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The purpose of this study was to examine sex-based trends in incidence of elective abdominal aortic aneurysm (AAA), ruptured AAA, ruptured AAA repair and AAA-related mortality.A retrospective analysis of patients presenting with AAA from 2005-2015 was conducted. Rates of elective AAA repair, ruptured AAA, ruptured AAA repair, and mortality were obtained from linking provincial administrative data using medical services insurance billing number. The age-adjusted incidence of elective AAA repair, overall rate of ruptured AAA, ruptured AAA repair, and AAA-related mortality was calculated for each sex based on Canadian census estimates, adjusted to the Canadian standard population. Weighted linear regression was performed to analyze trends in incidence over time.1986 elective AAA repairs were identified, of which 1098 were repaired open and 898 endovascular AAA repair (EVAR). 570 ruptured AAAs were identified, of which 295 (52%) were repaired: 259 open and 36 EVAR. The proportion of ruptured AAA that was repaired did not change over time (p=0.54). The proportion repairs performed using EVAR increased significantly in both elective (p0.001) and rupture repairs (p0.001). During the study period, 662 patients died of AAA-associated mortality. The average incidence of elective AAA repair in men was 29.3 (95% CI: 27.8 to 30.8) per 100,000 and decreased over time (p=0.04), whereas the average incidence in women was 9.2 [8.3 to 10.0] and stable (p=0.07). The incidence of open elective AAA repair was 10.5 [9.9-11.1] with a decreasing trend over time (p0.001) and EVAR was 9.0 (8.5-9.6) with an increasing trend over time (p0.001). A decreasing trend of overall ruptured AAA (5.4 [5.0-5.9], p0.001), ruptured AAA repair (2.9 [2.5-3.2], p=0.02), and of AAA-related mortality (6.2 [5.8-6.8], p0.001) was found, with consistent trends in both sexes. The incidence of open ruptured AAA repair decreased over time (p=0.001) whereas the incidence of ruptured EVAR remained stable (p=0.23).The incidence of elective AAA repair is decreasing in males but not females, whereas the incidence of rupture has decreased in both sexes. This has translated into reduced incidence of AAA-related mortality. Increased adoption of EVAR for ruptured AAA should continue these trends.

Ruptured abdominal aortic aneurysms (RAAAs) are surgical emergencies that require immediate and expert treatment. It has been unclear whether presentation during evenings and weekends, when "on call" teams are primarily responsible for patient care, is associated with worse outcomes. Our objective was to evaluate the outcomes of patients presenting with RAAAs after-hours vs during the workday.A retrospective cohort study of all RAAAs in Nova Scotia between 2005 and 2015 was performed through linkage of administrative databases. Patients who had presented to the hospital with RAAAs during the workday (Monday through Friday, 6 am to 6 pm) were compared with those who had presented after-hours (6 pm to 6 am during the week and on weekends). The baseline and operative characteristics were identified for all patients through the available databases and a review of the medical records. Mortality before surgery, 30-day mortality, and operative mortality were compared between groups using multivariable logistic regression, adjusting for factors clinically significant on univariable analysis.A total of 390 patients with RAAAs were identified from 2005 to 2015, of whom 205 (53%) had presented during the workday and 185 (47%) after-hours. The overall chance of survival (OCS) was 45% overall, 49% if admitted to hospital, and 64% if surgery had been performed. During the workday, the OCS was 43% overall, 48% if admitted to hospital, and 67% if surgery had been performed. After-hours, the OCS was 46% overall, 49% if admitted to hospital, and 61% if surgery had been performed. Mortality before surgery was increased for patients who had presented to the hospital during the workday compared with after-hours (36% vs 26%; P = .04). The 30-day mortality (57% vs 54%; P = .62), rates of operative management (63% vs 72%; P = .06), and operative mortality (33% vs 39%; P = .33) were similar between the workday and after-hours groups (57% vs 54%; P = .06). After adjusting for significant clinical variables, the patients who had presented with RAAAs after-hours had had a similar odds of dying before surgery (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.41-1.03), operative management (OR, 1.47; 95% CI, 0.93-2.31), 30-day mortality (OR, 0.98; 95% CI, 0.63-1.51), and operative mortality (OR, 1.33; 95% CI, 0.78-2.26). In the subgroup of patients presenting to a hospital with endovascular capabilities, patients presenting after-hours had had similar odds of 30-day mortality (OR, 1.07; 95% CI, 0.57-2.02), and operative mortality (OR, 1.14; 95% CI, 0.58-2.23).We found that patients presenting to the hospital with RAAAs after-hours did not have increased adjusted odds of mortality before surgery, operative management, 30-day mortality, or operative mortality.

