Apocrine Metaplasia Found at MR Biopsy: Is There Something to be Learned?

The purpose of this study was to determine (a) the frequency of apocrine metaplasia (ApoM) found on MR core biopsy of suspicious findings, and (b) to determine if there are specific MR imaging features that might obviate the need for biopsy. This HIPAA‐compliant retrospective study was performed under IRB exemption for quality assurance studies. Patient demographics, MR imaging features, and pathology were reviewed. Breast lesions which underwent MR‐guided biopsy, yielding ApoM on pathology analysis were included. Retrospective review of MR imaging features of these lesions was performed by two radiologists blinded to pathology results except for the presence of ApoM. Imaging features on MR assessed included location, size, morphology, T1 and T2 signals, and enhancement kinetics. Full pathology results were subsequently reviewed during data analysis. The pathology slides and imaging was subsequently reviewed by two fellowship trained radiologists and a breast pathologist to categorize the finding of ApoM into target lesion (imaging corresponds to size of lesion on pathology) versus incidental lesion. Target lesion characteristics were assessed to determine specific MRI features of ApoM. Between January 2011 to November 2012, 155 distinct breast lesions suspicious for malignancy successfully underwent MR‐guided biopsy. Of the 155 lesions biopsied, 123 (79%) were benign and 32 (21%) were malignant. Of the 123 benign biopsies, ApoM was found in 57 (46%), of which 35 (61%) had no associated atypia and 22 (39%) had associated atypia. Of the 32 malignant biopsies, three (9%) had associated ApoM (DCIS in two cases and DCIS/LCIS in one case). Of the 60 cases with ApoM, only 11 (18.3%) were target lesions and 49 were incidental lesions (81.7%). Of the 60 cases with ApoM, 35 (58%) were masses (average size 0.8 cm for both with or without atypia) and 25 (42%) were nonmass enhancement (NME) (average size 2.1 cm with and 1.0 cm without atypia). Only five (14%) of 35 masses demonstrated spiculated margins, of which four were associated with atypia (80%). Of 22 lesions with atypia or other high‐risk lesion, 14 (64%) were masses, most commonly with irregular margins (64%). Of the 12 T2 hyperintense lesions, only two (1.7)% had associated atypia or high‐risk lesion, and none were associated with malignancy. Of the 11 target lesions, seven were T2 hyperintense. Enhancement kinetics were variable: 30 (50%) showed mixed persistent and plateau kinetics, eight (13%) persistent delayed enhancement, 10 (17%) plateau kinetics, four (7%) washout kinetics, and eight (13%) were below threshold for kinetic analysis. ApoM is a common benign pathologic result at MR‐guided core biopsy for both masses and NME accounting for 39% of all biopsy results in this series. Although there is considerable variability in imaging characteristics on MR, our results suggest biopsy may be safely obviated for lesions that are subcentimeter T2 hyperintense areas of NME and short term follow‐up imaging may be a reasonable alternative for these lesions.     

Homocysteine lowering and cardiovascular disease risk: lost in translation

Studies of the general population have suggested that high homocysteine levels are associated with cardiovascular morbidity and mortality. In chronic kidney disease, homocysteine levels rise, and cardiovascular risk increases with declining kidney function. While some studies in this population have found an association between elevated homocysteine and cardiovascular risk, others have noted that this association is largely attenuated by adjustment for kidney function, and several studies of patients with kidney failure have found that lower homocysteine levels predict mortality. Homocysteine levels can be lowered with folate, vitamin B6 and vitamin B12. Three large, randomized, controlled trials of patients with pre-existing cardiovascular disease and two smaller, randomized, controlled trials of patients with kidney failure failed to detect any cardiovascular benefit from homocysteine-lowering vitamins. Several more interventional trials are ongoing, but the available data thus far do not support screening for or treatment of hyperhomocysteinemia.     

Characterization of somatostatin receptor subtype-specific regulation of insulin and glucagon secretion: an in vitro study on isolated human pancreatic islets

INTRODUCTION: Pancreatic A- and B-cells express somatostatin receptors (SSTRs). Five pharmacologically distinct SSTR subtypes are known (SSTR1-SSTR5). In rodents, SSTR2 inhibits glucagon secretion, whereas SSTR5 suppresses the release of insulin. Human pancreatic A- and B-cells express SSTR1-3 and SSTR5; however, their contribution to the regulation of glucagon and insulin secretion is not well known. AIM OF THE STUDY: The goal of this study was to characterize the role of individual SSTR subtypes in regulating human glucagon and insulin secretion in vitro. METHODS: Human pancreatic islets were isolated from healthy donors and incubated with somatostatin, SSTR1-3-selective and SSTR5-selective agonists, or an SSTR2-selective antagonist (DC-41-33). Stimulation of insulin secretion was induced by glucose (10, 20 mm) alone or in combination with 10 nm exendin-4 or 10 mm L-arginine. Glucagon secretion was induced by 20 mm L-arginine. Basal secretion of insulin and glucagon was measured at 2.8 or 3.3 mm glucose. RESULTS: SSTR1-, SSTR2-, and SSTR5-selective agonists inhibited insulin secretion with the following order of potency: SSTR2 (EC50, 0.08 nm) > SSTR5 (EC50, 5.3 nm) > SSTR1 (EC50, 35 nm). Glucagon secretion was inhibited by SSTR-selective agonists with the following order of potency: SSTR2 (EC50, 0.05 nm) > SSTR1 (EC50, 1.8 nm) > SSTR5 (EC50, 28 nm). DC-41-33 dose-dependently reversed the effects of the SSTR2-selective agonist on insulin and glucagon secretion. CONCLUSION: Our study demonstrates that SSTR2-agonist is the most potent inhibitor of insulin and glucagon secretion from isolated human pancreatic islets. Furthermore, we identify SSTR1- and SSTR5-selective agonists as additional inhibitors of insulin and glucagon secretion from human pancreas.     

