A window beneath the skin: how computed tomography assessment of body composition can assist in the identification of hidden wasting conditions in oncology that profoundly impact outcomes.

Advancements in image-based technologies and body composition research over the past decade has led to increased understanding of the importance of muscle abnormalities, such as low muscle mass (sarcopenia), and more recently low muscle attenuation (MA), as important prognostic indicators of unfavourable outcomes in patients with cancer. Muscle abnormalities can be highly prevalent in patients with cancer (ranging between 10 and 90 %), depending on the cohort under investigation and diagnostic criteria used. Importantly, both low muscle mass and low MA have been associated with poorer tolerance to chemotherapy, increased risk of post-operative infectious and non-infectious complications, increased length of hospital stay and poorer survival in patients with cancer. Studies have shown that systemic antineoplastic treatment can exacerbate losses in muscle mass and MA, with reported loss of skeletal muscle between 3 and 5 % per 100 d, which are increased exponentially with progressive disease and proximity to death. At present, no effective medical intervention to improve muscle mass and MA exists. Most research to date has focused on treating muscle depletion as part of the cachexia syndrome using nutritional, exercise and pharmacological interventions; however, these single-agent therapies have not provided promising results. Rehabilitation care to modify body composition, either increasing muscle mass and/or MA should be conducted, and its respective impact on oncology outcomes explored. Although the optimal timing and treatment strategy for preventing or delaying the development of muscle abnormalities are yet to be determined, multimodal interventions initiated early in the disease trajectory appear to hold the most promise.

Long-term follow-up of the incidence of Helicobacter pylori.

OBJECTIVES: Helicobacter pylori causes peptic ulcer disease and gastric cancer. Understanding the incidence of H. pylori could help guide research on potential infection prevention strategies. Previous studies indicate infection occurs in young children, but the risk of infection in older children and adolescents is unclear. Our hypothesis was that H. pylori infection is rare in adolescence or adulthood. Our aim was to determine the incidence of H. pylori over a prolonged follow-up in a cohort of 626 noninfected individuals. METHODS: Participants, including index children, mothers, fathers and siblings, from a previous study (1997-2002) were traced, and 883 of 946 participated in this extended follow-up. We used the 13C urea breath test (13C-UBT) to determine the incidence of H. pylori among 626 family members not infected in 2002, including 75 younger siblings who were not born or too young for testing in 2002. RESULTS: Eight (3.8%) of 210 index participants (mean ± standard deviation age 17.92 ± 0.77 years) became infected during 11.07 ± 0.56 years of follow-up (incidence, 3.42 per 1000 person-years; 95% confidence interval (CI), 1.48-6.74). Only one (0.6%) of 165 older siblings became infected (incidence, 0.57 per 1000 person-years; 95% CI, 0.007-3.16) and one of 176 parents became infected (incidence, 0.63 per 1000 person-years; 95% CI, 0.01-3.5). Of 75 younger siblings (age 10.9 ± 2.85 years) who were too young for testing or not yet born in 2002, nine (12%) became infected (incidence, 11.32 per 1000 person-years; 95% CI, 5.27-21.49). The highest incidence of H. pylori infection was in those born after 2005. CONCLUSIONS: The incidence of H. pylori was extremely low in older children and adults in developed countries. Spontaneous clearance of infection was uncommon in our study population.

Is diffusion-weighted MRI sufficient for follow-up of neuroendocrine tumour liver metastases?