Centralization of vascular surgery care for Ruptured Abdominal Aortic Aneurysms (RAAAs) to high volume tertiary centers may hinder access to timely surgical intervention for patients in remote areas. The objective of this study was to determine the association between distance from vascular care and mortality from RAAA in the province of Nova Scotia, Canada.A retrospective cohort study of all RAAAs in Nova Scotia between 2005 and 2015 was performed through linkage of administrative databases. Patients were divided into groups by estimated travel time from their place of residence to the tertiary center (1 hour and ≥1 hour) using geographic information software. Baseline and operative characteristics were identified for all patients through available databases and completed through chart review. Mortality at home, during transfer to the vascular center and overall 30-day mortality were compared between groups using t-test and chi-squared test, as appropriate. Multivariable logistic regression analysis was used to calculate the independent effect of travel time on survival outcomes.A total of 567 patients with RAAA were identified from 2005-2015, of which 250 (44%) resided1 hour travel time to the tertiary center and 317 (56%) resided ≥1 hour. On multivariable analysis, travel time ≥1 hour from vascular care was an independent predictor of mortality at home (OR 1.68, 95% CI 1.07-2.63, p=0.02), mortality prior to operation (OR 2.64, 95% CI 1.81-3.83, p0.001), and overall 30-day mortality (OR 1.61, 95% CI 1.10-2.37, p=0.02). In patients who received an operation (n=294), there was no association between increased travel time and mortality (OR 1.02, 95% CI 0.60-1.73, p=0.94).Travel time ≥1 hour to the tertiary center is associated with significantly higher mortality from ruptured AAA. However, there was no difference in overall chance of survival between groups for patients that underwent AAA repair. Therefore, strategies to facilitate early detection and timely transfer to a vascular surgery center may improve outcomes for patients with RAAA.

Radial artery access has experienced increasing adoption and rapid expansion of indications for neurointerventional procedures. This access is an attractive neurointervention route to be considered, with many advantages over the traditional femoral access in terms of ease of vasculature navigation and decreased risk of complications such as significant bleeding. Although a promising technique for neurointerventional procedures, there are inherent and unique considerations as well as potential complications involved. The following case report highlights some of these vital concepts associated with radial artery access, including appropriate patient selection as well as assessment of arterial size in the context of neurointerventional techniques. Early identification of complications such as arterial injury and compartment syndrome, with an emphasis on appropriate draping and inter-procedure monitoring, is discussed as well as approaches for subsequent management. Finally, the issue of radiation safety in this emerging technique is considered. These concepts are critical for the successful use and the continued growth of radial artery access for neurointervention procedures.

Objective: The haptoglobin (Hp)2-2 phenotype (~35-40% of people) is associated with increased oxidation and dysfunctional high-density lipoprotein (HDL) in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL-cholesterol and lower triglycerides have not reliably prevented cardiovascular disease (CVD) in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the ACCORD lipid trial (NCT00000620). Research Design and Methods: Cox proportional hazards regression models quantitfied the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n=1,795) separately from those without (n=3,201). Results: Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable-adjusted hazard ratio: 0.74, 95% CI: 0.60-0.90, compared to no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16, 0.87-1.56, p, interaction=0.009). Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non-Hp2-2 phenotype group was most effective in participants with severe dyslipidemia (p, interaction=0.01), and and in males (p, interaction= 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (p, interaction= 0.002). Conclusions: The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.

