- High circulating tumor cell concentrations in a specific subtype of gastric cancer with diffuse bone metastasis at diagnosis. [JOURNAL ARTICLE]
- World J Gastroenterol 2016 Jul 14; 22(26):6083-6088.
To clarify the biological feature contributing to gastric cancer with diffuse bone metastases at diagnosis.The participants visited the Department of Clinical Oncology, Akita University Hospital, from January 2014 to August 2015. The selection criterion for gastric cancer with diffuse bone metastases at diagnosis includes over 29 hot spots of bone scintigraphy. Circulating tumor cell were collected from 20 mL of peripheral venous blood drawn using a CellSearch kit and a CellTracks AutoPrep system by SRL, a clinical laboratory. The endpoints of this study were correlations between circulating tumor cells (CTC) count and therapeutic outcomes.Among 39 patients with gastric cancer, 5 patients met the criterion. The incidence of this subtype was 12.8%. CTC counts ranged from 235 to 6440 cells/7.5 mL of peripheral blood (median of 1724). These values were much higher than common gastric cancers (2 cells). In chemo-sensitive cases, CTC counts decreased within 14 d (median) from 275, 235 and 1724 to 2, 7 and 66, respectively. On the other hand, CTC counts increased after treatment failure or insensitive case from 2, 7 and 6440 to 787, 513 and 7885, respectively. The correlation between CTC count and survival time showed a trend, but did not reach significance (Y = 234.6 - 0.03X, P = 0.085).High CTC count is a biological hallmark of this subtype, and can be used as a direct and definitive indicator of therapeutic outcome.
- Cell-to-cell distances between tumor-infiltrating inflammatory cells have the potential to distinguish functionally active from suppressed inflammatory cells. [JOURNAL ARTICLE]
- Oncoimmunology 2016 May; 5(5):e1127494.
Beyond their mere presence, the distribution pattern of inflammatory cells is of special interest. Our hypothesis was that random distribution may be a clear indicator of being non-functional as a consequence of lack of interaction. Here, we have assessed the implication of cell-to-cell distances among inflammatory cells in anal squamous cell carcinoma and a possible association with survival data. Thirty-eight patients suffering from anal carcinoma were studied using tissue microarrays, double staining immunohistochemistry, whole slide scanning and image analysis software. Therapy consisted of concurrent radiochemotherapy. Numbers of stromal and intraepithelial tumor-infiltrating inflammatory cells (TIC) and the distances between cells were quantified. Double-staining of FoxP3(+) cells with either CD8(+), CD1a(+) or CD20(+) cells was performed. Measured cell-to-cell distances were compared to computer simulated cell-to-cell distances leading to the assumption of non-randomly distributed and therefore functional immune cells. Intraepithelial CD1a(+) and CD20(+) cells were randomly distributed and therefore regarded as non-functional. In contrary, stromal CD20(+) cells had a non-random distribution pattern. A non-random distance between CD20(+) and FoxP3(+) cells was associated with a clearly unfavorable outcome. Measured distances between FoxP3(+) cells were distinctly shorter than expected and indicate a functional active state of the regulatory T cells (Treg). Analysis of cell-to-cell distances between TIC has the potential to distinguish between suppressed non-functional and functionally active inflammatory cells. We conclude that in this tumor model most of the CD1a(+) cells are non-functional as are the intraepithelial CD20(+) cells, while stromal CD20(+) cells and FoxP3(+) cells are functional cells.
- An exploratory investigation of the daily talk time of people with non-fluent aphasia and non-aphasic peers. [JOURNAL ARTICLE]
- Int J Speech Lang Pathol 2016 Jul 28.:1-12.
This paper presents an exploratory investigation of the talk time of people with non-fluent aphasia, as measured by the CommFit™ app. Aims were to compare the talk time of people with aphasia with non-aphasic peers and measures of impairment, activity and participation. The variability of talk time over weeks and days of the week was also investigated.Twelve people with post-stroke, non-fluent aphasia and seven non-aphasic controls measured their talk time using the CommFit™ app for 6 h/day for 14 days.People with aphasia talked for a mean of 4.5 min/h and non-aphasic controls 7.2 min/h, which was not a significant difference (p = 0.056). Talk time of people with aphasia was not significantly correlated with WAB-R AQ or CADL-2 scores, but a moderate-high positive relationship between talk time and SIPSO scores was found (r = 0.648, p = 0.015). Talk time was not significantly different between the first and second weeks of recording for either group, and days of the week were not significantly different except for Saturdays, in which talk time was higher.This study provides some preliminary data on talk time in people with aphasia, suggesting that talk time is an indicator of participation.
