Nutrient Intakes and Gastrointestinal Symptoms Among Esophagogastric Cancer Survivors up to 5 Years Post-Surgery.

A cross-sectional analysis explored nutritional intakes and gastrointestinal (GI) symptoms among esophagogastric cancer survivors up to 12, 13-36, and 37+ months post-surgery. Participants were identified from the Upper GI Cancer Registry at St James' Hospital, Ireland. The Short Nutritional Assessment Questionnaire, European Prospective Investigation of Cancer Food Frequency Questionnaire, World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Score, and Gastrointestinal Symptoms Rating Scale assessed malnutrition risk, nutritional intake, adherence to (secondary) cancer prevention recommendations, and GI symptoms, respectively. Most (82.5%, n33) participants (n40) were male. Mean age was 65.5 ± 9.3 years. Time post-surgery ranged from 6-62 months. Half (50.0%, n20) had a BMI in the healthy range. A quarter (27.5%, n11) were at risk of malnutrition. Intakes of meat and meat products exceeded recommendations and intakes of fruits, vegetables, and fiber were below recommendations, with no significant between-group differences. The mean WCRF/AICR score was 3.6 ± 1.1, indicating adherence to 3.6 of 7 cancer prevention recommendations. It was not significantly different between subgroups. Minor to mild GI discomfort was reported, with no significant between-group differences in symptoms. As rates of long-term survivorship continue to increase, survivors must be supported to sustain behaviors that enhance quality of life and reduce secondary cancer risk.

Measuring the impact of oesophagectomy on physical functioning and physical activity participation: a prospective study.

BACKGROUND: Oesophagectomy remains the only curative intervention for oesophageal cancer, with defined nutritional and health-related quality of life (HR-QOL) consequences. It follows therefore that there is a significant risk of decline in physical wellbeing with oesophagectomy however this has been inadequately quantified. This study prospectively examines change in physical functioning and habitual physical activity participation, from pre-surgery through 6-months post-oesophagectomy. METHODS: Patients scheduled for oesophagectomy with curative intent were recruited. Key domains of physical functioning including exercise tolerance (six-minute walk test (6MWT)) and muscle strength (hand-grip strength), and habitual physical activity participation, including sedentary behaviour (accelerometry) were measured pre-surgery (T0) and repeated at 1-month (T1) and 6-months (T2) post-surgery. HR-QOL was measured using the EORTC-QOL C30. RESULTS: Thirty-six participants were studied (mean age 62.4 (8.8) years, n = 26 male, n = 26 transthoracic oesophagectomy). Mean 6MWT distance decreased significantly from T0 to T1 (p = 0.006) and returned to T0 levels between T1 and T2 (p < 0.001). Percentage time spent sedentary increased throughout recovery (p < 0.001) and remained significantly higher at T2 in comparison to T0 (p = 0.003). In contrast, percentage time spent engaged in either light or moderate-to-vigorous intensity activity, all reduced significantly (p < 0.001 for both) and remained significantly lower at T2 in comparison to T0 (p = 0.009 and p = 0.01 respectively). Patients reported deficits in multiple domains of HR-QOL during recovery including global health status (p = 0.04), physical functioning (p < 0.001) and role functioning (p < 0.001). Role functioning remained a clinically important 33-points lower than pre-operative values at T2. CONCLUSION: Habitual physical activity participation remains significantly impaired at 6-months post-oesophagectomy. Physical activity is a measurable and modifiable target for physical rehabilitation, which is closely aligned with patient-reported deficits in role functioning. Rehabilitation aimed at optimising physical health in oesophageal cancer survivorship is warranted.

Outcomes of a Community-Based Paediatric Weight Management Programme in an Irish Midlands Setting.

Ongoing investigation is needed into feasible approaches which reduce excess weight in childhood. This study aimed to assess the effectiveness of an adapted version of the Scottish Childhood Overweight Treatment Trial (SCOTT) in an Irish primary care setting. Families were offered monthly dietitian-led sessions for six months. These sessions targeted dietary habits, family meals, screen time and exercise. Of the 95 children (mean age 7.6 years) referred, 90.5% (n86) were obese and 9.5% (n9) were overweight. Fifty-one (53.7%) families opted into the programme from referral, and 18 completed the programme (64.7% attrition). Statistically significant reductions in body mass index (BMI) were observed between sessions one and six (25.7±4.2kg/m2 and 25.3±4.8kg/m2, respectively, p<0.01). BMI z-score modestly decreased by 0.2 (p=0.01). Despite these reductions, issues with programme referral, attrition and long-term effectiveness were evident. Further investigation into strategies which reduce paediatric overweight is warranted.