Background This study sought to determine the impact of the pandemic response to healthcare delivery on outcomes in patients with cardiovascular disease. Methods This is a population-based cohort study performed in the province of Nova Scotia (population 979,499), between Pre-COVID (March 1, 2017 – March 16, 2020) and in-COVID (March 17, 2020 – December 31, 2020) periods. Adult patients (≥18 years) with new onset or existing cardiovascular disease were included for comparison between periods. The main outcome measures included: cardiovascular emergency department visits or hospitalizations, mortality, and out-of-hospital cardiac arrest. Results In the first month of the in-COVID period, emergency department visits (n=51,750) for cardiac symptoms decreased by 20.8% (95% CI 14.0% - 27.0%, p, Restrictions in healthcare resources due to COVID-19 was associated with increased morbidity/mortality in patients with cardiovascular disease. In a population with low burden of COVID-19 disease, increased rates of out-of-hospital cardiac arrest and myocardial infarction were observed, with increased mortality in patients awaiting coronary revascularization procedures. As the world recovers from the pandemic, steps should be taken to inform policy surrounding healthcare delivery for future pandemic relief and an increased burden of cardiovascular disease.

Night eating syndrome (NES) is characterized by evening hyperphagia and/or nocturnal ingestion. The main objective of this study was to assess the percentage of students complying with symptoms and behaviors consistent with the diagnostic criteria for NES, and explore its association with body mass index (BMI), dietary habits, physical activity, smoking status, and sleep patterns, among a sample of college students. A cross-sectional survey was conducted among a sample of 413 undergraduate students, mean age of 20.6 ± 1.68 SD, at Central Michigan University. Students completed an online survey including demographic information and the Night Eating Diagnostic Questionnaire (NEDQ) and Pittsburgh Sleep Quality Index Questionnaire (PSQI). Participants were grouped based on self-reporting of the presence and frequency of night eating-related symptoms and behaviors related to the diagnostic criteria for NES as follows: normal, mild night eater, moderate night eater, and full-syndrome night eater. Pearson’s Chi-squared, Student’s t test, and Wilcoxon rank-sum test were used to test the association between students with and without any night eating behavior in relation to BMI, lifestyle variables, and sleep duration/quality. Results showed that the proportion of students complying with symptoms and behaviors consistent with full-syndrome of NES was 1.2%. There were no significant differences between students complying with symptoms and behaviors consistent with any level of NES and those without any night eating behavior regarding BMI, eating habits, physical activity, and smoking status. NES was significantly related to sleep duration (P = 0.023). Students complying with symptoms consistent with any level of NES reported shorter sleep time and had higher total PSQI score (6.73 ± 4.06) than students without the syndrome (5.61 ± 2.61) (P = 0.007). Although the percentage of students complying with full-syndrome NES was relatively low in our student sample, those students had shorter sleep time and poorer sleep quality than the other groups. However, it is unclear whether evening hyperphagia is a response to a lack of sleep or vice versa, and further research is needed. Level III, case-control analytic study.

In light of the advances in HCV therapy, simplification of diagnosis confirmation, pre- treatment diagnostic workup and treatment monitoring is required to ensure broad access to interferon-free therapies. HCV core antigen (HCV cAg) testing is rapid, giving results in approximately 60min, and less expensive than HCV RNA methods. While extensive data on the analytical performance of HCV cAg relative to RNA or comparisons in longitudinal studies of patients on interferon based (response guided) therapy there is very limited data on the relative performance of HCV cAg in diagnosis and monitoring patients receiving all-oral interferon free regimens. Furthermore, there is no data in the literature that describes the specificity of HCV cAg in patients with resolved HCV infection i.e. anti-HCV positive/HCV RNA negative. In this study a total of 1201 plasma samples from the 411 HCV genotype 1 subjects with a HCV RNA viral load >50,000IU/ml who enrolled in a clinical trial with ombitasvir, ritonavir-boosted paritaprevir and dasabuvir, with or without ribavirin were retrospectively tested in a blinded fashion with HCV cAg test and results were compared to HCV RNA levels. The specificity of the HCV cAg test was also evaluated in anti-HCV positive but HCV RNA negative samples. Overall concordance between HCV cAg and HCV RNA was 98.6% while concordance in pre-treatment samples was 99.5% (409/411; n=2 HCV RNA pos. with viral loads>3 Mill IU/ml but HCV cAg neg.) and 99.24% in post treatment week 12 samples (391/394; n=2 HCV RNA pos.

Approval of Ledipasvir/Sofosbuvir for the treatment of chronic hepatitis C (HCV) includes the truncation of therapy from 12 to 8 weeks in treatment naïve, non-cirrhotic patients with baseline HCV RNA levels

The Abbott RealTi m e HIV-1 viral load assay uses primers and probes targeted to integrase, which is also the target of integrase inhibitors such as raltegravir. Viral loads of 42 raltegravir-susceptible and 40 raltegravir-resistant specimens were determined using RealTi m e HIV-1 and Roche Monitor (v1.5). The differences in viral load measurements between assays were comparable in the two groups, demonstrating that the RealTi m e HIV-1 assay can tolerate raltegravir-selected mutations.

International audience; Maternal tobacco consumption is considered as a risk factor for nonsyndromic oral clefts. However, this risk is moderate and may be modulated by genetic susceptibilities, including variants of the TGFA, TGFB3 and MSX1 developmental genes and polymorphisms of genes of the CYP (1A1, 2E1) and GST (M1, T1) families involved in metabolic pathways of tobacco smoke compounds. This French case-control study (1998-2001; 240 nonsyndromic cases, 236 controls) included a case-parent design (175 triad-families) that made it possible to distinguish the direct effect of the child's genotype and maternally mediated effects. Maternal smoking during the first trimester of pregnancy was not associated with the oral cleft risk in this population, but we observed statistically significant increased risks associated with maternal exposure to environmental tobacco smoke (ETS). No variant of any of the three developmental genes was significantly associated with oral cleft. The fetal CYP1A1*2C variant allele was associated with a statistically significant decreased risk, compared with the homozygous wild-type: relative risk = 0.48, 95% confidence interval: 0.2, 1.0. Suggestive reduced risks were also observed for the maternal CYP1A1*2C allele and the fetal CYP2E1*5 allele. The GSTM1 and GSTT1 deletions appeared to play no role. Our findings suggest some interactions, with the strongest between ETS and CYP1A1 or MSX1 and between maternal smoking and CYP2E1. We did not confirm the maternal smoking-infant GSTT1 null interaction previously reported by other investigators.

Background The introduction of highly potent direct-acting combination therapies for HCV have negated the role of response-guided therapy and reduced the role of treatment monitoring. However, there remains a need to identify patients who are actively infected with HCV and discriminate those who have achieved sustained virological response (SVR) from those who fail to achieve SVR. Methods A total of 1,678 plasma samples from the 631 subjects enrolled in AbbVie's SAPPHIRE I trial (NCT01716585) were tested in a blinded fashion with Abbott HCV core antigen (cAg) assay and results were compared with Roche High-Pure system/COBAS® TaqMan HCV RNA 2.0 assay. Results Using 10 fmol/l as the clinical cutoff for cAg, the HCV RNA and cAg tests were in 100% agreement for true negative samples and 99.6% agreement for truly positive samples. One discordant (screening) sample was identified. This sample was target not detected by HCV RNA method but positive by anti-HCV and highly positive by ARCHITECT core antigen (7,912 fmol/l). Seventeen samples had cAg levels in the ‘grey zone’ >3 but 3 but Conclusions In this study cAg, with a 10 fmol/l cutoff, accurately identified 99.6% of patients with active viraemia and discriminated all subjects who achieved SVR from those who failed therapy.

International audience; The association between maternal folate intake and risk of nonsyndromic oral clefts has been studied among many populations with conflicting results. The methylenetetrahydrofolate reductase gene (MTHFR) plays a major role in folate metabolism, and several polymorphisms, including C677T, are common in European populations. Data from a French study (1998-2001) let us investigate the roles of maternal dietary folate intake and the MTHFR polymorphism and their interaction on the risk of cleft lip with/without cleft palate (CL/P) and cleft palate only (CP). We used both case-control (164 CL/P, 76 CP, 236 controls; 148, 59, 168 of whom, respectively, had an available genotype) and case-parent (143 CL/P and 56 CP families) study designs and distinguished the role of the child's genotype and maternally mediated effects on risks. This study observed a beneficial effect of mothers' dietary folate intake on their offspring's risk (odds ratio (OR)(< or = 230 microg/day) = ref; for CL/P, OR([230-314 microg/day]) = 0.56, 95% confidence interval = 0.3-0.9, OR(>314 microg/day) = 0.64, 0.4-1.1; for CP, OR([230-314 microg/day]) = 1.15, 0.6-2.2, OR(>314 microg/day) = 0.70, 0.3-1.4). We observed a reduced risk associated with the TT genotype of the child in the case-control analysis (OR(CC) = ref; for CL/P, OR(TT) = 0.54, 0.3-1.1; for CP, OR(TT) = 0.33, 0.1-1.0); this genotype, either fetal or maternal, was not statistically significant in the case-parent analysis. A frequency of TT genotype higher in our control group than previously reported in France can partly explain the risk reduction observed in case-control comparison. Interactions were not statistically significant. Stratified case-parent analysis showed, however, slight heterogeneity in the role of TT genotype according to folate intake. The modest sample size limits this study, which nonetheless provides new estimate of the possible impact of dietary folate intake and MTHFR polymorphism on oral clefts.

