Rational variety mapping for contrast-enhanced nonlinear unsupervised segmentation of multispectral images of unstained specimen

A methodology is proposed for nonlinear contrast-enhanced unsupervised segmentation of multispectral (color) microscopy images of principally unstained specimens. The methodology exploits spectral diversity and spatial sparseness to find anatomical differences between materials (cells, nuclei, and background) present in the image. It consists of rth-order rational variety mapping (RVM) followed by matrix/tensor factorization. Sparseness constraint implies duality between nonlinear unsupervised segmentation and multiclass pattern assignment problems. Classes not linearly separable in the original input space become separable with high probability in the higher-dimensional mapped space. Hence, RVM mapping has two advantages: it takes implicitly into account nonlinearities present in the image (ie, they are not required to be known) and it increases spectral diversity (ie, contrast) between materials, due to increased dimensionality of the mapped space. This is expected to improve performance of systems for automated classification and analysis of microscopic histopathological images. The methodology was validated using RVM of the second and third orders of the experimental multispectral microscopy images of unstained sciatic nerve fibers (nervus ischiadicus) and of unstained white pulp in the spleen tissue, compared with a manually defined ground truth labeled by two trained pathophysiologists. The methodology can also be useful for additional contrast enhancement of images of stained specimens.     

The Relationship Between Hormone Therapy Use at the Time of Diagnosis of Breast Cancer and Tumor Characteristics

Exposure to postmenopausal hormone therapy (HT) may affect the stage, histological type, and hormone receptor (HR) status of invasive breast cancer at the time of diagnosis. One thousand six hundred eighty-four women with newly diagnosed first invasive breast cancer were recruited to the “MBF Foundation Health and Wellbeing after Breast Cancer Study.” Women using systemic HT estrogen (E) or E combined with progesterone (P) at the time of diagnosis of breast cancer were compared with those not using HT. Breast cancer tumor data were obtained from the Victorian Cancer Registry. Regression analysis was used to determine the associations between HT use or not at the time of diagnosis and tumor histology (ductal vs lobular), stage (I vs II, III, IV), HR status (ER+ or PR+ or both vs ER? or PR?). Of 1,377 women included in the analysis, 226 (16%) were using HT at the time of diagnosis. Of HT users, 20.4% had lobular breast cancer, 50% were stage I, and 85.8% had HR-positive tumors. Of non-users, 13.6% had lobular breast cancer, 48.2% were stage I, and 82.4% had HR-positive tumors. Use of systemic HT was associated with increased odds of having lobular compared with ductal breast cancer (OR?=?1.75, 95% CI?=?1.14–2.69, p?=?0.01). There were no associations between HT use and either breast cancer stage or HR status. Women using systemic HT at the time of diagnosis were more likely to have lobular rather than ductal breast cancer compared with women not on HT.     

Development of psoriasis in IBD patients under TNF-antagonist therapy is associated neither with anti-TNF-antagonist antibodies nor trough levels

Background: The cause of anti-TNF-induced psoriasis is still unknown.

Objective: We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels.

Methods: In this case-control study we identified 23 patients (21 with Crohn’s disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n?=?20), adalimumab (ADA, n?=?2), and certolizumab pegol (CZP, n=?1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis.

Results: Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p?=?0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p?=?0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6?μg/mL [IQR 0.9–5.5] vs. 3.4?μg/mL [IQR 1.4–8.1], p?=?0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies.

Conclusion: Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.     

Induction mortality and resource utilization in children treated for acute myeloid leukemia at free‐standing pediatric hospitals in the United States

BACKGROUND:

Clinical trials in pediatric acute myeloid leukemia (AML) determine induction regimen standards. However, these studies lack the data necessary to evaluate mortality trends over time and differences in resource utilization between induction regimens. Moreover, these trials likely underreport the clinical toxicities experienced by patients.

METHODS:

The Pediatric Health Information System database was used to identify children treated for presumed de novo AML between 1999 and 2010. Induction mortality, risk factors for induction mortality, and resource utilization by induction regimen were estimated using standard frequentist statistics, logistic regression, and Poisson regression, respectively.