Patient experiences of a physiotherapy-led multidisciplinary rehabilitative intervention after successful treatment for oesophago-gastric cancer.

PURPOSE: To qualitatively explore the perceived impact of a 12-week rehabilitative intervention for oesophago-gastric cancer survivors on their physical, mental and social wellbeing. METHODS: Of the 21 participants who completed the intervention, 19 took part in a semi-structured focus group interview. Four audio-taped focus groups were held, ranging in size from two to eight participants. Focus groups were transcribed and analysed using a descriptive qualitative approach. RESULTS: At recruitment, participants were 23.5 ± 15.2 months post-surgery and all had suboptimal fitness levels. Participants reported improvements in their physical capacity and ability to carry out activities of daily living during the intervention. These improvements led to increased confidence and social connectivity. Other participants were a valuable source of information and reassurance, while support from family members was variable. Future interventions should educate participants on how to maintain gains achieved during the intervention. CONCLUSIONS: Participating in an exercise-based multidisciplinary rehabilitative intervention reduces isolation and helps oesophago-gastric cancer survivors to safely negotiate their physical, emotional and social needs as they move further down the path of recovery.

Liming impacts on soils, crops and biodiversity in the UK: A review.

Fertile soil is fundamental to our ability to achieve food security, but problems with soil degradation (such as acidification) are exacerbated by poor management. Consequently, there is a need to better understand management approaches that deliver multiple ecosystem services from agricultural land. There is global interest in sustainable soil management including the re-evaluation of existing management practices. Liming is a long established practice to ameliorate acidic soils and many liming-induced changes are well understood. For instance, short-term liming impacts are detected on soil biota and in soil biological processes (such as in N cycling where liming can increase N availability for plant uptake). The impacts of liming on soil carbon storage are variable and strongly relate to soil type, land use, climate and multiple management factors. Liming influences all elements in soils and as such there are numerous simultaneous changes to soil processes which in turn affect the plant nutrient uptake; two examples of positive impact for crops are increased P availability and decreased uptake of toxic heavy metals. Soil physical conditions are at least maintained or improved by liming, but the time taken to detect change varies significantly. Arable crops differ in their sensitivity to soil pH and for most crops there is a positive yield response. Liming also introduces implications for the development of different crop diseases and liming management is adjusted according to crop type within a given rotation. Repeated lime applications tend to improve grassland biomass production, although grassland response is variable and indirect as it relates to changes in nutrient availability. Other indicators of liming response in grassland are detected in mineral content and herbage quality which have implications for livestock-based production systems. Ecological studies have shown positive impacts of liming on biodiversity; such as increased earthworm abundance that provides habitat for wading birds in upland grasslands. Finally, understanding of liming impacts on soil and crop processes are explored together with functional aspects (in terms of ecosystems services) in a new qualitative framework that includes consideration of how liming impacts change with time. This holistic approach provides insights into the far-reaching impacts that liming has on ecosystems and the potential for liming to enhance the multiple benefits from agriculturally managed land. Recommendations are given for future research on the impact of liming and the implications for ecosystem services.

Sarcopenia during neoadjuvant therapy for oesophageal cancer: characterising the impact on muscle strength and physical performance.

PURPOSE: Preoperative chemo(radio)therapy for oesophageal cancer (OC) may have an attritional impact on body composition and functional status, impacting postoperative outcome. Physical decline with skeletal muscle loss has not been previously characterised in OC and may be amenable to physical rehabilitation. This study characterises skeletal muscle mass and physical performance from diagnosis to post-neoadjuvant therapy in patients undergoing preoperative chemo(radio)therapy for OC. METHODS: Measures of body composition (axial computerised tomography), muscle strength (handgrip), functional capacity (walking distance), anthropometry (weight, height and waist circumference), physical activity, quality-of-life and nutritional status were captured prospectively. Sarcopenia status was defined as pre-sarcopenic (low muscle mass only), sarcopenic (low muscle mass and low muscle strength or function) or severely sarcopenic (low muscle mass and low muscle strength and low muscle function). RESULTS: Twenty-eight participants were studied at both time points (mean age 62.86 ± 8.18 years, n = 23 male). Lean body mass reduced by 4.9 (95% confidence interval 3.2 to 6.7) kg and mean grip strength reduced by 4.3 (2.5 to 6.1) kg from pre- to post-neoadjuvant therapy. Quality-of-life scores capturing gastrointestinal symptoms improved. Measures of anthropometry, walking distance, physical activity and nutritional status did not change. There was an increase in sarcopenic status from diagnosis (pre-sarcopenic n = 2) to post-treatment (pre-sarcopenic n = 5, severely sarcopenic n = 1). CONCLUSIONS: Despite maintenance of body weight, functional capacity and activity habits, participants experience declines in muscle mass and strength. Interventions involving exercise and/or nutritional support to build muscle mass and strength during preoperative therapy, even in patients who are functioning normally, are warranted.

