K.A. Chun

Antimicrobials from human skin commensal bacteria protect against Staphylococcus aureus and are deficient in atopic dermatitis

Commensal skin bacteria produce previously unknown antimicrobial peptides that can inhibit Staphylococcus aureus colonization of atopic dermatitis subjects. Bacterial biological warfare in atopic dermatitis Normal human skin is colonized by a variety of bacteria, which typically do not perturb the host. However, Staphylococcus aureus is known to aggravate symptoms of atopic dermatitis. Nakatsuji et al. report that other strains of Staphylococcus residing on the skin of healthy individuals produce a novel antimicrobial peptide that can inhibit S. aureus growth. Colonization of pigskin or mice with these protective commensals reduced S. aureus replication. Autologous bacterial transplant in a small number of atopic dermatitis patients drastically reduced S. aureus skin burden. This commensal skin transplant is already approved by the U.S. Food and Drug Administration, with a clinical trial underway. The microbiome can promote or disrupt human health by influencing both adaptive and innate immune functions. We tested whether bacteria that normally reside on human skin participate in host defense by killing Staphylococcus aureus, a pathogen commonly found in patients with atopic dermatitis (AD) and an important factor that exacerbates this disease. High-throughput screening for antimicrobial activity against S. aureus was performed on isolates of coagulase-negative Staphylococcus (CoNS) collected from the skin of healthy and AD subjects. CoNS strains with antimicrobial activity were common on the normal population but rare on AD subjects. A low frequency of strains with antimicrobial activity correlated with colonization by S. aureus. The antimicrobial activity was identified as previously unknown antimicrobial peptides (AMPs) produced by CoNS species including Staphylococcus epidermidis and Staphylococcus hominis. These AMPs were strain-specific, highly potent, selectively killed S. aureus, and synergized with the human AMP LL-37. Application of these CoNS strains to mice confirmed their defense function in vivo relative to application of nonactive strains. Strikingly, reintroduction of antimicrobial CoNS strains to human subjects with AD decreased colonization by S. aureus. These findings show how commensal skin bacteria protect against pathogens and demonstrate how dysbiosis of the skin microbiome can lead to disease.

Interobserver Variability in the Assessment of CT Imaging Features of Traumatic Brain Injury

The goal of our study was to determine the interobserver variability between observers with different backgrounds and experience when interpreting computed tomography (CT) imaging features of traumatic brain injury (TBI). We retrospectively identified a consecutive series of 50 adult patients admitted at our institution with a suspicion of TBI, and displaying a Glasgow Coma Scale score < or =12. Noncontrast CT (NCT) studies were anonymized and sent to five reviewers with different backgrounds and levels of experience, who independently reviewed each NCT scan. Each reviewer assessed multiple CT imaging features of TBI and assigned every NCT scan a Marshall and a Rotterdam grading score. The interobserver agreement and coefficient of variation were calculated for individual CT imaging features of TBI as well as for the two scores. Our results indicated that the imaging review by both neuroradiologists and neurosurgeons were consistent with each other. The kappa coefficient of agreement for all CT characteristics showed no significant difference in interpretation between the neurosurgeons and neuroradiologists. The average Bland and Altman coefficients of variation for the Marshall and Rotterdam classification systems were 12.7% and 21.9%, respectively, which indicates acceptable agreement among all five reviewers. In conclusion, there is good interobserver reproducibility between neuroradiologists and neurosurgeons in the interpretation of CT imaging features of TBI and calculation of Marshall and Rotterdam scores.

The Triple Rule-Out for Acute Ischemic Stroke: Imaging the Brain, Carotid Arteries, Aorta, and Heart

BACKGROUND AND PURPOSE: Ischemic stroke is commonly embolic, either from carotid atherosclerosis or from cardiac origin. These potential sources of emboli need to be investigated to accurately prescribe secondary stroke prevention. Moreover, the mortality in ischemic stroke patients due to ischemic heart disease is greater than that of age-matched controls, thus making evaluation for coronary artery disease important in this patient population. The purpose of this study was to evaluate the image quality of a comprehensive CTA protocol in patients with acute stroke that expands the standard CTA coverage to include all 4 chambers of the heart and the coronary arteries. MATERIALS AND METHODS: One hundred twenty patients consecutively admitted to the emergency department with suspected cerebrovascular ischemia undergoing standard-of-care CTA were prospectively enrolled in our study. We used an original tailored acquisition protocol using a 64-section CT scanner, consisting of a dual-phase intravenous injection of iodinated contrast and saline flush, in conjunction with a dual-phase CT acquisition, ascending from the top of the aortic arch to the vertex of the head, then descending from the top of the aortic arch to the diaphragm. No beta blockers were administered. The image quality, attenuation, and CNRs of the carotid, aortic, vertebral, and coronary arteries were assessed. RESULTS: Carotid, aorta, and vertebral artery image quality was 100% diagnostic (rated good or excellent) in all patients. Coronary artery image quality was diagnostic in 58% of RCA segments, 73% of LAD segments, and 63% of LCX segments. When we considered proximal segments only, the diagnostic quality rose to 71% in the RCA, 83% in the LAD, and 74% in the LCX. CONCLUSIONS: Our stroke protocol achieved excellent opacification of the left heart chambers, the cervical arteries, and each coronary artery, in addition to adequate carotid and coronary artery image quality.

