Accuracy of multislice computed tomography in the preoperative assessment of coronary disease in patients with aortic valve stenosis.

OBJECTIVES: To evaluate multislice computed tomography (MSCT) as an alternative to coronary angiography, we prospectively studied its diagnostic accuracy for the detection of significant coronary artery lesions in patients with significant aortic valve stenosis undergoing valve surgery. BACKGROUND: In patients with aortic valve stenosis, coronary angiography is still recommended before surgery. Multislice computed tomography is a promising noninvasive technique for the detection of significant coronary artery lesions. METHODS: Fifty-five consecutive patients scheduled for coronary angiography in the preoperative assessment of aortic valve stenosis underwent 16-slice MSCT 24 h before coronary angiography. We analyzed coronary lesions, image quality, and arterial calcium score. RESULTS: The sensitivity of the MSCT-based strategy in detecting significant stenosis was 100%, and its specificity 80%. The positive and negative predictive values were respectively 55% and 100%. For calcium scores <1,000 (77% of patients), MSCT detected all patients without coronary artery disease, enabling conventional coronary angiography to be avoided in 35 of 55 cases (80%). For calcium scores >1,000, MSCT enabled conventional coronary angiography to be avoided in only 6% of cases, either because significant stenosis was found with a possible indication of revascularization, or because the examination was not interpretable. CONCLUSIONS: The results of this initial experience in relatively few patients suggest that MSCT-based coronary angiography may serve as an alternative to invasive coronary angiography to rule out significant coronary artery disease in patients scheduled for elective aortic valve replacement. Larger studies are necessary to fully explore the potential of coronary MSCT to improve preoperative risk stratification.     

From the Cover: Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2

In the Ashkenazi Jewish (AJ) population of Israel, 11% of breast cancer and 40% of ovarian cancer are due to three inherited founder mutations in the cancer predisposition genes BRCA1 and BRCA2. For carriers of these mutations, risk-reducing salpingo-oophorectomy significantly reduces morbidity and mortality. Population screening for these mutations among AJ women may be justifiable if accurate estimates of cancer risk for mutation carriers can be obtained. We therefore undertook to determine risks of breast and ovarian cancer for BRCA1 and BRCA2 mutation carriers ascertained irrespective of personal or family history of cancer. Families harboring mutations in BRCA1 or BRCA2 were ascertained by identifying mutation carriers among healthy AJ males recruited from health screening centers and outpatient clinics. Female relatives of the carriers were then enrolled and genotyped. Among the female relatives with BRCA1 or BRCA2 mutations, cumulative risk of developing either breast or ovarian cancer by age 60 and 80, respectively, were 0.60 (± 0.07) and 0.83 (± 0.07) for BRCA1 carriers and 0.33 (± 0.09) and 0.76 (± 0.13) for BRCA2 carriers. Risks were higher in recent vs. earlier birth cohorts (P = 0.006). High cancer risks in BRCA1 or BRCA2 mutation carriers identified through healthy males provide an evidence base for initiating a general screening program in the AJ population. General screening would identify many carriers who are not evaluated by genetic testing based on family history criteria. Such a program could serve as a model to investigate implementation and outcomes of population screening for genetic predisposition to cancer in other populations.Inherited mutations in BRCA1 and BRCA2 predispose to high risks of breast and ovarian cancer. Among female mutation carriers, presymptomatic surgical measures significantly reduce morbidity and mortality (1, 2). In particular, risk-reducing salpingo-oophorectomy (i.e., the removal of ovaries and fallopian tubes from a woman without ovarian cancer) reduces risk both of breast cancer and of ovarian cancer, as well as overall mortality (1). However, for many mutation carriers identified following their first cancer diagnosis, genetic testing was not previously indicated because family history did not suggest inherited cancer predisposition (3–5, 6). From a prevention perspective, it is a missed opportunity to identify a woman as a BRCA1 or BRCA2 mutation carrier only after she develops cancer.Among Ashkenazi (European) Jews (AJ), three mutations, BRCA1 185delAG, BRCA1 5382insC, and BRCA2 6174delT, account for the great majority of inherited cancer risk due to BRCA1 and BRCA2 (7). In the AJ population, 2.5% of persons carry one of these three mutations (8), and the mutations account for 11% of breast cancer (3) and 40% of ovarian cancer (9, 10). These observations suggest that genetic testing in the AJ population for these mutations fulfills WHO criteria for population screening (11, 12): The disease is an important public health burden to the target population; prevalence and attributable risk of disease due to the mutations are known; and effective interventions exist. However, one necessary piece of information remains unknown: What is the disease risk to mutation carriers ascertained from the general population, rather than carriers identified based on family history (13)?Previous studies assessing cancer risks due to mutations in BRCA1 and BRCA2 ascertained carriers through high-incidence families (14), through a single index case with breast or ovarian cancer (3, 15) or through both affected and unaffected carriers (16). In a 1997 study of AJ volunteers, most index cases had no previous cancer diagnosis, but the percentage of index cases with a family history of breast cancer was approximately double that of unselected AJs (17). In principle, these strategies could have yielded risk estimates different from those of carriers ascertained from the local host population, if cancer risk in BRCA1 or BRCA2 carriers were influenced by familial factors other than the BRCA1 or BRCA2 mutation, such as modifier genes or shared environment (18). In addition, in almost all of these studies, risk estimates were based on imputing carrier status, rather than on direct genetic testing of BRCA1 and BRCA2. This year, the Recommendation Statement on BRCA Testing from the US Preventive Services Task Force recommended against population screening for BRCA1 and BRCA2 mutations, because cancer risk to mutation carriers in the general population was not yet known (19). To address this gap, in this study we assessed breast and ovarian cancer risks in confirmed carriers of BRCA1 and BRCA2 mutations ascertained from the general population. The study was undertaken in the AJ population, because screening for only three founder mutations is sufficient to capture nearly all inherited cancer risk in this population due to BRCA1 and BRCA2 (7).     