- Prevalence and Associated Clinical Characteristics of Exercise-Induced ST-Segment Elevation in Lead aVR. [JOURNAL ARTICLE]
- PLoS One 2016; 11(7):e0160185.
Exercise-induced ST-segment elevation (STE) in lead aVR may be an important indicator of prognostically important coronary artery disease (CAD). However, the prevalence and associated clinical features of exercise-induced STE in lead aVR among consecutive patients referred for exercise stress electrocardiography (ExECG) is unknown.All consecutive patients receiving a Bruce protocol ExECG for the diagnosis of CAD at a tertiary care academic center were included over a two-year period. Clinical characteristics, including results of coronary angiography, were compared between patients with and without exercise-induced STE in lead aVR.Among 2227 patients undergoing ExECG, exercise-induced STE ≥1.0mm in lead aVR occurred in 3.4% of patients. Patients with STE in lead aVR had significantly lower Duke Treadmill Scores (DTS) (-0.5 vs. 7.0, p<0.01) and a higher frequency of positive test results (60.2% vs. 7.3%, p<0.01). Furthermore, patients with STE in lead aVR were more likely to undergo subsequent cardiac catheterization than those without STE in lead aVR (p<0.01, odds ratio = 4.2).Among patients referred for ExECG for suspected CAD, exercise-induced STE in lead aVR was associated with a higher risk DTS, an increased likelihood of a positive ExECG, and referral for subsequent coronary angiography. These results suggest that exercise-induced STE in lead aVR may represent a useful ECG feature among patients undergoing ExECG in the risk stratification of patients.
- Crimean-Congo Hemorrhagic Fever Virus in Bulgaria and Turkey. [JOURNAL ARTICLE]
- Vector Borne Zoonotic Dis 2016 Jul 28.
Infections of humans with the tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) can cause a severe hemorrhagic fever with case fatality rates of up to 80%. Most humans are infected by tick bite, crushing infected ticks by hand or by unprotected contact with blood of viremic mammals. Next to the notified human CCHF cases, the real distribution and the situation in animals in Southeastern Europe are nearly unknown. Since domestic ruminants play a crucial role in the life cycle of the vector ticks and the transmission and amplification of the virus, the antibody prevalence in those animals is a good indicator for the presence of CCHFV in a region. Therefore, the prevalence of CCHFV-specific antibodies was investigated in domestic ruminants of different regions of Bulgaria and Turkey. Sera of 1165 ruminants were tested and a prevalence of up to 90% was identified. The overall prevalence for Bulgaria was 26% and for Turkey 57%. The results highlight the risk of human infections in those regions and the importance of the investigation of the prevalence in animals for identification of risk areas. This article provides a unique overview about published CCHFV antibody prevalence in animals in comparison to human incidences in different areas of Bulgaria and Turkey. Although it will help to complete the understanding of the CCHFV situation in these countries, it also demonstrates the lack of unpublished and published data even in these highly endemic areas.
- Eco-toxicological bioassay of atmospheric fine particulate matter (PM2.5) with Photobacterium Phosphoreum T3. [JOURNAL ARTICLE]
- Ecotoxicol Environ Saf 2016 Jul 25.:226-234.