AIM: To assess if diffusion-weighted imaging (DWI) alone could be used for follow-up of neuroendocrine hepatic metastases. MATERIAL AND METHODS: This was a retrospective study, approved by the institutional review board. Twenty-two patients with neuroendocrine liver metastases who had undergone more than one liver magnetic resonance imaging (MRI) examination, (including DWI and using hepatocyte-specific contrast medium) were evaluated. Up to five metastases were measured at baseline and at each subsequent examination. The reference standard measurement was performed on the hepatocyte phase by one reader. Three independent readers separately measured the same lesions on DWI sequences alone, blinded to other sequences, and recorded the presence of any new lesions. RESULTS: The longest diameters of 317 liver metastases (91 on 22 baseline examinations and a further 226 measurements on follow-up) were measured on the reference standard by one reader and on three b-values by three other readers. The mean difference between DWI measurements and the reference standard measurement was between 0.01-0.08 cm over the nine reader/b-value combinations. Based on the width of the Bland and Altman interval containing approximately 95% of the differences between the reader observation and the mean of reference standard and DWI measurement, the narrowest interval over the nine reader/b-value combinations was -0.6 to +0.7 cm and the widest was -0.9 to 1 cm. In the evaluation of overall response using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria, the weighted kappa statistic was between 0.49 and 0.86, indicating moderate-to-good agreement between the reference standard and DWI. CONCLUSION: The visualisation and measurement of hepatic metastases using DWI alone are within acceptable limits for clinical use, allowing the use of this rapid technique to restage hepatic disease in patients with neuroendocrine metastases.

Novel placental ultrasound assessment: potential role in pre-gestational diabetic pregnancy.

OBJECTIVES: Management of women with pre-gestational diabetes continues to be challenging for clinicians. This study aims to determine if 3D power Doppler (3DPD) analysis of placental volume and flow, and calculation of placental calcification using a novel software method, differ between pregnancies with type 1 or type 2 diabetes and normal controls, and if there is a relationship between these ultrasound placental parameters and clinical measures in diabetics. METHODS: This was a prospective cohort study of 50 women with diabetes and 250 controls (12-40 weeks gestation). 3DPD ultrasound was used to evaluate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Placental calcification was calculated by computer analysis. Results in diabetics were compared with control values, and correlated with early pregnancy HbA1c, Doppler results and placental histology. RESULTS: Placental calcification and volume increased with advancing gestation in pre-gestational diabetic placentae. Volume was also found to be significantly higher than in normal placentae. VI and VFI were significantly lower in diabetic pregnancies between 35 and 40 weeks gestation. A strong relationship was seen between a larger placental volume and both increasing umbilical artery pulsatility index and decreasing middle cerebral artery pulsatility index. FI was significantly lower in cases which had a booking HbA1c level ≥6.5%. Ultrasound assessed placental calcification was reduced with a histology finding of delayed villous maturation. No other correlation with placental histology was found. CONCLUSIONS: This study shows a potential role for 3D placental evaluation, and computer analysis of calcification, in monitoring pre-gestational diabetic pregnancies.

Smoking in vehicles is lower than mobile telephone use while driving, but is socially patterned.

Legislation is being considered which bans smoking in cars carrying children under the age of 16. This was an observational survey of smoking by drivers and passengers and mobile phone use by drivers in 2,230 cars over three time periods in two Dublin locations. The observed prevalence of mobile telephone use (2.56%) was higher than smoking (1.39%) (p < 0.01), but was low in both. There was no significant variation according to time of day. There was an inverse pattern according to car value for smoking drivers (p = 0.029). Eight adult passengers and just one child were observed as being exposed to a smoking adult driver. In conclusion, the public health importance of regulating passive smoke exposure is clear but the resources required to police such a ban in vehicles may be labour intensive for the yield in detection or prevention.

Does the developmental plasticity hypothesis have application to Irish Travellers? Findings from the all Ireland Traveller Health Study birth cohort 2008-2011.

