Pretreatment haemoglobin levels significantly predict the tumour response to primary chemotherapy in human breast cancer

The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l(-1) onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl(-1) (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels </=13 g dl(-1) showed a lower treatment-induced reduction in Ki67 expression (P<0.04) and a higher Ki67 expression at postoperative evaluation (P<0.02) than their counterparts. In conclusion, low Hb levels may negatively influence the response rate of chemotherapy in breast cancer patients. Inhibition of antiproliferative activity could be a possible mechanism

Age and gender specific normal values of left ventricular mass, volume and function for gradient echo magnetic resonance imaging: a cross sectional study

<p>Abstract</p> <p>Background</p> <p>Knowledge about age-specific normal values for left ventricular mass (LVM), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF) by cardiac magnetic resonance imaging (CMR) is of importance to differentiate between health and disease and to assess the severity of disease. The aims of the study were to determine age and gender specific normal reference values and to explore the normal physiological variation of these parameters from adolescence to late adulthood, in a cross sectional study.</p> <p>Methods</p> <p>Gradient echo CMR was performed at 1.5 T in 96 healthy volunteers (11–81 years, 50 male). Gender-specific analysis of parameters was undertaken in both absolute values and adjusted for body surface area (BSA).</p> <p>Results</p> <p>Age and gender specific normal ranges for LV volumes, mass and function are presented from the second through the eighth decade of life. LVM, ESV and EDV rose during adolescence and declined in adulthood. SV and EF decreased with age. Compared to adult females, adult males had higher BSA-adjusted values of EDV (p = 0.006) and ESV (p < 0.001), similar SV (p = 0.51) and lower EF (p = 0.014). No gender differences were seen in the youngest, 11–15 year, age range.</p> <p>Conclusion</p> <p>LV volumes, mass and function vary over a broad age range in healthy individuals. LV volumes and mass both rise in adolescence and decline with age. EF showed a rapid decline in adolescence compared to changes throughout adulthood. These findings demonstrate the need for age and gender specific normal ranges for clinical use.</p

LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association

<p>Abstract</p> <p>Background</p> <p>In patients with severe aortic stenosis (AS), long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR) offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability.</p> <p>Hypothesis</p> <p>We hypothesize that changes in LV structure and function following aortic valve replacement (AVR) are detectable by CMR and once triggered by AVR, continue for an extended period.</p> <p>Methods</p> <p>Tweny-four patients of which ten (67 ± 12 years, 6 female) with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured.</p> <p>Results</p> <p>All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m^<b>2</b>, p < 0.005) and continued trending downwards through 4 years (127 ± 32 g/m^<b>2</b>). Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p < 0.05)) and continued trending upwards, remaining stable through years 1-4 (66 ± 11 vs. 65 ± 9%). LVEDVI, initially high pre-AVR, decreased post-AVR (83 ± 30 to 68 ± 11 ml/m2, p < 0.05) trending even lower by year 4 (66 ± 10 ml/m^<b>2</b>). LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p < 0.05) continuing to increase non-significantly through 4 years (49 ± 14 ml) with these LV metrics paralleling improvements in NYHA. However, LVmass/volume, a 3D measure of LV geometry, remained unchanged over 4 years.</p> <p>Conclusion</p> <p>After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.</p

Reduced global longitudinal strain in association to increased left ventricular mass in patients with aortic valve stenosis and normal ejection fraction: a hybrid study combining echocardiography and magnetic resonance imaging

<p>Abstract</p> <p>Background</p> <p>Increased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF.</p> <p>Methods</p> <p>50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area.</p> <p>Results</p> <p>The total group of patients with AST showed a GLS of -15,2 ± 3,6% while the control group reached -19,5 ± 2,7% (p < 0,001). By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 ± 2,6%, -13,2 ± 3,8% and -12,4 ± 2,9%, respectively (p = 0,001), where LVMi and GLS showed a significant correlation (r = 0,6, p < 0,001).</p> <p>Conclusions</p> <p>In conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF.</p

Universal Plant DNA Barcode Loci May Not Work in Complex Groups: A Case Study with Indian Berberis Species

BACKGROUND: The concept of DNA barcoding for species identification has gained considerable momentum in animals because of fairly successful species identification using cytochrome oxidase I (COI). In plants, matK and rbcL have been proposed as standard barcodes. However, barcoding in complex genera is a challenging task. METHODOLOGY AND PRINCIPAL FINDINGS: We investigated the species discriminatory power of four reportedly most promising plant DNA barcoding loci (one from nuclear genome--ITS, and three from plastid genome--trnH-psbA, rbcL and matK) in species of Indian Berberis L. (Berberidaceae) and two other genera, Ficus L. (Moraceae) and Gossypium L. (Malvaceae). Berberis species were delineated using morphological characters. These characters resulted in a well resolved species tree. Applying both nucleotide distance and nucleotide character-based approaches, we found that none of the loci, either singly or in combinations, could discriminate the species of Berberis. ITS resolved all the tested species of Ficus and Gossypium and trnH-psbA resolved 82% of the tested species in Ficus. The highly regarded matK and rbcL could not resolve all the species. Finally, we employed amplified fragment length polymorphism test in species of Berberis to determine their relationships. Using ten primer pair combinations in AFLP, the data demonstrated incomplete species resolution. Further, AFLP analysis showed that there was a tendency of the Berberis accessions to cluster according to their geographic origin rather than species affiliation. CONCLUSIONS/SIGNIFICANCE: We reconfirm the earlier reports that the concept of universal barcode in plants may not work in a number of genera. Our results also suggest that the matK and rbcL, recommended as universal barcode loci for plants, may not work in all the genera of land plants. Morphological, geographical and molecular data analyses of Indian species of Berberis suggest probable reticulate evolution and thus barcode markers may not work in this case

Methods of estimation of mitral valve regurgitation for the cardiac surgeon

Mitral valve regurgitation is a relatively common and important heart valve lesion in clinical practice and adequate assessment is fundamental to decision on management, repair or replacement. Disease localised to the posterior mitral valve leaflet or focal involvement of the anterior mitral valve leaflet is most amenable to mitral valve repair, whereas patients with extensive involvement of the anterior leaflet or incomplete closure of the valve are more suitable for valve replacement. Echocardiography is the recognized investigation of choice for heart valve disease evaluation and assessment. However, the technique is depended on operator experience and on patient's hemodynamic profile, and may not always give optimal diagnostic views of mitral valve dysfunction. Cardiac catheterization is related to common complications of an interventional procedure and needs a hemodynamic laboratory. Cardiac magnetic resonance (MRI) seems to be a useful tool which gives details about mitral valve anatomy, precise point of valve damage, as well as the quantity of regurgitation. Finally, despite of its higher cost, cardiac MRI using cine images with optimized spatial and temporal resolution can also resolve mitral valve leaflet structural motion, and can reliably estimate the grade of regurgitation

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly