Intra-Arterial Thrombolysis for Acute Central Retinal Artery Occlusion: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Acute central retinal artery occlusion (CRAO) is a serious ophthalmologic emergency that may result in monocular blindness. To date, studies evaluating intra-arterial thrombolysis (IAT) have not shown a definitive clinical benefit. We have conducted a systematic review with a meta-analysis to effectively evaluate this treatment option. METHODS: A systematic literature search was focused on studies containing five or more patients undergoing IAT that included a control group treated with standard therapy. Pooled meta-analysis was performed. RESULTS: Five retrospective controlled studies and one randomized clinical trial were identified satisfying all inclusion criteria resulting in the analysis of 236 patients treated with IAT and 255 patients treated with ST. A pooled fixed effects analysis resulted in an estimated odds ratio of 2.52, 95% CI (1.69, 3.77) (P < 0.0001) favoring IAT. CONCLUSION: IAT is a promising therapeutic option for CRAO with great potential. Further randomized trials are needed to establish a significant benefit and ensure the safety of the intervention.

Unique Genes in Tumor-Positive Sentinel Lymph Nodes Associated with Nonsentinel Lymph Node Metastases in Melanoma.

BACKGROUND: Current risk assessment tools to estimate the risk of nonsentinel lymph node metastases after completion lymphadenectomy for a positive sentinel lymph node (SLN) biopsy in cutaneous melanoma are based on clinical and pathologic factors. We identified a novel genetic signature that can predict non-SLN metastases in patients with cutaneous melanoma staged with a SLN biopsy. METHODS: RNA was collected for tumor-positive SLNs in patients staged by SLN biopsy for cutaneous melanoma. All patients with a tumor-positive SLN biopsy underwent completion lymphadenectomy. A 1:10 case:control series of positive and negative non-SLN patients was analyzed by microarray and quantitative RT-PCR. Candidate differentially expressed genes were validated in a 1:3 case:control separate cohort of positive and negative non-SLN patients. RESULTS: The 1:10 case:control discovery set consisted of 7 positive non-SLN cases matched to 70 negative non-SLN controls. The cases and controls were similar with regards to important clinicopathologic factors, such as gender, primary tumor site, age, ulceration, and thickness. Microarray and RT-PCR identified six potential differentially expressed genes for validation. In the 40-patient separate validation set, 10 positive non-SLN patients were matched to 30 negative non-SLN controls based on gender, ulceration, age, and thickness. Five of the six genes were differentially expressed. The five gene panel identified patients at low (7.1%) and high risk (66.7%) for non-SLN metastases. CONCLUSIONS: A novel, non-SLN gene score based on differential expressed genes in a tumor-positive SLN can identify patients at high and low risk for non-SLN metastases.

Visual Improvement after Intra-Arterial Thrombolysis for Central Retinal Artery Occlusion Does Not Correlate with Time to Treatment.

BACKGROUND: Intra-arterial thrombolysis (IAT) for the treatment of acute central retinal artery occlusion (CRAO) has demonstrated variable results for improving visual acuity and remains controversial. Despite limited evidence, time from symptom onset to thrombolysis is believed to be an important factor in predicting visual improvement after IAT. METHODS: A comprehensive review of the literature was conducted and individual subject level data were extracted from relevant studies. From these, a secondary analysis was performed. Initial and final logarithm of the minimum angle of resolution (logMAR) scores were either abstracted directly from relevant studies or converted from provided Snellen chart scores. Change in logMAR scores was used to determine overall treatment efficacy. RESULTS: Data on 118 patients undergoing IAT from five studies were evaluated. Median logMAR improvement in visual acuity was -0.400 (p < 0.001). There was no significant association between logMAR change and time to treatment when time (hours) was described as a continuous variable or described categorically [0-4, 4-8, 8-12, 12+ h; or 0-6, 6-12, 12+ h]. CONCLUSION: The visual improvement observed in this series had no relationship to the time from symptom onset to treatment with IAT. This suggests that patients may have the possibility for improvement even with delayed presentation to the neurointerventionalist. Other factors, such as completeness of retinal occlusion, may be more important than time to treatment. Additional studies to determine optimal patient selection criteria for the endovascular treatment of acute CRAO are needed.

Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study.

BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. © 2016 International Parkinson and Movement Disorder Society.