Less-invasive and endovascular approaches to cardiovascular disease are burgeoning, and the lesson from coronary interventions is clear: patients are willing to accept higher reintervention rates for less-invasive initial procedures.InthisissueoftheJournal,NguyenandGeorgeargue that training in our field must be revised to accommodate the explosion of percutaneous technology. 1 We concur and further suggest that until training programs catch up to the changing demands of the profession, surgeons in training must commit dedicated time to acquiring these skills. Similar to the expanding scope of the contemporary valve surgeon, today’s aortic surgeon will offer both minimally andmaximallyinvasivesurgeries.Formanypatients,opensurgical aortic repair remains the gold standard and provides excellent, durable results. The role for thoracic endovascular aortic repair, however, is expanding: thoracic endovascular aortic repair isfirst-line therapy in many descending aortic pathologies; thoracoabdominal aneurysms can be managed with fenestrated or branched grafts; stenting may be offered to patients with high-risk arch and ascending pathology; and the endoscopic Bentall procedure will undoubtedly make its appearance.Itisourpositionthatasurgeonwhoisabletooffer the full spectrum of therapeutic options for complex aortic pathologies is optimally positioned to consider and deliver what isinthebestinterestofeachpatient.Incorporatingtheevolving endovascularskillsetintothecardiactrainees’repertoire,however, poses a unique challenge for residency programs. For nearly 2 decades, Canadian cardiac surgical training programs have consisted of direct-entry 6-year residencies, similar to the current American I-6 programs. Advantages of the Canadian system include the following: (1) early and intensiveexposuretocardiologywiththemajorityofajunior year spent in the coronary care unit, echocardiography laboratory, angiography suite, and electrophysiology laboratory, a formative time that has become an important part of the development of a cardiac surgeon; (2) an enrichment year, designed to cultivate a resident’s academic or clinical interests;and,mostimportantly(3)built-inflexibility,allowing programs to adapt and stay relevant to the contemporary cardiac surgical environment. It is feasible, for example, for programs to dedicate as much as 6 months of senior training to endovascular surgery or transcatheter aortic valve replacement (TAVR) rotations, something that would not bepossiblewiththetimeconstraintsofa2-or3-yeartraining program after general surgery. Another adaptation has been thetransitionin thelastdecade towardtraining cardiovascularratherthancardiothoracicspecialists.Astherequirement for oncologic expertise and thoracoscopic and laparoscopic skills expands, cardiac surgeons bear increasing similarity to their vascular rather than thoracic surgical colleagues with regard to disease pathology and surgical techniques. The inherent delay between the development of a novel techniqueordeviceanditswidespreadadoptioncreatesinevitable challenges for training. Emerging technologies are often first implemented in major centers or in the context of clinical trials before gaining momentum and becoming widelydisseminated.Trainingparadigmsreflectthisprocess, and the opportunities initially available for trainees may be limited.The acquisitionofnewskillsetsisdifficultandoften occurs in descending order of priority: an attending in practice, an advanced fellow spending dedicated time learning a procedure, and finally, often low on the totem pole, a junior

