Point shear wave elastography method for assessing liver stiffness

AIM:To estimate the validity of the point shear-wave elastography method by evaluating its reproducibility and accuracy for assessing liver stiffness.METHODS:This was a single-center,cross-sectional study.Consecutive patients with chronic viral hepatitis scheduled for liver biopsy(LB)(Group 1)and healthy volunteers(Group 2)were studied.In each subject 10 consecutive point shear-wave elastography(PSWE)measurements were performed using the iU22 ultrasound system(Philips Medical Systems,Bothell,WA,United States).Patients in Group 1 underwent PSWE,transient elastography(TE)using FibroScan(Echosens,Paris,France)and ultrasound-assisted LB.For the assessment of PSWE reproducibility two expert raters(rater 1 and rater 2)independently performed the examinations.The performance of PSWE was compared to that of TE using LB as a reference standard.Fibrosis was staged according to the METAVIR scoring system.Receiver operating characteristic curve analyses were performed to calculate the area under the receiver operating characteristic curve(AUC)for F≥2,F≥3and F=4.The intraobserver and interobserver reproducibility of PSWE were assessed by calculating Lin’s concordance correlation coefficient.RESULTS:To assess the performance of PSWE,134consecutive patients in Group 1 were studied.The median values of PSWE and TE(in kilopascals)were 4.7(IQR=3.8-5.4)and 5.5(IQR=4.7-6.5),respectively,in patients at the F0-F1 stage and 3.5(IQR=3.2-4.0)and 4.4(IQR=3.5-4.9),respectively,in the healthy volunteers in Group 2(P<10-5).In the univariate analysis,the PSWE and TE values showed a high correlation with the fibrosis stage;low correlations with the degree of necroinflammation,aspartate aminotransferase and gamma-glutamyl transferase(GGT);and a moderate negative correlation with the platelet count.A multiple regression analysis confirmed the correlations of both PSWE and TE with fibrosis stage and GGT but not with any other variables.The following AUC values were found:0.80(0.71-0.87)for PSWE and 0.82(0.73-0.89)for TE(P=0.42);0.88(0.80-0.94)for PSWE and 0.95(0.88-0.98)for TE(P=0.06);and 0.95(0.89-0.99)for PSWE and 0.92(0.85-0.97)for TE(P=0.30)for F≥2,F≥3 and F=4,respectively.To assess PSWE reproducibility,116 subjects were studied,including 47consecutive patients scheduled for LB(Group 1)and 69 consecutive healthy volunteers(Group 2).The intraobserver agreement ranged from 0.83(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 1 and from 0.84(95%CI:0.79-0.88)to 0.96(95%CI:0.95-0.97)for rater 2.The interobserver agreement yielded values from0.83(95%CI:0.78-0.88)to 0.93(95%CI:0.91-0.95).CONCLUSION:PSWE is a reproducible method for assessing liver stiffness,and it compares with TE.Compared with patients with nonsignificant fibrosis,healthy volunteers showed significantly lower values.     

Repeat Use of Post-exposure Prophylaxis for HIV Among Nairobi-Based Female Sex Workers Following Sexual Exposure

As ART-based prevention becomes available, effectively targeting these interventions to key populations such as female sex workers (FSW) will be critical. In this study we analyze patterns of repeated post-exposure prophylaxis (PEP) access in the context of a large FSW program in Nairobi. During close to 6000 person-years of follow-up, 20 % of participants (n = 1119) requested PEP at least once and 3.7 % requested PEP more than once. Repeat PEP users were younger, had a higher casual partner volume, and were more likely to use condoms with casual and regular partners, have a regular partner, and test for HIV prior to enrolment. Barriers to PEP included stigma, side effects, and lack of knowledge, suggesting repeated promotion may be required for higher rates of uptake. A small subset of FSW, potentially those with heightened risk perception, showed a higher frequency of PEP use; these individuals may be most amenable to rollout of pre-exposure prophylaxis.     

The effects of periradicular inflamation and infection on a primary tooth and permanent successor

Primary teeth and the permanent successors must be understood as interdependent units, where each one of them interacts with and depends on each other. Pulpal inflammation/infection of a primary tooth and the spread of this condition over the periradicular tissues can lead to alterations in the dental germ of the permanent successor and to the surrounding structures if no therapy is done, i.e. endodontics or extraction. This work will present cases of permanent teeth that showed alteration in eruption and / or in development, as a consequence of inflammation / infection of the preceding primary teeth, such as: hypoplasia, morphological alteration on the dental crown or total arrest of. radicular formation. The teeth analysed in this study belong to patients who attended the Universidade Federal de Santa Catarina Children's Dentistry Clinic. The earlier these lesions are diagnosed, the less were the destructive effects and the consequences on the primary tooth/permanent germ unit.     