RESULTS:

A total of 1686 patients were identified with an overall induction case fatality rate of 5.4% that decreased from 9.8% in 2003 to 2.1% in 2009 (P = .0023). The case fatality rate was 9.0% in the intensively timed DCTER (dexamethasone, cytarabine, thioguanine, etoposide, and rubidomycin [daunomycin]/idarubicin) induction and 3.8% for ADE (cytarabine, daunomycin, and etoposide) induction (adjusted odds ratio = 2.2, 95% confidence interval = 1.1‐4.5). Patients treated with intensively timed DCTER regimens had significantly greater antibiotic, red cell/platelet transfusion, analgesic, vasopressor, renal replacement therapy, and radiographic resource utilization than patients treated with ADE regimens. Resource utilization was substantially higher than reported in published pediatric AML clinical trials.

CONCLUSIONS:

Induction mortality for children with AML decreased significantly as ADE use increased. In addition to higher associated mortality, intensively timed DCTER regimens had a correspondingly higher use of health care resources. Using resource utilization data as a proxy for adverse events, adverse event rates reported on clinical trials substantially underestimated the clinical toxicities of all pediatric AML induction regimens. Cancer 2013. © 2013 American Cancer Society.     

Antioxidant and Physicochemical Properties of Hydrogen Peroxide‐Treated Sugar Beet Dietary Fibre

The aim of the present work was to examine if hydrogen peroxide treatment of sugar beet fibre that aimed at improving its physicochemical properties would impair its antioxidant potential. Three different sugar beet fibres were obtained from sugar beet – non‐treated fibre (NTF) from sugar beet cossettes extracted with sulphurous acid, treated fibre (TF) from NTF treated with hydrogen peroxide in alkaline solution and commercially available Fibrex^®. The antioxidant activity of extractable and non‐extractable fibre fractions in ethanol/water mixture (80:20, v/v) of three fibre samples was estimated. Non‐extractable fractions obtained after alkaline treatment of investigated fibres were much higher in phenolic compounds and possessed higher antioxidant potential than extractable fractions. Ferulic acid was proven to be the dominant phenolic acid. Regarding both extractable and non‐extractable fractions, Fibrex^® had the highest antioxidant activity in chemical tests, while NTF was superior in comparison with TF. Based on the results of Caco‐2 cells‐based test, all non‐extractable fractions possessed potential for reactive oxygen species inhibition. Regarding the extractable fractions, only the TF manifested this effect.Copyright © 2016 John Wiley & Sons, Ltd.     

The impact of continuous positive airway pressure on cardiac mechanics: Findings from a meta‐analysis of echocardiographic studies

Current evidence on the effects of continuous positive airway pressure (CPAP) on cardiac mechanics in patients with obstructive sleep apnea (OSA) is based on a few single studies. The authors investigated this topic through a meta‐analysis of speckle tracking echocardiography (STE) studies that provided data on left ventricular (LV) and right ventricular (RV) mechanics as assessed by global longitudinal strain (GLS). The PubMed, OVID‐MEDLINE, and Cochrane library databases were systematically analyzed to search English‐language review papers published from inception to January 31, 2022. Studies were identified by crossing the following terms: “obstructive sleep apnea”, “sleep quality”, “sleep disordered breathing”, “continuous positive airway pressure therapy”, “noninvasive ventilation”, “left ventricular hypertrophy”, “systolic dysfunction”, “global longitudinal strain”, “left ventricular mechanics”, “right ventricular mechanics”, “echocardiography” and “STE echocardiography”. The meta‐analysis, including a total of 337 patients with OSA from nine studies (follow‐up 2–24 months) showed a significant GLS improvement in both LV and RV after CPAP, standard mean difference (SMD) being 0.51±0.08, CI:0.36–0.66, p = .0001 and 0.28±0.07, CI:0.15–0.42, p = .0001), respectively. Corresponding SMD values for LV ejection fraction (LVEF) and tricuspid annular plane systolic excursion (TAPSE) were 0.20±0.06, CI:0.08–0.33, p = .001 and 0.08±0.06, CI: ‐0.04/0.20, p = .21. Our meta‐analysis suggests that: I) CPAP treatment exerts beneficial effects on biventricular function in patients with OSA; II) the assessment of cardiac mechanics by STE should be routinely recommended for monitoring cardiac function in this setting, due to limitations of conventional echocardiography in evaluating biventricular performance.