Citations

Background Perioperative nerve injury (PNI) is one of the most debilitating complications after total knee arthroplasty (TKA). Although regional anesthesia (RA) techniques reduce pain and improve functional outcomes after TKA, they may also contribute to PNI. The objective of this study was to test the hypothesis that PNI risk differs among patients according to RA use during TKA. Methods All patients aged at least 18 yr who underwent elective TKA from January 1988 to July 2007 were retrospectively identified. The primary outcome variable was the presence of a new PNI documented within 3 months of the procedural date. Age, sex, body mass index, type of procedure, tourniquet time, type of anesthesia, and use of peripheral nerve blockade were evaluated as potential risk factors for PNI using multivariable logistic regression. Results Ninety-seven cases of PNI were identified among 12,329 patients. Overall incidence of PNI was 0.79% (95% CI, 0.64-0.96%). PNI was not associated with peripheral nerve blockade (odds ratio [OR], 0.97) or type of anesthesia (OR, 1.10 [neuraxial vs. general]; OR, 1.82 [combined vs. general]). Risk for PNI decreased with age (OR, 0.68 [per decade]; P < 0.001) but increased with tourniquet time (OR, 1.28 [per 30-min increase]; P = 0.003) and bilateral procedures (OR, 2.51; P < 0.001). Patients with PNI who underwent peripheral nerve blockade were less likely to have complete neurologic recovery (OR, 0.37; P = 0.03). Conclusions Risk for PNI after TKA was unchanged by the use of RA techniques. This finding supports the notion that the known benefits of RA for patients undergoing TKA can be achieved without increasing risk of neurologic injury. However, in rare situations when PNI occurs, complete recovery may be less likely if it develops after peripheral nerve blockade.

Patients with cancer often have complex needs that must be met within a short intervention window. The authors highlight opportunities for improved multidisciplinary care for patients with advanced cancer and their families.

Genome-wide association studies have identified an association between two intronic single nucleotide polymorphisms (SNPs), rs12722489 and rs2104286, in the interleukin-2 receptor alpha-chain gene ( IL2RA) and susceptibility to multiple sclerosis (MS). We studied these SNPs in association with susceptibility to and severity of MS in a population-based cohort of 220 patients from Olmsted County, Minnesota, compared with 442 matched controls. We sequenced the exons, splice sites and 5’ and 3’ untranslated regions in 27 randomly selected MS patients (powered for allele frequency ≥0.04) to search for mutations. No novel missense mutation was identified. Two patients (7.5%) had an exon 2 SNP ( rs4308625) and two patients had an exon 4 SNP ( rs2228149), both synonymous.

ABSTRACT Introduction Erectile dysfunction (ED) may be the most commonly observed adverse event (AE) associated with the combination of radiation therapy (RT) and androgen deprivation therapy (ADT). A significant number of men are trying phosphodiesterase type 5 inhibitors (PDE5s) such as sildenafil to treat ED, yet sildenafil studies to date shed little light on the response to ED after ADT. Aim The purpose of this trial was to evaluate sildenafil in the treatment of ED in prostate cancer patients previously treated with external beam RT and neoadjuvant and concurrent ADT. Methods In this randomized, double-blinded crossover trial, eligible patients received RT/ADT for intermediate risk prostate cancer and currently had ED as defined by the International Index of Erectile Function (IIEF). Patients were randomized to 12 weeks of sildenafil or placebo followed by 1 week of no treatment then 12 weeks of the alternative. Treatment differences were evaluated using a marginal model for binary crossover data. Main Outcome Measures The primary end point was improved erectile function, as measured by the IIEF. Results The study accrued 115 patients and 61 (55%) completed all three IIEF assessments. Sildenafil effect was significant (P = 0.009) with a difference in probabilities of erectile response of 0.17 (95% confidence interval: 0.06, 0.29), and 0.21 (0.06, 0.38) for patients receiving ≤120 days of ADT. However, as few as 21% of patients had a treatment-specific response, only improving during sildenafil but not during the placebo phase. Conclusions This is the first controlled trial to suggest a positive sildenafil response for ED treatment in patients previously treated with RT/ADT, however, only a minority of patients responded to treatment. ADT duration may be associated with response and requires further study. The overall low response rate suggests the need for study of additional or preventative strategies for ED after RT/ADT for prostate cancer.