International audience; OBJECTIVES: To examine the association between maternal occupational exposure to mixtures of organic solvents during pregnancy and the risk of non-syndromic oral clefts. METHODS: A case-control study (164 cleft lip with/without cleft palate (CL/P), 76 cleft palate (CP), 236 controls) was conducted in France to investigate the role of maternal occupational exposure to organic solvents at the beginning of pregnancy in the risk of non-syndromic oral clefts. An expert chemist, guided by a detailed description of the women's occupational tasks, assessed exposure for each. Analysis of the findings used logistic regression. RESULTS: In the control group, 39% of the women who reported working during pregnancy were exposed to at least one type of organic solvent. The risk of oral clefts was associated with oxygenated (for CL/P: OR = 1.8, 95% CI 1.1 to 2.9; and for CP, OR = 1.4, 95% CI 0.7 to 2.7), chlorinated (OR = 9.4, 95% CI 2.5 to 35.3; OR = 3.8, 95% CI 0.7 to 20.7), and petroleum (OR = 3.6, 95% CI 1.5 to 8.8; OR = 1.2, 95% CI 0.3 to 4.9) solvents. The risk of oral clefts increased linearly with level of exposure within the three subgroups of oxygenated solvents we considered (aliphatic alcohols, glycol ethers, and other oxygenated solvents, including esters, ketones, and aliphatic aldehydes). CONCLUSIONS: Results suggest that maternal occupational exposure to organic solvents during pregnancy may play a role in the aetiology of oral clefts. The limited number of subjects and the problem of multiple exposures require that these results be interpreted cautiously.

Background Application of response-guided therapy (RGT) rules to the treatment of HCV infection with pegylated interferon-α2a and ribavirin, and direct-acting antivirals (DAAs) such as the NS3/4A protease inhibitors (PIs) boceprevir and telaprevir, relies on the determination of viral genotype and on-treatment HCV RNA level. Currently there are few data available regarding the clinical impact of the analytical differences that exist between different HCV RNA quantification assays on treatment decisions such as those involved in RGT. Methods We sought to ascertain the concordance between two HCV RNA quantification assays, the Roche/ High-Pure-System COBAS® TaqMan (CTM) version 2 and Abbott RealTi me HCV (ART), and to understand the impact of different assay characteristics on treatment decisions. We evaluated 1,336 specimens collected from 74 patients enrolled in the Phase II CHAMPION-2 study of the investigational DAAs ABT-450 (an acylsulfonamide NS3/4A PI), ABT-072 and ABT-333 (both non-nucleoside NS5B polymerase inhibitors). Results HCV RNA level results were highly correlated, but CTM values were higher than those from ART by an average of 0.46 log IU/ml. Use of ART HCV RNA level results led to a higher positive predictive value of week 4 viral load for the achievement of a sustained virological response 24 weeks after the end of treatment (100% versus 87% using the lower limit of detection as the threshold). Conclusions This study suggests that HCV viral load assay performance characteristics need to be taken into consideration when managing HCV patients with RGT. Further studies are required to determine whether a consensus HCV RNA level threshold can be established or whether HCV viral load assays with greater sensitivity can increase cure rates with RGT.

Monitoring the serum hepatitis B viral DNA levels with sensitive realtime PCR assays is strongly recommended for the management of patients with chronic HBV infection. This study compares the performance of two realtime HBV quantitative PCR assays with samples from chronic HBeAg(+) and HBeAg(−) patients.

Studies have demonstrated that plasma samples collected and stored frozen using vacutainer plasma preparation tubes (PPT) may result in falsely elevated viral load (VL) values with the Roche COBAS TaqMan HIV-1 v1.0 test. At the University of Connecticut Health Center, a total of 349 samples from HIV-1-infected patients on HAART were collected and stored frozen in PPT. Viral load (VL) results were obtained using the Roche COBAS TaqMan HIV-1 v2.0 test (CTM v2.0) and Abbott RealTime HIV-1 assay (RealTime HIV-1). Of the 349 samples, 260 (74.5%) had VL values that differed by >0.5log10copies/mL; 64 of these were quantified by both assays. The remaining 196 samples were detected by CTM v2.0 but not detected in RealTime HIV-1: 62 of the most discordant samples in this category (CTM v2.0 detected/RealTime HIV-1 not detected) were further analyzed using two nested RT-PCR assays targeting pol integrase: full-length (864nt) and a highly conserved subregion (134nt). No HIV-1 RNA was detected in the discordant samples, confirming RealTime HIV-1 results. The increase in VL reactivity with the CTM v2.0 assay was presumably due to proviral DNA captured by the CTM total nucleic acid extraction chemistry but not the RNA-specific extraction procedure used in RealTime HIV-1. These results suggest that using CTM v2.0 with samples frozen in PPT could have significant clinical implications for HIV-1 patient management.