There is little record of birth weight of Irish Travellers, a minority group in Ireland. Travellers are known to have higher rate of adult chronic disease and to be exposed to life-long disadvantage. The aim of this study was to establish whether the birth weight and infant mortality rate patterns in Ireland's Travellers were consistent with the developmental plasticity hypothesis. A 1-year follow-up birth cohort study was conducted with linkage data from maternity hospital records of Traveller infants born on the island of Ireland over a 12-month period to self-identifying Traveller and general Irish population mothers from the Lifeways Cross-Generation Cohort Study. The main outcome measure was the rate of birth weight <3000 g in a cohort of Traveller children. There were 987 confirmed Traveller births, 500 of whose mothers consented to linkage to their records. A social gradient was observed in the distribution of birth weight in the general population and Traveller infants constituted the highest proportion of all social classes in the birth weight range of 3 kg or less (16.3%). There was a high rate of persistent smoking among Traveller mothers (53%). After adjustment for smoking and alcohol consumption in pregnancy, the birth weight differential persisted (OR 3.5, 95% CI 1.4-8.1). Infant mortality rate at 12.0/1000 births (95% CI 5.5-19.7) was almost four times that of the general population. This analysis confirms Travellers had a greater than expected incidence of low birth weight and high infant mortality with high rates of premature adult chronic diseases from all causes already demonstrated previously.

Socio-demographic, environmental, lifestyle and psychosocial factors predict self rated health in Irish Travellers, a minority nomadic population.

Irish Travellers are an indigenous nomadic minority group with poor life expectancy. As part of a census survey of Travellers (80% participation rate), a health status interview was conducted (n=2065, 43.5% male). In the final regression model, positive predictors of self-rated health (SRH) were having a flush toilet (OR 2.2, p=0.021), considering where one lives to be healthy (OR 1.9, p=0.017), travelling twice yearly (OR 2.3 p=0.026), taking a brisk walk weekly (OR 2.4, p=0.000) and non-smoking (OR 1.7, p=0.03). Conversely, SRH was negatively associated with age (p=0.000), activity-limiting ill health (OR 0.4, p=0.001), or chronic health condition (OR 0.4, p=0.002).

Delayed cystic fibrosis presentation in children in the absence of newborn screening.

Newborn cystic fibrosis (CF) screening facilitates early diagnosis and nutritional intervention, which prevents malnourishment and improves growth in childhood. To provide baseline information on the natural history of CF in the Republic of Ireland, where newborn screening has not yet been introduced and CF incidence is high (1:1353 live births), we examined the effect of presentation mode, symptom type and gender on age at diagnosis. Median age at diagnosis was calculated by gender and for presentation mode/symptom type for 601 CF registry children diagnosed 1986-2007. Modes of presentation were each significantly associated with delayed presentation. An adjusted odds ratio of 4.5 (95% CI: 1.8, 11.1) was determined for presentation with family history, 43.1 for gastrointestinal symptoms presentation (95% CI: 18.3, 101.4), 96.9 for both respiratory and gastrointestinal symptoms (95% CI: 38.6, 243,4), and 115.4 for respiratory symptoms (95% CI: 45.2, 294.7). Children with respiratory symptoms had the greatest likelihood of delayed diagnosis (median age: 20.4 months), followed by those with respiratory and gastrointestinal symptoms (9.2 months). Gender was not significantly associated with a delayed presentation when presentation mode was taken into account.

Genetic variants of microsomal epoxide hydrolase and glutamate-cysteine ligase in COPD.

The genetic factors that contribute to the development of chronic obstructive pulmonary disease (COPD) are poorly understood. Many candidate genes have been proposed, including enzymes that protect the lung against oxidative stress, such as microsomal epoxide hydrolase (EPHX1) and glutamate-cysteine ligase (GCL). To date, most reported findings have been for EPHX1, particularly in relation to functional variants associated with fast and slow metabolism of epoxide intermediates. The present study aimed to identify any association of variation in these genes with COPD susceptibility or severity. In total, 1,017 white COPD patients and 912 nondiseased age and sex matched smoking controls were genotyped for six single nucleotide polymorphisms (SNPs) in EPHX1 (including the fast and slow variants and associated haplotypes), and eight SNPs in the two genes encoding GCL. GCL is a rate-limiting enzyme in the synthesis of glutathione, a major contributor to anti-oxidant protection in the lung. No association of variation was found in EPHX1 or GCL with susceptibility to COPD or disease severity. This is the largest reported study to date and is well powered to detect associations that have been previously suggested. The current data indicate that these genetic variants are unlikely to be related to susceptibility or disease severity in white chronic obstructive pulmonary disease patients.