A bioluminescent bacterium, Photobacterium phosphoreum T3 (PPT3), was used as a bio-indicator for the atmospheric fine particulate matter (PM2.5) to determine the eco-toxicity of PM2.5. The PM2.5 contains toxic chemicals, which reduce light output. The PM2.5 samples were collected in the period from March 2014 to January 2015 in Nanjing and analyzed for the chemical composition versus their eco-toxicity. The eco-toxicological responses of each toxicant were detected in PM2.5 samples with PPT3. The dose-response curves obtained were verified using the Weibull fitting function. According to the measured EC50 values (EC50, the concentration of a toxicant that inhibits 50% of the bioluminescence), the toxicity sequence was: B[a]P>hexa-PCB>tetra-PCB>tri-PCB>Pb(2+)>DEHP>Cu(2+)>DBP>BDE209>Zn(2+)>DMP>DEP, where B[a]P is benzo(a)pyrene, PCB is polychlorinated biphenyl, DEHP is diethylhexyl phthalate, DBP is dibutyl phthalate, BDE209 is decabromodiphenyl ether, DMP is dimethyl phthalate, and DEP is diethyl phthalate. All the PM2.5 samples analyzed proved to be weak toxic for PPT3. The toxicity of PM2.5 was assessed by the dose-addition of organic species and heavy metallic elements existing in PM2.5 with PPT3. The bioluminescence test showed that the metals and organics detected in PM2.5 promoted PM2.5 toxicity. The total detectable organics (denoted by ΣOrs) exhibited slightly higher toxicity than the total metals (denoted by ΣMs). In contrast, the sum of water-soluble ions (denoted by ΣIons) was beneficial to PPT3. The PM2.5 toxicity increased as the PM2.5 trapped more organics or metallic elements from the industrial or densely populated urban areas, where the PM2.5 had a high inhibition rate of bioluminescence for PPT3 in contrast to the residential PM2.5 samples, where the minimum inhibition rate was observed. The toxicity of PM2.5 samples varied with the mass concentrations, chemical constituents, and sampling locations. The chemicals in PM2.5, especially organic species and metallic elements, affected its eco-toxicity. These data provided good understanding of the atmospheric PM2.5 pollution in the large portion of the East China.
- Improved Risk Stratification for Breast Cancer Samples Based on the Expression Ratio of the Estrogen and Progesterone Receptor. [Journal Article]
- Anticancer Res 2016 Aug; 36(8):3855-63.
The receptors for estrogen (ESR1) and progesterone (PGR) are both part of the same signaling pathway and routinely used for breast cancer stratification. We tested the hypothesis if a coordinated analysis could add extra information for prognostic stratification.ESR1 and PGR gene expression was first investigated by quantitative reverse transcription polymerase chain reaction in fresh-frozen invasive ductal breast cancer samples (Hamburg collective, case-control, n=317). Our results were then tested using two datasets generated by different technical approaches: i) a public DNA-chip data set (GSE3494, n=251) and ii) semiquantitative protein expression data based on immunohistochemistry (Stuttgart collective, n=18,528).The PGR/ESR1 gene-expression ratio was a prognostic indicator in those with ESR1/PGR-positive breast cancer (Hamburg collective), with a high PGR/ESR1 expression ratio indicating a favorable outcome. In all three collectives, the PGR/ESR1 mRNA ratio or its protein equivalent was a univariate prognostic factor and also a multivariate prognostic factor in the Hamburg and Stuttgart collectives.Calculation of the PGR/ESR1 gene-expression ratio and its immunohistochemical surrogate could be a useful and simple addition to routine breast cancer diagnostics. A high PGR/ESR1 ratio could be indicative of a favorable clinical outcome.
- Body fatness throughout the life course and the incidence of premenopausal breast cancer. [JOURNAL ARTICLE]
- Int J Epidemiol 2016 Jul 27.
