy following a previous total hip arthroplasty. We identified twenty-one patients (twenty-one hips) who had an average age of sixty-six years at the time of revision hip arthroplasty. The average duration of follow-up was 2.8 years, and no patient was lost to follow-up. The indications for revision hip arthroplasty were severe hip and/or back pain for eleven patients, instability of the hip for eight, hip pain and ipsilateral limb paresthesia for one, and hip pain and ipsilateral foot drop for one. RESULTS: Revision arthroplasty was performed at a mean of eight months (range, six days to six years) after primary total hip replacement. The mean limb-length discrepancy at the time of the revision was 4 cm (range, 2 to 7 cm). Following revision arthroplasty, which involved revision of a malpositioned acetabular and/or femoral component, equalization of the limb lengths was achieved in fifteen patients. In the remaining six patients, the mean discrepancy had decreased to 1 cm. The mean Harris hip score improved significantly, from 56.5 points before the revision to 83.2 points at the time of the latest follow-up (p < 0.005). All but two patients were satisfied with the outcome of the revision surgery. CONCLUSIONS: Limb-length discrepancy following hip arthroplasty can be associated with pain, paresthesia, and hip instability. In these patients, careful evaluation of the position and orientation of the components may reveal the cause of the discrepancy. Revision arthroplasty may be indicated when a surgically correctable cause of limb-length discrepancy can be identified.     

Reduced duration of intrathecal sufentanil analgesia in laboring cocaine users

On the basis of our previous clinical experience, we hypothesized in this study that the duration and/or quality of labor analgesia produced by intrathecal sufentanil was less in cocaine-abusing parturients compared with nonabusing parturients. Ten micro g of sufentanil was given intrathecally as part of a combined spinal-epidural (CSE) technique to two groups of laboring parturients: 1). those whose urine tested positive for cocaine (cocaine group), and 2). those whose urine tested negative for cocaine (control group). The epidural catheter was not injected with local anesthetic until the patient requested additional pain relief. The time from injection of intrathecal sufentanil until patient request for additional pain relief was defined as duration of analgesia. Baseline visual analog pain score (VAPS) and cervical dilation were measured before the CSE was performed. After injection of intrathecal sufentanil, VAPS was recorded at specific intervals. Cervical dilation was again documented when the patient requested additional analgesia. We found that both groups reported high baseline VAPS and a marked decrease in VAPS after injection of sufentanil that did not differ between groups. Geometric mean duration of pain relief with adjustment for cervical dilation was 87 min in the cocaine group compared with 139 min in the control group (P = 0.019). All patients experienced itching. We conclude that intrathecal sufentanil produces a similar quality but shorter duration of analgesia in cocaine-abusing parturients compared with nonabusing parturients. IMPLICATIONS: Intrathecal sufentanil administered as part of a combined spinal-epidural technique produces similar quality but reduced duration of labor analgesia in cocaine-abusing parturients compared with nonabusing parturients.     

Ten to fifteen-year follow-up after total hip arthroplasty with a tapered cobalt-chromium femoral component (tri-lock) inserted without cement

BACKGROUND: Fixation of the femoral component of a total hip arthroplasty without cement has had variable results. While tapered stems appear to have consistently good results, the duration of follow-up in many series has been relatively short. The purpose of this study was to present a longer-term (ten to fifteen-year) follow-up after total hip arthroplasty with insertion of a tapered femoral component without cement. METHODS: Sixty-seven total hip arthroplasties were performed with insertion of a tapered, cobalt-chromium femoral component without cement in fifty-eight patients from 1983 to 1986. Thirteen patients (fifteen hips) died prior to the fifteen-year follow-up examination, and three patients (three hips) were lost to follow-up after ten years, leaving forty-two patients (forty-nine hips) who were followed clinically for a mean of fifteen years. Thirty-seven of the forty-nine hips were followed radiographically for fifteen years, and the remaining twelve were followed for a minimum of ten years. RESULTS: The mean preoperative Charnley score was 3.0 points for pain, 2.7 points for function, and 3.2 points for motion. At the time of the final follow-up, the mean scores were 5.6, 5.6, and 5.2 points, respectively. Although no preoperative Harris hip scores were available, the mean score at the time of the latest follow-up was 92 points (range, 78 to 100 points). There were no revisions because of isolated aseptic loosening of the femoral component (although revision because of aseptic loosening of the acetabular component led to femoral component revision in seven hips). Two femoral components showed radiographic evidence of instability. At fifteen years, the prevalence of thigh pain was 2%. No femoral component that was thought to be stable, with bone ingrowth at two years, lost fixation. CONCLUSIONS: The design features of this cobalt-chromium femoral component (i.e., the collarless, tapered, wedge fit with circumferential porous coating) are thought to be crucial to the achievement of the good-to-excellent results seen in this study.     

Magnetic Resonance Imaging of Adhesive Capsulitis: Correlation with Clinical Staging

The purpose of this study was to evaluate non-contrast magnetic resonance imaging (MRI) findings of adhesive capsulitis and correlate them with clinical stages of adhesive capsulitis. This will hopefully define a role for shoulder MR imaging in the diagnosis of adhesive capsulitis as well as in potentially directing appropriate treatment. Forty-seven consecutive non-contrast magnetic resonance imaging examinations of 46 patients with a clinical diagnosis of adhesive capsulitis were retrospectively reviewed and correlated with clinical staging. Specific MRI criteria correlated with the clinical stage of adhesive capsulitis, including the thickness and signal intensity of the joint capsule and synovium as well as the presence and severity of scarring in the rotator interval. Routine MRI of the shoulder without intraarticular administration of gadolinium can be used to diagnose all stages of adhesive capsulitis, including stage 1, where findings may be subtle on clinical examination. We believe that future studies assessing the role of MRI in guiding the initiation of appropriate treatment should be undertaken.