Inverse correlation between coronary and retinal blood flows in patients with normal coronary arteries and slow coronary blood flow

Background

The “Slow Coronary Flow” (SCF) phenomenon in the presence of angiographically normal coronaries is attributed to microvascular and endothelial dysfunction. The microcirculation can be non-invasively assessed by measuring retinal blood flow velocity.The aim of the present study was to evaluate the efficacy of the “Retinal Functional Imager” (RFI) device as a noninvasive method of diagnosing patients with slow coronary flow.

Methods

Coronary blood flow velocity assessed by corrected TIMI Frame Count and retinal arterioles blood flow assessed by RFI were measured in 28 consecutive patients with normal coronary arteries. The patients were divided into 2 groups: a slow coronary flow (SCF) and a normal coronary flow (NCF) groups.

Results

Inverse correlation was found between retinal and coronary blood flows so that higher retinal arterial flow velocity was observed in the SCF group (3.8 ± 1.1 mm/s vs. 2.9 ± 0.61 mm/s, respectively, p = 0.022). RFI provided 73% sensitivity and 77% specificity for diagnosing SCF using ROC analysis. Additionally, patients with SCF had higher values of serum LDL cholesterol (104.7 ± 18.93 mg/dl vs. 81.55 ± 14.62 mg/dl in NCF, p = 0.005), Glucose (96.9 ± 23.0 mg/dl vs. 83.55 ± 9.7 mg/dl in NCF, p = 0.024), and lower percentage of statin consumption (40.0% vs. 76.9% in NCF, p = 0.049).

Conclusions

Slow coronary blood flow can be non-invasively diagnosed with Retinal Functional Imager. Patients with normal coronary arteries and slow coronary blood flow have high retinal arteriolar blood flow. Early non-invasive diagnosis of SCF might help detect individuals who are at higher risk to develop coronary atherosclerosis, and to provide them with early preventive measures.     

Obstructive Sleep Apnea and Cardiovascular Comorbidities: A Large Epidemiologic Study

Obstructive sleep apnea (OSA) is a common disorder, characterized by cyclic cessation of airflow for 10 seconds or more. There is growing awareness that OSA is related to the development and progression of cardiovascular disease. However, only a few studies have associated OSA directly to major cardiovascular events. The aim of this study was to evaluate the relationship between OSA and cardiovascular morbidity in a well defined population of patients.The electronic database of the central district of a major health management organization was searched for all patients diagnosed with OSA in 2002–2010. For each patient identified, an age- and sex-matched patient was randomly selected from the members of the same health management organization who did not have OSA. Data on demographics, socioeconomic status, and relevant medical parameters were collected as well.The study population included 2797 patients, average age 58.1, in which 76.6% were males. There was a significant correlation between OSA and the presence of ischemic heart disease (P < 0.001), pulmonary hypertension (P < 0.001), congestive heart failure (P < 0.001), cardiomyopathy (P = 0.003), and arrhythmia (P < 0.001). OSA was also significantly correlated with low socioeconomic status (P < 0.001).OSA and cardiovascular disease were strongly correlated. As such, early diagnosis and treatment of OSA may change the course of both diseases. We suggest that sleep disordered breathing should be routinely assessed in patients with cardiovascular problems. An ear–nose–throat evaluation may also be important to rule out anatomic disorders that cause upper airway obstruction.     

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).     

Characterization and antibacterial properties of N-halamine-derivatized cross-linked polymethacrylamide nanoparticles

N-halamine-derivatized cross-linked polymethacrylamide nanoparticles with sizes ranging between 18 ± 2.0 and 460 ± 60 nm were prepared via surfactant-free dispersion co-polymerization of methacrylamide (MAA) and the cross-linking monomer N,N-methylenebisacrylamide (MBAA) in an aqueous continuous phase, followed by a chlorination process using sodium hypochlorite. The effect of various polymerization parameters (monomer concentration, initiator type and concentration, polymerization duration, polymerization temperature, and the weight ratio [MBAA]/[MAA]) on the size and size distribution of the produced cross-linked P(MAA–MBAA) nanoparticles was elucidated. The effect of various chlorination parameters (hypochlorite concentration, chlorination period and temperature) on the bound oxidative chlorine atom (Cl) content of the P(MAA–MBAA) nanoparticles was also investigated. The bactericidal activity of these chloramine-derivatized nanoparticles was tested against two common bacterial pathogens (Escherichia coli and Staphylococcus aureus), and they were found to be highly potent. Furthermore, these nanoparticles also exerted their antimicrobial activity against multi-drug resistant (MDR) bacteria, further demonstrating their efficacy.     