Trends in medical student use of tobacco, alcohol and drugs in an Irish university, 1973-2002.

Questionnaire surveys of medical students in an Irish university were carried out in 1973 (n=765), 1990 (n=522) and 2002 (n=537), with differentiation of western students (e.g., from the Republic of Ireland, the UK, or Australia) and non-western students (e.g., Malaysia). We report on changes in tobacco smoking, drinking and drug-taking over three decades, and we note that, among western students, estimated prevalence of being a current smoker has declined overall from 28.8% in 1973 to 15.3% in 1990 to 9.2% in 2002 (p<0.001), falling in both males (p<0.001) and females (p<0.01). Ex-smokers rose from 5.9% to 15.1% between 1990 and 2002, corresponding with the decline in current smokers. The prevalence of current drinkers has risen over the period, to 82.5% among western students in 2002 (p<0.05); female drinking has increased steadily since 1973 (p<0.001), and the overall proportion of CAGE-positive drinkers has risen since 1990 (p<0.001). The mean weekly alcohol consumption has risen in both sexes since 1990 (males 14.3 units to 19.4, p<0.01; females 6.0 to 9.5, p<0.001). There was an increase in the proportion of students ever offered drugs between 1973 and 2002 (p<0.001). Although smoking rates have fallen, our findings show a marked increase in alcohol and drug consumption between 1973 and 2002. Personal misuse of addictive substances by doctors may mean that doctors will fail to take misuse by patients seriously. A need for preventative and ameliorative action during the medical school years is clear.

The "Americanisation" of migrants: evidence for the contribution of ethnicity, social deprivation, lifestyle and life-course processes to the mid-20th century Coronary Heart Disease epidemic in the US.

We investigated the contribution of the large-scale immigration of White Europeans into the US between 1850 and 1930 to the timing and extent of the epidemic pattern of heart disease between 1900 and 1980. The analyses are based on data collected through the United States Federal Census from 1850 to the present. The hardcopy historical record confirms that census reports themselves and related monographs were concerned from 1850 with excessive mortality from heart disease of immigrants, particularly of Northern European origin and initially at least, their first-generation native-born children. Our analysis of the electronic database indicates a strong relationship between the percentage of US population foreign born and native born of foreign parentage and age adjusted mortality from heart disease. We identified a lag of 50 years giving the maximum linear correlation coefficient for men (r(2) = 0.92), and for women a shorter lag of 38 years and an earlier decline in Coronary Heart Disease (CHD) rates (r(2) = 0.96). Both the rise and fall of the CHD epidemic over an 80-year period correspond closely to the rise and fall of the foreign population in previous years. For the foreign born only, age adjusted negative binomial general estimated equation (GEE) models calculate the relative risk of dying of heart disease per 10% increase in proportion foreign born. There is an independent influence for men until 1930 and for women throughout the period from 1910 onwards. We conclude there is an impact of immigration on the pattern of the epidemic, mediated through a combination of factors, such as accumulated life-course susceptibility, deprived socio-economic conditions upon arrival, and the enthusiastic uptake of behaviours related to the classic risk factors of smoking, high saturated fat and salt diet. Our analysis provides a more contextualised understanding of the scale and timing of the epidemic of CHD in the US.

Estimation of the gas exchange threshold in humans: a time series approach.

An autoregressive moving average model is presented for detecting the gas exchange threshold (GET) from gas exchange response data taken during an incremental exercise test. The approach has the advantage of modelling the serial correlation in the noise between observations from the same subject. The model is fitted by maximum likelihood and a breakpoint or threshold in the mean function is the estimated GET. It is shown how an estimate of standard error can be obtained by bootstrapping the residuals from the fitted model. To evaluate the approach, gas exchange data on 14 healthy subjects during a ramp exercise test (20 W x min(-1)) to the limits of tolerance, were analysed. The results are compared to the v-slope method and to the method of maximum likelihood assuming independent noise.