The role of body fatness in the aetiology of breast cancer is complex. We evaluated the independent and synergistic effects of body fatness, at different stages throughout a woman's life course, on premenopausal breast cancer risk.Premenopausal participants of the Nurses' Health Study II (NHSII) were followed from 1991 up to 2009. Body fatness factors including birthweight, somatotype (a 9-level pictogram with level 1 being the leanest) at ages 5 and 10 years and body mass index (BMI) at age 18 were collected at baseline. Current BMI was updated biennially. Multivariate Cox regression models were used to evaluate the association between each body fatness factor as well as cross-classification of all factors and the incidence of breast cancer.Based on 1574 incident premenopausal breast cancer cases and 1 133 893 person-years of follow-up, a lower incidence was associated with lower birthweight: hazard ratio (HR) [95% confidence interval (CI)] = 0.74 (0.58-0.95) for <2.5kg vs 3.9+kg, P for trend < 0.001; higher somatotype at age 5: HR=0.57 (95% CI 0.44-0.73) for 5-9 vs 1, P fortrend < 0.0001]; and at age 10: HR=0.61 (95% CI 0.49-0.75) for 5-9 vs 1, P for trend < 0.0001]; and BMI at age 18: HR=0.67 (95% 0.47-0.95) for ≥ 27.5 kg/m(2) vs < 18.5 kg/m(2), P for trend = 0.009], after adjusting for age and body fatness measures earlier in life and other risk factors, respectively. No significant interaction between body fatness measures was found. Women with the lowest birthweight, the highest somatotype at ages 5 and 10 and the highest BMI at age 18 and currently had a 72% (95% CI 54%-83%) lower incidence of invasive premenopausal breast cancer than women with the opposite extreme of each body fatness indicator.The lowest incidence of premenopausal breast cancer was associated with the lowest birthweight and the highest childhood, adolescent and early adult body fatness.
- Sequential Crohn's Ileitis, Ileosigmoidal Fistula, Segmental Sigmoid Polyposis, and Sigmoid Stricture: The Natural History. [JOURNAL ARTICLE]
- J Clin Gastroenterol 2016 Jul 25.
We have previously recognized segmental sigmoid polyps as an indicator of a fistula from Crohn's ileitis to the sigmoid or the proximal rectum. In the course of this study, we realized that many patients with this fistula had no sigmoid polyps, but the sigmoid was the site of marked inflammation and early or late stricture formation. Furthermore, in some patients with a stricture, the fistula was not recognized until the surgeon (or the pathologist) dissected an inflammatory peri-ileal and/or a perisigmoidal mass.In this study, we have sought to clarify the sequence of events by focusing on the segmental inflammation and the stricturing of the sigmoid so that its significance can be recognized as a local complication of the ileitis and the progression of its severity as opposed to arising sui generis.From our database of >3000 patients with inflammatory bowel disease at Lenox Hill Hospital, we identified 45 patients with Crohn's ileitis and ileosigmoid fistula (ISF): 24 had segmental sigmoid polyps and 18 had segmental inflammatory sigmoid strictures. The fistula was first seen by imaging in 36 patients, but not until resection by the surgeon or dissection by the pathologist in 7 patients.The method of diagnosis for the initial recognition of the ISF and the sigmoid stricture is presented in Table 1. In 36 of the 45 cases, the ISF was recognized by radiologic imaging. In total, 31 of the 36 cases required surgical intervention, not because of the fistula, but because of small-bowel obstruction due to the ileitis. In 7 of the 31 (22%) cases, the fistula was recognized only by dissection of the inflammatory ileosigmoid mass by the surgeon or examination of the surgical specimen by the pathologist. The sequence of events from the originating ileitis to the ISF to the segmental sigmoid polyposis and stricture, with the resulting sigmoid obstruction, is shown in Figures 1A-E.We emphasize the natural history of the ISF so that its recognition will lead to earlier medical management of the originating ileitis. Furthermore, it adds evidence of the recognition that the causative agent of Crohn's disease is carried by the fecal stream.
- Excessive Daytime Sleepiness as an Indicator of Depression in Hispanic Americans. [JOURNAL ARTICLE]
- Hisp Health Care Int 2016 Jul 27.
Excessive daytime sleepiness (EDS) has been shown to be associated with depression; however, this relationship has not been confirmed among Hispanic Americans.This study examined the link between EDS and depression among Hispanic Americans (N = 411) and explored the potential moderating roles of age, gender, income, education, health status, and acculturation. The Epworth Sleepiness Scale and Patient Health Questionnaire-9 measured EDS and depression, respectively.Hierarchical linear regression demonstrated that EDS was significantly related to depression. Receiver operating characteristic curve analysis suggested that the Epworth Sleepiness Scale discriminated with adequate sensitivity and specificity between participants with moderately severe depression and those with less severe symptoms. No sociodemographic variables moderated the EDS-depression relationship.These findings suggest that depression should be considered when Hispanic Americans present with EDS.