Carotid Atherosclerosis Does Not Predict Coronary, Vertebral, or Aortic Atherosclerosis in Patients With Acute Stroke Symptoms

Background and Purpose— The purpose of this study was to determine whether significant atherosclerotic disease in the carotid arteries predicts significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. Methods— Atherosclerotic disease was imaged using CT angiography in a prospective study of 120 consecutive patients undergoing emergent CT evaluation for symptoms of stroke. Using a comprehensive CT angiography protocol that captured the carotid arteries, coronary arteries, vertebral arteries, and aorta, we evaluated these arteries for the presence and severity of atherosclerotic disease. Significant atherosclerotic disease was defined as >50% stenosis in the carotid, coronary, and vertebral arteries, or ≥4 mm thickness and encroaching in the aorta. Presence of any and significant atherosclerotic disease was compared in the different types of arteries assessed. Results— Of these 120 patients, 79 had CT angiography examinations of adequate image quality and were evaluated in this study. Of these 79 patients, 33 had significant atherosclerotic disease. In 26 of these 33 patients (79%), significant disease was isolated to 1 type of artery, most often to the coronary arteries (N=14; 54%). Nonsignificant atherosclerotic disease was more systemic and involved multiple arteries. Conclusions— Significant atherosclerotic disease in the carotid arteries does not predict significant atherosclerotic disease in the coronary arteries, vertebral arteries, or aorta in patients with symptoms of acute ischemic stroke. Significant atherosclerotic disease is most often isolated to 1 type of artery in these patients, whereas nonsignificant atherosclerotic disease tends to be more systemic.

Basal Cell Carcinoma of the Nipple-Areolar Complex

Basal cell carcinoma (BCC) of the areola and nipple has been described in 35 men (median onset age, 61 years) and 20 women (median onset age, 66 years). The tumor occurred more frequently on the left side (54.9%) than the right side (45.1%). BCC of the nipple-areolar complex (NAC) is commonly presented as scaly or with ulcerated plaques and nodules. The pathologic type of BCC was most commonly nodular (42.9%) or superficial (30.9%). Although BCC of the NAC are frequently associated with a nonaggressive histologic subtype, they have been considered to behave more aggressively than BCCs at other anatomical sites. Complete excision of the BCC is the treatment of choice. Successful treatment of the primary tumor is rarely followed by cancer recurrence.

Demographics of carotid atherosclerotic plaque features imaged by computed tomography.

OBJECTIVES This was a prospective, cross-sectional study to evaluate the risk factors and symptoms associated with specific carotid wall and atherosclerotic plaque features as seen on computed tomography-angiography (CTA) studies. MATERIALS AND METHODS A total of 120 consecutive consenting patients admitted to the emergency department with suspected cerebrovascular ischemia, and receiving standard-of-care CTA of the brain and neck on a 64-slice CT scanner, were prospectively enrolled in the study. The carotid wall features observed on CT were quantitatively analyzed with customized software using different radiodensities for contrast-phase acquisition of the carotids. Clinical datasets, including a complete medical history and examination, were obtained by research physicians or specially trained associates blinded to any findings on CT. Univariate and multivariate analyses were performed to assess the degree of association between clinical indicators and quantitative CT features of carotid atherosclerotic plaques. RESULTS Men tended to have increased carotid lumen (coefficient: 608.7; 95% CI: 356.9-860.6; P<0.001) and wall volumes (209.2; 54.5-364.0; P=0.008), and hypertension was associated with increased wall volume (260.6; 88.7-432.6; P=0.003). Advanced age was associated with increases in maximum wall thickness (0.02; 0.003-0.05; P=0.029), fibrous cap thickness (0.005; 0.001-0.008; P=0.016) and number of calcium voxels (2.7; 1.25-4.2; P<0.001), and the presence of a carotid bruit was associated with carotid stenosis length (21.0; 5.38-37.8; P=0.009). Exercise was inversely related to the number of calcium (-37.1; -71.5 - -2.7; P=0.035) and lipid (-7.9; -15.1 - -0.7; P=0.032) voxels. ACE inhibitor use was associated with fibrous cap thickness (0.1; 0.04-0.23; P=0.005). CONCLUSION Significant associations were found between clinical descriptors and carotid atherosclerotic plaque features as revealed by CT. Future studies are needed to validate our findings, and to continue investigations into whether CT features of carotid plaques can be used as biomarkers to quantify the impact of strategies aiming to correct vascular risk factors.