Object Supratentorial cortical ependymomas (CE) are rare, with 7 cases reported. The lesions, typically occurring in the superficial cortex in young adults and associated with a history of seizures, are not fully characterized. Furthermore, their relationship with the recently described angiocentric glioma (AG) is still being debated. This study was undertaken to summarize the authors' experience with CEs. Methods Between 1997 and 2009, 202 cases of ependymoma were surgically treated at the Mayo Clinic, 49 of which were supratentorial. Among these, 9 CE cases were retrospectively identified. Clinical, imaging, and pathological features of each case were reviewed. Results Tumors arose from the frontal (5 cases), parietal (3), and occipital (1) lobes. No tumor occurred in the temporal lobe, despite its reported association with seizures. The mean age at presentation was 27 ± 19 years (± SD) and age at resection was 36 ± 16 years. The mean size of the lesion was 16 ± 14 cm3. Seizures were the presenting symptom in 78%. Cross-sectional imaging in 8 cases was characterized by a heterogeneous mass with multiple cystlike areas and enhancement of the soft-tissue component. Gross-total resection was achieved in 8 of 9 tumors. Pathologically, 6 were low-grade (WHO Grade II) and 3 were anaplastic (WHO Grade III) ependymomas. All tumors exhibited the focal presence of perivascular pseudorosettes, but only 1 (11%) exhibited the focal presence of a true rosette. A bipolar spindle cell component resembling AG was present in 3 (33%) and “Schwannian-like” nodules in 2 (22%). Subpial aggregation and peripheral infiltration were present in 4 cases (44%). With a mean postsurgery follow-up of 62 ± 38 months, only 2 lesions recurred locally after imaging-confirmed gross-total resection, both being Grade III. In 5 (71%) of 7 patients presenting with seizures an Engel Class I outcome was achieved. Conclusions Cortical ependymomas represent a rare type of ependymoma occurring superficially in the cortex. Morphologically, these tumors are protean, varying from classic to epithelioid, clear cell, and tanycytic. Some also exhibited features typical of AG. Most tumors were low grade and cured with resection. Anaplastic tumors occur and may recur locally despite provision of radiation therapy. Cortical ependymomas frequently, but not always, present with seizures, but despite their high association with epilepsy, none occurred in the temporal lobe in any of the authors' 9 patients. Overall, CEs appear to have a relatively favorable prognosis compared with other supratentorial ependymomas.

Purpose TO describe a case of exudative macular detachment secondary to peripheral exudative chorioretinopathy with a favorable anatomic and visual outcome following treatment with intravitreal bevacizumab. Methods The medical records of a patient with peripheral exudative chorioretinopathy were reviewed. Results Macular reattachment was achieved with a corresponding visual acuity improvement that was maintained over an uncomplicated 17-month clinical course. Conclusions Bevacizumab may be an effective treatment option for exudative macular detachment secondary to peripheral exudative hemorrhagic chorioretinopathy.

AbstractGenome‐wide association studies (GWAS) are being conducted at an unprecedented rate in population‐based cohorts and have increased our understanding of the pathophysiology of complex disease. Regardless of context, the practical utility of this information will ultimately depend upon the quality of the original data. Quality control (QC) procedures for GWAS are computationally intensive, operationally challenging, and constantly evolving. Here we enumerate some of the challenges in QC of GWAS data and describe the approaches that the electronic MEdical Records and Genomics (eMERGE) network is using for quality assurance in GWAS data, thereby minimizing potential bias and error in GWAS results. We discuss common issues associated with QC of GWAS data, including data file formats, software packages for data manipulation and analysis, sex chromosome anomalies, sample identity, sample relatedness, population substructure, batch effects, and marker quality. We propose best practices and discuss areas of ongoing and future research. Curr. Protoc. Hum. Genet. 68:1.19.1‐1.19.18 © 2011 by John Wiley & Sons, Inc.

Abstract The CD3ε cytoplasmic tail contains a conserved proline-rich sequence (PRS) that influences TCR–CD3 expression and signaling. Although the PRS can bind the SH3.1 domain of the cytosolic adapter Nck, whether the PRS is constitutively available for Nck binding or instead represents a cryptic motif that is exposed via conformational change upon TCR–CD3 engagement (CD3Δc) is currently unresolved. Furthermore, the extent to which a cis-acting CD3ε basic amino acid-rich stretch (BRS), with its unique phosphoinositide-binding capability, might impact PRS accessibility is not clear. In this study, we found that freshly harvested primary thymocytes expressed low to moderate basal levels of Nck-accessible PRS (“open-CD3”), although most TCR–CD3 complexes were inaccessible to Nck (“closed-CD3”). Ag presentation in vivo induced open-CD3, accounting for half of the basal level found in thymocytes from MHC+ mice. Additional stimulation with either anti-CD3 Abs or peptide–MHC ligands further elevated open-CD3 above basal levels, consistent with a model wherein antigenic engagement induces maximum PRS exposure. We also found that the open-CD3 conformation induced by APCs outlasted the time of ligand occupancy, marking receptors that had been engaged. Finally, CD3ε BRS–phosphoinositide interactions played no role in either adoption of the initial closed-CD3 conformation or induction of open-CD3 by Ab stimulation. Thus, a basal level of open-CD3 is succeeded by a higher, induced level upon TCR–CD3 engagement, involving CD3Δc and prolonged accessibility of the CD3ε PRS to Nck.