Leukocytosis and adverse hospital outcomes after acute myocardial infarction

An elevated white blood cell (WBC) count at the time of hospital presentation is associated with increased mortality after acute myocardial infarction (AMI). The association between WBC count and the development of clinically significant complications of AMI and death during hospitalization for AMI is, however, less clear. The objectives of this observational study were to examine the association between baseline WBC count, the development of heart failure, cardiogenic shock, and death during hospitalization for AMI from a more generalizable community-wide perspective. The study sample consisted of adult residents of all ages from the Worcester, Massachusetts, metropolitan area (1990 census estimate 437,000) hospitalized with confirmed AMI at all greater Worcester medical centers. The study population consisted of 3,796 men and 2,734 women of all ages hospitalized with validated AMI, in 12 annual periods between 1986 and 1999, aggregated into quintiles based on WBC count obtained at the time of hospital admission. In multivariable-adjusted regression analyses controlling for potentially confounding demographic and clinical factors, patients in the uppermost quintiles of WBC count were at increased risk for heart failure (odds ratio [OR] 2.77, 95% confidence interval [CI] 2.33 to 3.31), cardiogenic shock (OR 2.82, 95% CI 2.05 to 3.87), and hospital death (OR 2.14, 95% CI 1.66 to 2.76). The results of our large observational study suggest that the peripheral total leukocyte count is strongly associated with the development of heart failure, cardiogenic shock, and death during hospitalization for AMI. These findings suggest that the WBC count should be considered an important prognostic factor associated with adverse hospital outcomes in patients with AMI.     

Pulse oximetry in supportive and palliative care

Pulse oximetry is a valuable, non-invasive method used for estimating oxyhaemoglobin saturation. It can give a bedside indication of the oxygenation and thus provide a valuable insight into the cause of breathlessness. Its use can help palliative care teams to determine the need to prescribe or to withhold oxygen therapy. The technology is well established and relatively inexpensive. Factors that influence readings include low perfusion states at the end of life. With a thorough understanding of its uses and limitations, pulse oximetry can assist multi-disciplinary teams in providing better care to ill patients in the palliative care setting.     

Concurrent validity of inclinometer measures of scapular and clavicular positions in arm elevation

Objective: To assess concurrent validity, between and within-day reliability of scapular and clavicular digital inclinometer measures. Design: Test–retest and concurrent validity. Setting: Laboratory. Participants: Twenty-three participants with and without shoulder symptoms. Main Outcome Measures: Static positions of scapular upward rotation, anterior/posterior tilting and clavicular elevation were measured between days with an inclinometer and compared to a 3-dimensional electromagnetic tracking system in different positions of sagittal plane humeral elevation (neutral, 30°, 60°, 90°, 120°). The two methods were compared using a two-way Analysis of Variance. Linear regressions at each arm position were also performed to further assess concurrent validity. Results: Between-day reliability demonstrated Intraclass Correlation Coefficients ≥ 0.50 for all comparisons. There were statistically significant differences between methods or interactions of method and arm position for clavicle elevation (p = 0.004, maximum offset between methods 7.7º in the neutral position), and scapular upward rotation (p = 0.001). For scapular upward rotation, the maximum difference between methods was less than 2° across all humeral positions. Clavicle elevation (r = 0.67–0.82) and scapular upward rotation (r = 0.57–0.81) demonstrated higher correlations between measurement methods than scapular anterior/posterior tilt (r = 0.10–0.67). Conclusions: Concurrent validity in assessing scapular upward rotation and clavicle elevation with an inclinometer was shown when compared with electromagnetic tracking. However, the inclinometer method may not have adequate concurrent validity to clinically measure scapular anterior/posterior tilting.     

Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety

Aging of skin is an intricate biological process consisting of two types. While intrinsic or chronological aging is an inevitable process, photoaging involves the premature aging of skin occurring due to cumulative exposure to ultraviolet radiation. Chronological and photoaging both have clinically differentiable manifestations. Various natural and synthetic retinoids have been explored for the treatment of aging and many of them have shown histological and clinical improvement, but most of the studies have been carried out in patients presenting with photoaged skin. Amongst the retinoids, tretinoin possibly is the most potent and certainly the most widely investigated retinoid for photoaging therapy. Although retinoids show promise in the treatment of skin aging, irritant reactions such as burning, scaling or dermatitis associated with retinoid therapy limit their acceptance by patients. This problem is more prominent with tretinoin and tazarotene whereas other retinoids mainly represented by retinaldehyde and retinol are considerably less irritating. In order to minimize these side effects, various novel drug delivery systems have been developed. In particular, nanoparticles have shown a good potential in improving the stability, tolerability and efficacy of retinoids like tretinoin and retinol. However, more elaborate clinical studies are required to confirm their advantage in the delivery of topical retinoids.