Nuclear wastewater decontamination by 3D-Printed hierarchical zeolite monoliths

The selective removal of radioactive cationic species, specifically ¹³⁷Cs⁺ and ⁹⁰Sr²⁺, from contaminated water is critical for nuclear waste remediation processes and environmental cleanup after accidents, such as the Fukushima Daiichi Nuclear Power Plant disaster in 2011. Nanoporous silicates, such as zeolites, are most commonly used for this process but in addition to acting as selective ion exchange media must also be deployable in a correct physical form for flow columns. Herein, Digital Light Processing (DLP) three-dimensional (3D) printing was utilized to form monoliths from zeolite ion exchange powders that are known to be good for nuclear wastewater treatment. The monoliths comprise 3D porous structures that will selectively remove radionuclides in an engineered form that can be tailored to various sizes and shapes as required for any column system and can even be made with fine-grained powders unsuitable for normal gravity flow column use. 3D-printed monoliths of zeolites chabazite and 4A were made, characterized, and evaluated for their ion exchange capacities for cesium and strontium under static conditions. The 3D-printed monoliths with 50 wt% zeolite loadings exhibit Cs and Sr uptake with an equivalent ion-capacity as their pristine powders. These monoliths retain their porosity, shape and mechanical integrity in aqueous media, providing a great potential for use to not only remove radionuclides from nuclear wastewater, but more widely in other aqueous separation-based applications and processes.

3D-printed monoliths of zeolites chabazite and 4A were made, characterized, and shown effective for removing strontium and caesium from water.     

Fetal cardiomyopathy--in utero evaluation and clinical significance

OBJECTIVE: To describe the prenatal diagnosis and outcome of fetal cardiomyopathy (CM). METHODS: The charts, photographs and videotapes of all fetuses with CM, who were assessed during pregnancy at two referral centers, were reviewed. RESULTS: The diagnosis of CM was established in 12 fetuses. All had structurally normal hearts, and all cases were diagnosed after 23 weeks of gestation, following normal early fetal echocardiogram. Three clusters of fetal CM appeared: Familial--two sib fetuses of a mother, who is a second generation of CM. Both had dilated CM and pathological findings were consistent with the diagnosis of endocardial fibroelastosis. Secondary--CM that was induced by another factor. Idiopathic--six cases of CM without an underlying specific etiology. Three women elected to terminate their pregnancy. Among the nine who delivered, four had a favorable outcome with normal cardiac function at the age of 1 month, in which three belonged to the secondary category, and five cases were complicated by fetal/infant death. CONCLUSIONS: CM may develop during fetal life and might be diagnosed by prenatal echocardiography. Normal cardiac findings in a midtrimester fetus do not exclude subsequent development of CM. Detailed prenatal sonographic examination may aid in determining the neonatal outcome.     

Staging and managing patients with acromegaly in clinical practice: baseline data from the SAGIT® validation study

Pituitary - The SAGIT® instrument, designed to assist clinicians to stage acromegaly, assess treatment response and adapt patient management, was well received by endocrinologists in a pilot...     

Interatrial blocks. A separate entity from left atrial enlargement: a consensus report

Impaired interatrial conduction or interatrial block is well documented but is not described as an individual electrocardiographic (ECG) pattern in most of ECG books, although the term atrial abnormalities to encompass both concepts, left atrial enlargement (LAE) and interatrial block, has been coined. In fact, LAE and interatrial block are often associated, similarly to what happens with ventricular enlargement and ventricular block. The interatrial blocks, that is, the presence of delay of conduction between the right and left atria, are the most frequent atrial blocks. These may be of first degree (P-wave duration >120 milliseconds), third degree (longer P wave with biphasic [±] morphology in inferior leads), and second degree when these patterns appear transiently in the same ECG recording (atrial aberrancy). There are evidences that these electrocardiographic P-wave patterns are due to a block because they may (a) appear transiently, (b) be without associated atrial enlargement, and (c) may be reproduced experimentally. The presence of interatrial blocks may be seen in the absence of atrial enlargement but often are present in case of LAE. The most important clinical implications of interatrial block are the following: (a) the first degree interatrial blocks are very common, and their relation with atrial fibrillation and an increased risk for global and cardiovascular mortality has been demonstrated; (b) the third degree interatrial blocks are less frequent but are strong markers of LAE and paroxysmal supraventricular tachyarrhythmias. Their presence has been considered a true arrhythmological syndrome.