Topical corticosteroids in psoriasis: strategies for improving safety

Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long‐term use of these agents.     

Quantification of CD4+ T Cell Alloreactivity and Its Control by Regulatory T Cells Using Time‐Lapse Microscopy and Immune Synapse Detection

Assays designed to select transplant recipients for immunosuppression withdrawal have met with limited success, perhaps because they measure events downstream of T cell–alloantigen interactions. Using in vitro time‐lapse microscopy in a mouse transplant model, we investigated whether transplant outcome would result in changes in the proportion of CD4⁺ T cells forming prolonged interactions with donor dendritic cells. By blocking CD4–MHC class II and CD28–B7 interactions, we defined immunologically relevant interactions as those ≥500 s. Using this threshold, T cell–dendritic cell (T‐DC) interactions were examined in rejection, tolerance and T cell control mediated by regulatory T cells. The frequency of T‐DC contacts ≥500 s increased with T cells from mice during acute rejection and decreased with T cells from mice rendered unresponsive to alloantigen. Regulatory T cells reduced prolonged T‐DC contacts. Importantly, this effect was replicated with human polyclonally expanded naturally occurring regulatory T cells, which we have previously shown can control rejection of human tissues in humanized mouse models. Finally, in a proof‐of‐concept translational context, we were able to visualize differential allogeneic immune synapse formation in polyclonal CD4⁺ T cells using high‐throughput imaging flow cytometry.     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients

High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.     

High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.     

Pulmonary arteriovenous malformations: techniques and long-term outcome of embolotherapy

Over a 10-year period, 276 pulmonary arteriovenous malformations (PAVMs) were occluded with balloon embolotherapy in 76 patients, 67 (88%) of whom had hereditary hemorrhagic telangiectasia. Eleven patients (14%) were discovered by means of family screening with measurement of arterial blood gases and chest radiography. Epistaxis, dyspnea, hemoptysis, and hemothorax occurred in 79%, 71%, 13%, and 9% of patients, respectively. Clinical histories of strokes and transient ischemic attacks were present in 18% and 37% of patients, respectively. Computed tomographic scans of 59 patients showed stroke in 36%. Sixty-five percent of PAVMs were located in the lower lobes, which correlated with the finding of more pronounced hypoxemia in the upright position. After embolotherapy, symptomatic hypoxemia was corrected, and serial values have remained constant for 5 years. Complications were minimal, and no patient required surgery. Balloon embolotherapy is effective long-term therapy for PAVMs, and family screening should be pursued because of the possibility of a higher frequency of paradoxical embolization (stroke) than previously recognized.     

What Are the Interobserver and Intraobserver Variability of Gap and Stepoff Measurements in Acetabular Fractures?

BackgroundGap and stepoff values in the treatment of acetabular fractures are correlated with clinical outcomes. However, the interobserver and intraobserver variability of gap and stepoff measurements for all imaging modalities in the preoperative, intraoperative, and postoperative phase of treatment is unknown. Recently, a standardized CT-based measurement method was introduced, which provided the opportunity to assess the level of variability.Questions/purposes(1) In patients with acetabular fractures, what is the interobserver variability in the measurement of the fracture gaps and articular stepoffs determined by each observer to be the maximum one in the weightbearing dome, as measured on pre- and postoperative pelvic radiographs, intraoperative fluoroscopy, and pre- and postoperative CT scans? (2) What is the intraobserver variability in these measurements?MethodsSixty patients with a complete subset of pre-, intra- and postoperative high-quality images (CT slices of < 2 mm), representing a variety of fracture types with small and large gaps and/or stepoffs, were included. A total of 196 patients with nonoperative treatment (n = 117), inadequate available imaging (n = 60), skeletal immaturity (n = 16), bilateral fractures (n = 2) or a primary THA (n = 1) were excluded. The maximum gap and stepoff values in the weightbearing dome were digitally measured on pelvic radiographs and CT images by five independent observers. Observers were free to decide which gap and/or stepoff they considered the maximum and then measure these before and after surgery. The observers were two trauma surgeons with more than 5 years of experience in pelvic surgery, two trauma surgeons with less than 5 years of experience in pelvic surgery, and one surgical resident. Additionally, the final intraoperative fluoroscopy images were assessed for the presence of a gap or stepoff in the weightbearing dome. All observers used the same standardized measurement technique and each observer measured the first five patients together with the responsible researcher. For 10 randomly selected patients, all measurements were repeated by all observers, at least 2 weeks after the initial measurements. The intraclass correlation coefficient (ICC) for pelvic radiographs and CT images and the kappa value for intraoperative fluoroscopy measurements were calculated to determine the inter- and intraobserver variability. Interobserver variability was defined as the difference in the measurements between observers. Intraobserver variability was defined as the difference in repeated measurements by the same observer.ResultsPreoperatively, the interobserver ICC was 0.4 (gap and stepoff) on radiographs and 0.4 (gap) and 0.3 (stepoff) on CT images. The observers agreed on the indication for surgery in 40% (gap) and 30% (stepoff) on pelvic radiographs. For CT scans the observers agreed in 95% (gap) and 70% (stepoff) of images. Postoperatively, the interobserver ICC was 0.4 (gap) and 0.2 (stepoff) on radiographs. The observers agreed on whether the reduction was acceptable or not in 60% (gap) and 40% (stepoff). On CT images the ICC was 0.3 (gap) and 0.4 (stepoff). The observers agreed on whether the reduction was acceptable in 35% (gap) and 38% (stepoff). The preoperative intraobserver ICC was 0.6 (gap and stepoff) on pelvic radiographs and 0.4 (gap) and 0.6 (stepoff) for CT scans. Postoperatively, the intraobserver ICC was 0.7 (gap) and 0.1 (stepoff) on pelvic radiographs. On CT the intraobserver ICC was 0.5 (gap) and 0.3 (stepoff). There was no agreement between the observers on the presence of a gap or stepoff on intraoperative fluoroscopy images (kappa -0.1 to 0.2).ConclusionsWe found an insufficient interobserver and intraobserver agreement on measuring gaps and stepoffs for supporting clinical decisions in acetabular fracture surgery. If observers cannot agree on the size of the gap and stepoff, it will be challenging to decide when to perform surgery and study the results of acetabular fracture surgery.Level of EvidenceLevel III, diagnostic study.     

Delayed occurrence of multiple spinal drop metastases from a posterior fossa choroid plexus papilloma. Case report

Choroid plexus papilloma is a benign central nervous system tumor that occasionally spreads along the subarachnoid space. The authors report the case of a 49-year-old man who presented with back pain 19 years after resection of a posterior fossa choroid plexus papilloma. Magnetic resonance imaging revealed multiple spinal lesions without any residual or recurrent intracranial tumor. All spinal lesions were resected and histologically diagnosed as atypical choroid plexus papilloma. The authors suggest that patients in whom choroid plexus papilloma is diagnosed should undergo total neuraxis imaging at the time of initial diagnosis as well as periodic follow-up examinations after resection to rule out drop metastases.