Valuation of exfoliative cytology as prediction factor in oral mucosa lesions

The aim of this study was immunolabeling oncoproteins Ck14, p53, p21 and Bcl-2 in order to evaluate their expression in premalignant and malignant stomatological lesions in oral epithelial, and to compare this expression with exfoliative cytology alterations in the same patients. It was studied biopsies and cytologies of 13 subjects with oral lichen planus, with or without Human Papilloma Virus (HPV), leukoplakia and squamous cell carcinoma clinically diagnosed and confirmed by anatomopathological studies. The oral lichen planus lesion presented binuclei orange cells; and in leukoplakia lesions only orange stained was observed; meanwhile koilocytes, inflammatory cells, enlarge nuclear volume and pathogenic microorganisms were observed in the HPV infections and squamous cells carcinoma (SCC). The Ck14, p53, p21 and Bcl-2 proteins were found modified in the leukoplakia, oral lichen planus and cancer. Cytological alterations and positive immunolabeling or over-expression of Ck14 cytokeratine in the upper epithelial stratus should be indicator of malignant transformations as doing subsequence exams.     

Reference charts for weight gain and body mass index during pregnancy obtained from a healthy cohort

Objective. To create reference charts for weight gain and body mass index (BMI) in pregnancy derived from longitudinal data obtained in a representative sample of the Argentinean population.

Methods. A prospective cohort of 1439 healthy pregnant women was selected from antenatal clinics in seven different urban regions in Argentina. Serial anthropometric measurements were made at weeks 12, 16, 20, 24, 28, 32, 36 and in the last pre-natal control. Centile curves of body weight and BMI by gestational age were developed using the LMS method.

Results. Mean weight gain at 38 weeks of gestation was 11.9 ± 4.4 kg. There were no differences in total weight gain between women who enter pregnancy with low, normal or overweight; only those women with a pre-pregnancy BMI in the range of obesity showed a significantly lower weight gain (10.2 ± 4.8 kg). At 12 weeks of pregnancy, BMI values of the 10th, 50th and 90th centiles were 19.3, 22.8 and 29.0, and at 38 weeks these values were 23.3, 27.4 and 33.8, respectively.

Conclusion. This BMI for gestational age chart, based on women who delivered normal birth weight infants and processed with modern statistical methods, represents an improvement in pre-natal care monitoring.     

Ultrasound point shear wave elastography assessment of liver and spleen stiffness: effect of training on repeatability of measurements

Objectives

To evaluate reproducibility of measurements of spleen stiffness (SS) and liver stiffness (LS) at several sites by using point shear wave elastography (pSWE) and to investigate any training effect.

Methods

Healthy volunteers were consecutively enrolled. Measurements of SS and LS were performed by an expert (observer 1) and a novice (observer 2) at three different sites of liver and spleen. To assess the effect of training the study was conducted in two periods (period 1 and period 2). Concordance correlation coefficient was used to assess intra-observer and inter-observer reproducibility.

Results

A total of 92 subjects (67 men and 25 women) were enrolled in the study. Both intra-observer and inter-observer agreement were higher for the liver than for the spleen. Overall, the highest intra-observer and inter-observer agreement were obtained for the assessment of LS through intercostal space, and for measurements at this site there was a significantly better performance of observer 2 after the training period. For both observers, training improved the repeatability of SS measurements at all sites. A good intra-observer agreement was obtained only for measurements at the spleen lower pole.

Conclusions

The results of this study show that a learning curve in pSWE acquisition should be taken into account both for SS and LS measurements.

Key Points

? Reproducibility of SS measurements depends on the expertise of the operator. ? To achieve good reproducibility between measurements a training period is required. ? A learning curve in pSWE acquisition should be taken into account. ? SS measurements are less reproducible than LS measurements.     

Metabolic differences in breast cancer stem cells and differentiated progeny

In general, tumor cells display a more glycolytic phenotype compared to the corresponding normal tissue. However, it is becoming increasingly clear that tumors are composed of a heterogeneous population of cells. Breast cancers are organized in a hierarchical manner, with the breast cancer stem cells (BCSCs) at the top of the hierarchy. Here, we investigate the metabolic phenotype of BCSCs and their differentiated progeny. In addition, we determine the effect of radiation on the metabolic state of these two cell populations. Luminal, basal, and claudin-low breast cancer cell lines were propagated as mammospheres enriched in BCSCs. Lactate production, glucose consumption, and ATP content were compared with differentiated cultures. A metabolic flux analyzer was used to determine the oxygen consumption, extracellular acidification rates, maximal mitochondria capacity, and mitochondrial proton leak. The effect of radiation treatment of the metabolic phenotype of each cell population was also determined. BCSCs consume more glucose, produce less lactate, and have higher ATP content compared to their differentiated progeny. BCSCs have higher maximum mitochondrial capacity and mitochondrial proton leak compared to their differentiated progeny. Radiation treatment enhances the higher energetic state of the BCSCs, while decreasing mitochondrial proton leak. Our study indicated that breast cancer cells are heterogeneous in their metabolic phenotypes and BCSCs reside in a distinct metabolic state compared to their differentiated progeny. BCSCs display a reliance on oxidative phosphorylation, while the more differentiated progeny displays a more glycolytic phenotype. Radiation treatment affects the metabolic state of BCSCs. We conclude that interfering with the metabolic requirements of BCSCs may prevent radiation-induced reprogramming of breast cancer cells during radiation therapy, thus improving treatment outcome.