Cancer pain assessment.

Regardless of their area of clinical practice, nurses are faced on a daily basis with the challenge of effectively managing their patient's pain. Despite significant technological advances, inadequate treatment of pain is still widely reported in the literature.

HLS7, a hemopoietic lineage switch gene homologous to the leukemia-inducing gene MLF1.

Hemopoietic lineage switching occurs when leukemic cells, apparently committed to one lineage, change and display the phenotype of another pathway. cDNA representational difference analysis was used to identify myeloid-specific genes that may be associated with an erythroid to myeloid lineage switch involving the murine J2E erythroleukemic cell line. One of the genes isolated (HLS7) is homologous to the novel human oncogene myeloid leukemia factor 1 (MLF1) involved in the t(3;5)(q25.1;q34) translocation associated with acute myeloid leukemia. Enforced expression of HLS7 in J2E cells induced a monoblastoid phenotype, thereby recapitulating the spontaneous erythroid to myeloid lineage switch. HLS7 also inhibited erythropoietin- or chemically-induced differentiation of erythroleukemic cell lines and suppressed development of erythropoietin-responsive colonies in semi-solid culture. However, intracellular signaling activated by erythropoietin was not impeded by ectopic expression of HLS7. In contrast, HLS7 promoted maturation of M1 monoblastoid cells and increased myeloid colony formation in vitro. These data show that HLS7 can influence erythroid/myeloid lineage switching and the development of normal hemopoietic cells.

Coexpression of the HER-2 gene product, p185HER-2, and epidermal growth factor receptor, p170EGF-R, on epithelial ovarian cancers and normal tissues.

Monoclonal antibodies (MAbs) and immunoconjugates reactive with different antigens expressed by neoplastic cells can inhibit tumor growth. Use of these agents in combination with one another or with chemotherapy can exert additive or synergistic cytotoxicity against tumor cells. An augmented therapeutic activity with favorable therapeutic index might be attained when coexpression is observed on tumor cells, but not in normal tissues. In this study frozen sections of 19 ovarian cancers (2 stage I, 10 stage III, 2 stage IV, and 5 recurrent), as well as 29 normal tissues, were evaluated by immunohistochemistry using 11 distinct MAbs against HER-2/p185 and 2 antibodies against EGF-R/p170 to assess coexpression of these receptors. HER-2/p185 expression was detected in 5 to 100% of ovarian cancers and 0 to 50% of normal ovarian epithelia, depending on the antibody used. EGF-R/p170 expression was detected in approximately 70% of cancers and 40% of normal ovaries by both antibodies. Coexpression of p185 and p170 was observed in 47-68% of ovarian cancers and 9-18% of normal ovarian epithelial specimens depending upon the combination of antibodies used. Staining of 273 specimens from 29 normal tissues indicated that coexpression of HER-2 and EGF-R is rare. Normal tissues that coexpressed both receptors in > or =50% of the cases included cervix, endometrium, esophagus, skin, and prostate. These data confirm that HER-2 and EGF-R are more frequently expressed in advanced ovarian cancers than in normal ovarian epithelium and a significant fraction of these tumors coexpress both HER-2 and EGF-R.

Pregnancy outcome after laparoscopic electromyolysis.

Laparoscopic myolysis, a procedure designed to shrink uterine myomas by coagulating their blood supply, is an alternative to myomectomy or hysterectomy in women who do not contemplate childbearing. Three patients conceived within 3 months after myolysis against the surgeon's advice. In two of these women the uterus ruptured at 32 and 39 weeks' gestation, respectively, associated with death of the 32-week fetus. The third patient had an uneventful elective cesarean section at 39 weeks' gestation. Until the risk of uterine rupture after myolysis has been accurately compared with that after myomectomy, women should not undergo myolysis if they wish to conceive. Should pregnancy occur after myolysis, caution and intensive surveillance of mother and fetus must be applied, and cesarean section should be performed at earliest signs and symptoms of uterine rupture and at term before onset of labor.