International audience

A 53-year-old woman presented with unstable coronary artery disease and severe peripheral vascular disease that prevented brachial, axillary, and femoral access for coronary angiography. Intensive medical management failed with ongoing angina, dynamic ECG changes, hemodynamic instability, and biochemical evidence of reinfarction. Coronary artery bypass grafting was performed without preoperative angiography. Each major coronary territory was grafted. The patient recovered postoperatively without angina at 1-year follow-up.

BACKGROUND Maternal alcohol consumption has been associated with an increased risk of nonsyndromic oral clefts in some studies. Study of gene-environment interaction may provide insight into the reasons for their discrepancies observed. We focused on a polymorphism of the ADH1C gene (third gene of the class I alcohol dehydrogenase family), involved in the metabolism of ethanol and other alcohols. METHODS Data come from a French case-control study (1998–2001), which tested the association between maternal alcohol consumption during the first trimester of pregnancy and the risk of nonsyndromic oral clefts (240 cases, 236 controls). A case-parent study design looked at the association with an ADH1C polymorphism (Ile349Val site) and potential gene-environment interaction effects. A log-linear model was used to distinguish the direct effect of the child's genotype from the maternally mediated effects. RESULTS An increased risk of nonsyndromic oral clefts was observed for women who reported drinking alcohol during the first trimester, compared with women who did not. The mutated ADH1C allele carried by the child seemed to have a protective effect against the risk of oral clefts (RRone copy, 0.71; 95% confidence interval [CI], 0.50–1.02; RRtwo copies, 0.63; 95% CI, 0.3–1.3). The maternal genotype played a less important role than the child's, and its action remains unclear. No significant evidence of interaction effects between the ADH1C genotype and maternal alcohol consumption was observed. CONCLUSIONS Because the ADH1C gene is involved in the metabolic pathways of many alcohols, we propose several hypotheses about the causal pathway, including ethanol oxidation activity and, more probably, retinol oxidation. Birth Defects Research (Part A), 2005. © 2005 Wiley-Liss, Inc.

e21060 Background: Rearrangements of ALK gene on chromosome 2p23 create a constitutively activated tyrosine kinase implicated in the development of NSCLC and targeted by novel therapeutic agents. The Vysis ALK Break Apart (BAP) FISH Probe assay was developed to detect chromosome 2p23 rearrangements in NSCLC FFPE tissue by fluorescence in situ hybridization. Performance of the ALK assay was assessed on FFPE tissue specimens and FFPE cell lines. The ALK probe was also tested on lung cytology cell suspensions. Methods: The ALK FISH assay success rate on primary NSCLC was tested with 30 FFPE tumor resection specimens, four 5-μm section slides each, judged by qualitative rating of fluorescent signal specificity, intensity, and background. Assay performance was further assessed on 15 FFPE biopsy specimens of 4 metastatic sites including mediastinal and axillary lymp nodes, pleural cavity, brain, and adrenal gland. Each specimen was tested in duplicate and evaluated by 2 reviewers. Assay reproducibility on FFPE cell pellets was tested with 3 lots of ALK Negative and ALK Positive Control Slides (cell lines) on 5 non-consecutive days. Slides were enumerated by 3 reviewers to determine % ALK positive cells, to a total of 45 results per control slide type. Additionally, the ALK BAP probe was tested with a modified assay protocol on ThinPrep lung cytology samples from 8 specimens. Results: The assay success rate on FFPE resection specimens was 99.2 % (90% CI 96.1% - 100%). The core biopsy specimens yielded 95% overall success rate. All Control Slides (FFPE cell lines) tested in the reproducibility study were enumerable within assay ranges, and were correctly classified per specifications of 0-8% and ≥20% ALK positive cells in ALK Negative and ALK Positive Control Slides, respectively. All of the lung cytology specimens prepared by ThinPrep hybridized successfully, however 2 specimens had low cellularity for ALK enumeration. Conclusions: The Vysis ALK BAP FISH assay demonstrated reproducible performance on FFPE cell lines and was shown to yield interpretable results on FFPE lung tissue specimens retrieved by resection or biopsy, from primary tumor or metastatic sites. Feasibility using lung cytology cell suspensions was demonstrated.