Comparison of coliform contamination in non-municipal waters consumed by the Mennonite versus the non-Mennonite rural populations.

OBJECTIVES: Mennonites reside in clusters, do not use modern sewage systems and consume water from non-municipal sources. The purpose of this study is to assess risk of Escherichia coli exposure via consumption of non-municipal waters in Mennonite versus non-Mennonite rural households. METHODS: Results were reviewed for non-municipal water samples collected by the local health department from Mennonite and non-Mennonite lifestyle households from 1998 through 2012. Water contamination was examined with the help of two study variables: water quality (potable, polluted) and gastrointestinal (GI) health risk (none, low, high). These variables were analyzed for association with lifestyle (Mennonite, non-Mennonite) and season (fall, winter, spring, summer) of sample collection. Data were split into two periods to adjust for the ceiling effect of laboratory instrument. RESULTS: From the entire cohort, 82 % samples were polluted and 46 % samples contained E. coli, which is consistent with high GI health risk. In recent years (2009 through 2012), the presence of total coliforms was higher in non-Mennonites (39 %, P = 0.018) and presence of E. coli was higher in Mennonites (P = 0.012). Most polluted samples were collected during summer (45 %, P = 0.019) and had high GI health risk (51 %, P = 0.008) as compared to other seasons. CONCLUSIONS: Majority of non-municipal waters in this region are polluted, consuming those poses a high GI health risk and contamination is prevalent in all households consuming these waters. An association of E. coli exposure with the Mennonite lifestyle was limited to recent years. Seasons with high heat index and increased surface runoffs were the riskiest to consume non-municipal waters.

Evaluating the long-term effect of FOBT in colorectal cancer screening.

BACKGROUND: Cancer screening has been effective in detecting tumors early before symptoms appear. However, the effectiveness of the regular fecal occult blood test (FOBT) in colorectal cancer in the long term has not been quantified. METHODS: We applied the statistical method developed by Wu and Rosner using data from the Minnesota Colon Cancer Control Study (MCCCS). All initially asymptomatic participants were classified into four mutually exclusive groups: true-early-detection, no-early-detection, over-diagnosis, and symptom-free life; human lifetime was treated as a random variable and is subject to competing risks. All participants in the screening program will eventually fall into one of the four outcomes above. Predictive inferences on the percentages of the four outcomes for both genders were made using the Minnesota study data. RESULTS: Depending on gender, screening frequency and age at the initial screening, for all participants the probability of "symptom-free-life" varies between 95.3% and 96.6%; the probability of "true-early-detection" is 1.9-3.8%; the probability of no-early-detection is 0.3-2.0%; the probability of over-diagnosis is 0.16-0.3%. Among those with colorectal cancer detected by regular FOBT, the probability of over-diagnosis is lower than expected and is between 6% and 9%, with 95% CI (2.5%, 21.3%) for females and (1.9%, 44.7%) for males. The probability of true-early-detection increases as screening interval decreases. The probability of no-early-detection decreases as screening interval decreases. CONCLUSION: The probability of over-diagnosis among the screen-detected cases is not as high as previously thought. We hope this outcome can provide valuable information on the effectiveness of the FOBT in colorectal cancer detection in the long term.

Analysis of probe level patterns in Affymetrix microarray data.

BACKGROUND: Microarrays have been used extensively to analyze the expression profiles for thousands of genes in parallel. Most of the widely used methods for analyzing Affymetrix Genechip microarray data, including RMA, GCRMA and Model Based Expression Index (MBEI), summarize probe signal intensity data to generate a single measure of expression for each transcript on the array. In contrast, other methods are applied directly to probe intensities, negating the need for a summarization step. RESULTS: In this study, we used the Affymetrix rat genome Genechip to explore variability in probe response patterns within transcripts. We considered a number of possible sources of variability in probe sets including probe location within the transcript, middle base pair of the probe sequence, probe overlap, sequence homology and affinity. Although affinity, middle base pair and probe location effects may be seen at the gross array level, these factors only account for a small proportion of the variation observed at the gene level. A BLAST search and the presence of probe by treatment interactions for selected differentially expressed genes showed high sequence homology for many probes to non-target genes. CONCLUSION: We suggest that examination and modeling of probe level intensities can be used to guide researchers in refining their conclusions regarding differentially expressed genes. We discuss implications for probe sequence selection for confirmatory analysis using real time PCR.