Citations

Abstract The MHC in humans encodes the most polymorphic genes, the HLA genes, which are critical for the immune system to clear infection. This can be attributed to strong selection pressure as populations moved to different parts of the world and encountered new kinds of infections, leading to new HLA class II alleles. HLA genes also have the highest relative risk for autoimmune diseases. Three haplotypes, that is, HLA-DR2DQ6, DR4DQ8, and DR3DQ2, account for HLA association with most autoimmune diseases. We hypothesize that these haplotypes, along with their multiple subtypes, have survived bottlenecks of infectious episodes in human history because of their ability to present pathogenic peptides to activate T cells that secrete cytokines to clear infections. Unfortunately, they also present self-peptides/mimics to activate autoreactive T cells secreting proinflammatory cytokines that cause autoimmune diseases.

Abstract Background: The Food and Drug Administration issued a black box warning regarding the use of droperidol and the potential for torsade de pointes. Methods: The primary objective of this retrospective study was to determine if low-dose (0.625 mg) droperidol administration was associated with episodes of torsade de pointes in the general surgical population during the 3-yr period following the reinstitution of droperidol to our institutional formulary. Results: The authors identified 20,122 surgical patients who received 35,536 doses of droperidol. These patients were cross-matched with an electrocardiogram database and an adverse outcome database. The charts of 858 patients were reviewed, including patients with documentation of prolonged QTc (>440 ms) from March 2007 to February 2011, polymorphic ventricular tachycardia (VT) within 48 h of receiving droperidol, or death within 7 days of receiving droperidol. Twelve surgical patients had VT (n = 4) or death (n = 8) documented within 48 h of droperidol administration. No patients developed polymorphic VT or death due to droperidol administration (n = 0). The eight patients that died were on palliative care. The four patients with documented VT had previous cardiac conditions: two had pre-existing implantable cardiac defibrillators, three had episodes of VT before receiving droperidol, and another had pre-existing hypertrophic obstructive cardiomyopathy. The authors found 523 patients with a documented QTc >440 ms before receiving droperidol. No patients developed VT or death as a direct result of droperidol administration. Conclusions: Our evidence suggests that low-dose droperidol does not increase the incidence of polymorphic VT or death when used to treat postoperative nausea and vomiting in the surgical population.

Background and Purpose— The best management of patients with unruptured brain arteriovenous malformations (BAVM) is controversial. In this study, we analyzed the stroke rate and functional outcomes of patients having stereotactic radiosurgery (SRS) for unruptured BAVM using the same eligibility criteria and primary end points as the ARUBA trial. Methods— Retrospective observational study of 174 ARUBA-eligible patients having SRS from 1990 to 2005. Results— The median follow-up after SRS was 64 months. Fifteen patients (8.7%) had a hemorrhagic stroke at a median of 21 months after SRS. Six patients (3.5%) had a focal neurological deficit and 4 patients died (2.3%). The risk of stroke or death was 10.3% at 5 years and 11.5% at 10 years. Twelve additional patients (6.9%) had a focal neurological deficit from either radiation-related complications (n=7) or subsequent resection (n=5). The risk of patients’ having clinical impairment (modified Rankin Score ≥2) was 8.4% at 5 years and 12.0% at 10 years. Increasing BAVM volume was associated with both stroke or death (hazard ratio=1.06; 95% confidence interval, 1.0–1.11; P =0.04) and clinical impairment (hazard ratio=1.06; 95% confidence interval, 1.01–1.09; P =0.01). The 10-year risk of stroke or death and clinical impairment for patients with BAVM ≤5.6 cm 3 was 5% and 4%, respectively. Conclusions— The observed risk of stroke or death after SRS was approximately 2% per year for the first 5 years after SRS, declining to 0.2% annually for years 6 to 10. Patients with small volume BAVM may benefit from SRS compared with the natural history of unruptured BAVM over the planned follow-up interval of the ARUBA trial (5–10 years).

Background Patient-reported signs and symptoms are often the first indication of clinically relevant lymphedema. Objective The purpose of this study was to develop and assess the diagnostic accuracy of a screening questionnaire to detect lower-extremity lymphedema (LEL) among normal-weight women and women with obesity. Design This was a cross-sectional survey study. Methods The authors reviewed existing questionnaires assessing upper-extremity lymphedema (UEL) for potential questions and worked with content experts to generate new items. A draft questionnaire with 59 items was reviewed by 5 physicians and 5 physical therapists who specialized in lymphedema management and 5 female patients with clinically confirmed secondary LEL. A revised questionnaire with 45 items was administered by mail to 186 women with clinically confirmed LEL (n=116) or UEL (n=70). A total of 99 women (53.2% of 186) completed the mailed survey, and 28 women with lymphedema who were recruited directly in a lymphedema clinic waiting area also completed the survey. A parsimonious subset of items that best discriminated patients with and without LEL was identified using chi-square tests and logistic regression. Sensitivity and specificity for detecting LEL and positive and negative likelihood ratios (LR+, LR−) were estimated for the entire sample and for subsamples defined by obesity (body mass index ≥30 versus <30 kg/m2), which may confound the accurate diagnosis of LEL. Results Questionnaires were completed by 127 women (LEL group, n=88; UEL group, n=39). A sum of 13 items (score range=0–52) was the most discriminating. Using a cutoff score of ≥5 points, the sensitivity and specificity for detecting LEL among all participants were 95.5% and 86.5%, respectively (LR+=7.1, LR−=0.05), and 94.8% and 76.5%, respectively (LR+=4.0, LR−=0.07), for participants who were obese. Limitations By enumerating a sample with a high prevalence of LEL, a spectrum bias may have been introduced, which may have affected the accuracy of the screening questionnaire. Conclusions The brief, 13-item self-report questionnaire is a sensitive and specific tool for detecting clinically relevant LEL among women, including those with a body mass index of ≥30 kg/m2.