The disproportionate burden of HIV and STIs among male sex workers in Mexico City and the rationale for economic incentives to reduce risks

Introduction

The objective of this article is to present the rationale and baseline results for a randomized controlled pilot trial using economic incentives to reduce HIV and sexually transmitted infection (STI) risk among male sex workers (MSWs) in Mexico City.

Methods

Participants (n=267) were tested and treated for STIs (chlamydia, gonorrhoea, syphilis and HIV) and viral hepatitis (hepatitis B and C), received HIV and STI prevention education and were randomized into four groups: (1) control, (2) medium conditional incentive ($50/six months), (3) high conditional incentive ($75/six months) and (4) unconditional incentive ($50/six months). In the conditional arms, incentives were contingent upon testing free of new curable STIs (chlamydia, gonorrhoea and syphilis) at follow-up assessments.

Results

Participants’ mean age was 25 years; 8% were homeless or lived in a shelter, 16% were unemployed and 21% lived in Mexico City less than 5 years. At baseline, 38% were living with HIV, and 32% tested positive for viral hepatitis or at least one STI (other than HIV). Participants had a mean of five male clients in the previous week; 18% reported condomless sex with their last client. For 37%, sex work was their main occupation and was conducted mainly on the streets (51%) or in bars/discotheques (24%) and hotels (24%). The average price for a sex transaction was $25 with a 35% higher payment for condomless sex.

Conclusions

The findings suggest that economic incentives are a relevant approach for HIV prevention among MSWs, given the market-based inducements for unprotected sex. This type of targeted intervention seems to be justified and should continue to be explored in the context of combination prevention efforts.     

Detection of Cerebral Hyperperfusion Syndrome after Carotid Endarterectomy with CT Perfusion

We present the case of a 60‐year‐old female patient, who developed symptomatic internal carotid artery stenosis and subsequently underwent carotid endarterectomy. Four days after an uneventful surgery the patient developed confusion, seizures, and was admitted to the ICU. CT perfusion revealed reduced ispilateral time‐to‐peak and mean‐transient‐time and increased cerebral blood volume and cerebral blood flow, confirming the diagnosis of cerebral hyperperfusion syndrome. We thus propose CT perfusion as a diagnostic means for cerebral hyperperfusion syndrome, a syndrome that remains underdiagnosed.     

Definition of pulmonary embolism‐related death and classification of the cause of death in venous thromboembolism studies: Communication from the SSC of the ISTH

Pulmonary embolism (PE)‐related death is often a component of the primary outcome in venous thromboembolism (VTE) clinical studies. Definitions for PE‐related death vary widely, which may lead to biased risk estimates of clinical outcomes, thereby affecting both internal and external validity of study results. We here provide a standardized definition of PE‐related death and propose guidance for classification and reporting of the cause of death for clinical studies in VTE. The proposal was developed in a four‐step process, including a systematic review of definitions used for PE‐related death in previous studies, two subsequent surveys with VTE experts, and meetings held within the Scientific and Standardization Committee (SSC) working group until consensus on the proposal was reached. The proposed classification comprises three categories: Category A: PE‐related death, category B: undetermined cause of death, and category C: cause of death other than PE. Category A includes A1: autopsy‐confirmed PE in the absence of another more likely cause of death; A2: objectively confirmed PE before death in the absence of another more likely cause of death; and A3: PE is not objectively confirmed, but is most likely the main cause of death. Category B includes B1: cause of death is undetermined, despite available information; and B2: insufficient clinical information available to determine the cause of death. The use of the proposed definition will hopefully improve the accuracy of study outcomes, between‐study comparisons, meta‐analyses, and validity of future clinical VTE studies.