The genetic contributions of SNCA and LRRK2 genes to Lewy Body pathology in Alzheimer's disease.

The molecular genetic basis that leads to Lewy Body (LB) pathology in 15-20% of Alzheimer disease cases (LBV/AD) was largely unknown. Alpha-synuclein (SNCA) and Leucine-rich repeat kinase2 (LRRK2) have been implicated in the pathogenesis of Parkinson's disease (PD), the prototype of LB spectrum disorders. We tested the association of SNCA variants with LB pathology in AD. We then stratified the SNCA association analyses by LRRK2 genotype. We also investigated the expression regulation of SNCA and LRRK2 in relation to LB pathology. We evaluated the differences in SNCA-mRNA and LRRK2-mRNA levels as a function of LB pathology in the temporal cortex (TC) from autopsy-confirmed LBV/AD cases and AD controls. We further investigated the cis-effect of the LB pathology-associated genetic variants within the SNCA and LRRK2 loci on the mRNA expression of these genes. SNCA SNPs rs3857059 and rs2583988 showed significant associations with increased risk for LB pathology. When the analyses were stratified by LRRK2-rs1491923 genotype, the associations became stronger for both SNPs and an association was also observed with rs2619363. Expression analysis demonstrated that SNCA- and LRRK2-mRNA levels were significantly higher in TC from LBV/AD brains compared with AD controls. Furthermore, SNCA-mRNA expression level in the TC was associated with rs3857059; homozygotes for the minor allele showed significant higher expression. LRRK2-transcript levels were increased in carriers of rs1491923 minor allele. Our findings demonstrated that SNCA contributes to LB pathology in AD patients, possibly via interaction with LRRK2, and suggested that expression regulation of these genes may be the molecular basis underlying the observed LB associations.

Substantial postoperative pain is common among children undergoing laparoscopic appendectomy.

BACKGROUND: Laparoscopic appendectomy is one of the most common surgical procedures performed in children. However, to our knowledge, the postoperative pain experience of children undergoing laparoscopic appendectomy has never been described. In this study, we assessed the postoperative pain experience of children undergoing laparoscopic appendectomy. METHODS: A retrospective chart review of children aged 9-17 years undergoing laparoscopic appendectomy at a large academic medical center from 2004 to 2010 was performed. Demographic and clinical characteristics and self-reported pain scores (0-10 numeric rating scale) during hospitalization were abstracted from the medical record. Pain scores ≥4 were classified as moderate or severe. If ≥60% of pain ratings were moderate or severe during a specified time period (e.g., particular postoperative day), then the child was defined as experiencing substantial pain during that time. Pain outcomes were summarized using descriptive statistics. Secondary analyses assessed the predictors of substantial postoperative pain. RESULTS: Hundred and eighty-six children underwent laparoscopic appendectomy during the study period. One in three children experienced substantial postoperative pain on the day of surgery, and one in five children continued to have substantial pain the next day. Commonly available clinical and demographic characteristics were poor predictors of substantial postoperative pain. CONCLUSION: These preliminary data suggest that substantial postoperative pain is common in children undergoing laparoscopic appendectomy. More studies of postoperative pain outcomes among children undergoing laparoscopic appendectomy and other common pediatric surgical procedures are needed.

Hyphema in Open-Globe Versus Closed-Globe Injuries in Operation Iraqi Freedom and Enduring Freedom: 2001-2011.

INTRODUCTION: The goal of this study is to update the incidence of hyphema in Operation Iraqi (OIF) and Enduring Freedom (OEF). We wanted to assess associated ocular injuries and final visual acuity (VA) in open-globe versus closed-globe injuries with a hyphema. MATERIALS AND METHODS: We performed a retrospective review of the Walter Reed Ocular Trauma Database (WRTOD) to identify U.S. Service members and DoD civilians with hyphema who were evacuated to Walter Reed Army Medical Center between 2001 and 2011. Primary outcome measures were the final VA and differences in concomitant ocular injuries in open-globe hyphema and closed-globe hyphema. RESULTS: 168 of 890 eyes (18.9%) in the WROTD had a hyphema. Closed-globe injuries were noted in 64 (38.1%) eyes and open-globe injuries in 104 (61.9%) eyes. A final VA of less than 20/200 was noted in 88 eyes (51.8%). Eyes with hyphema were more likely to have traumatic cataract formation (odds ratio (OR) 6.2, 95% confidence interval (CI) 4.2-9.2, P < 0.001), retinal detachment (OR 4.2, CI 2.8-6.4, P < 0.001), angle recession (OR 8.1, CI 2.9-24.3, P < 0.001), and final VA of less than 20/200 (OR 3.7, CI 2.6-5.4, P < 0.001). Traumatic cataract formation (OR 7.4, CI 2.9-18.7, P < 0.001), retinal detachment (OR 6.1, CI 2.1-17.5, P < 0.001), and a final VA less than 20/200 (OR 6.1, CI 2.4-15.4 P < 0.001) were statistically more likely to occur with an open-globe hyphema than with a closed-globe hyphema. CONCLUSIONS: Close follow-up in patients with hyphema is important due to the associated development of traumatic cataract and retinal detachment and poor final visual outcome.

Acute and persistent postoperative pain after breast surgery.

OBJECTIVES: This study's primary aim was to determine levels of acute and persistent postoperative pain and the incidence of severe postoperative pain after mastectomy. A secondary aim was to examine factors associated with postoperative pain. DESIGN: A retrospective cohort study of 196 female breast surgery subjects was conducted. Data were collected on: numerical rating scale (NRS) pain scores in the Post Anesthesia Care Unit (PACU) and at 1 month and 6-12 months postoperative; age; race; insurance; obesity; radiotherapy; chemotherapy; hypertension; anesthesia care time; and intraoperative and PACU opioid use. Severe postoperative pain was defined as NAS > or = 5. Data were analyzed using chi square, Fisher's exact test or analysis of variance, with alpha = 0.05. RESULTS: PACU pain and the incidence of severe PACU pain increased with surgical complexity (P < 0.005). PACU pain scores averaged 4.71 +/- 0.24 and 57.7% of subjects experienced severe pain. Postoperative pain scores at 1 or 6-12 months did not vary by surgical complexity and averaged 2.21 +/- 0.32 and 0.74 +/- 0.22, respectively. Severe postoperative pain was experienced by 22.1% of subjects at 1 month and 8.2% of subjects at 6-12 months. Older age and systolic hypertension were associated with less PACU pain. Non-White race, obesity, and high PACU opioid use were associated with greater postoperative pain at 1 month. Non-White people also had greater postoperative pain at 6-12 months. CONCLUSIONS: The results suggest that nearly 60% of breast surgery patients experience severe acute postoperative pain, with severe pain persisting for 6-12 months in almost 10% of patients.