Influence of microporosity in SBA-15 on the release properties of anticancer drug dasatinib.

The release of the hydrophobic cancer drug dasatinib from two mesoporous silica materials as drug delivery vehicles has been studied. One material is a reference 2D-hexagonal SBA-15 with the typical bimodal pore system with ordered primary mesopores and disordered intrawall pores. The other material is a modified version of the same material where the intrawall porosity in the micropore regime has been selectively removed. Material characterization shows that, with the exception of the difference in intrawall porosity, the materials have identical properties. The drug dasatinib, a tyrosine kinase inhibitor, has been loaded, to the same extent, into the pores of both materials. The two materials give rise to very different release profiles of the drug. The presence of micropores leads to desired release properties: a high initial release of the drug, which is maintained over time. The lack of micropores also leads to a high initial release but followed by a rapid drop in the concentration of released drug, a consequence of its low solubility and hence crystallisation. We suggest that the presence of micropores in the carrier material, and the resultant kinetic release profile, leads to a stabilization of dasatinib in solution and to a sustained supersaturated level of the released drug. Our findings suggest that by controlling the mesoporous host with small variation in the textural properties, the kinetic release and crystallization behaviour of a drug can be altered. It is thus potentially possible to influence the drug post-release and thereby its bioavailability.

Weaning onto solid foods: some of the challenges.

Weaning--the transition from milk to solid food--influences life-long health. Dietary challenges during weaning include providing sufficient critical nutrients such as iron with minimal added sugar and fat and no added salt. This study assessed the inclusion of iron-containing red meat in infant diets before age one year, and the Irish commercial baby food environment. Of mothers with an infant under 30 months of age who were surveyed in shopping centres in Ireland (n195), 82% (n159) reported wanting more weaning information. A quarter (n24) of infants over age 12 months (n97) received no iron-containing red meat before age one year. A scan of commercial baby foods in Ireland identified 448 products. While all complied with baby food legislation, 15% (n69) were intrinsically high in sugar and fat, or contained added salt. This study indicates the need for specific guidance on best infant feeding practice in Ireland.

Granulomas in Crohn's disease: does progression through the bowel layers affect presentation or predict recurrence?

AIM: The aim of the study was to correlate the presence and pattern of distribution of granulomas in resected specimens to clinical characteristics and outcome in patients undergoing surgery for Crohn's disease. METHOD: Patients with Crohn's disease who underwent surgical resection between 2001 and 2007 were identified. Pathology slides were reviewed for the presence, number and location of granulomas in four representative slides from each specimen. RESULTS: Two-hundred and seven patients were identified. At a mean follow up of 14 months, 39 patients had a recurrence, 22 (57%) of whom underwent reoperation. Ninety-four (45%) patients had granulomas present in the surgical specimen. Patients with granulomas were younger (P<0.001), had a lower preoperative body mass index (P=0.037), were more likely to be female (P=0.017) and were more likely to have extra-intestinal manifestations (P=0.026) or perianal disease (P=0.012). Sites of disease and procedures performed were similar in both groups. Disease recurrence and reoperative rates were similar in both groups, as were length of stay and morbidity rates. The average number of granulomas present in each sampled pathology slide was 7.2, and there was no correlation between number of granulomas and disease severity. No link was found between the depth of involvement of the granulomas and fistulizing or stricturing disease. CONCLUSION: Granulomas were associated with increased extra-intestinal manifestations and perianal disease, a lower body mass index and younger or female patients. There was no correlation between the presence of granulomas and disease progression or recurrence rates during the short follow-up period of this study.

Collagenous pouchitis.

Collagenous colitis is characterised by watery diarrhoea, normal colonic mucosa on endoscopy, diffuse colitis with surface epithelial injury, and a distinctive thickening of the subepithelial collagen table on histology. Some patients can develop medically refractory collagenous colitis, in which case they may require surgical intervention. This is the first report of collagenous pouchitis in a collagenous colitis patient with proctocolectomy and ileal pouch-anal anastomosis. A patient with medically refractory collagenous colitis who underwent a total proctocolectomy and ileal pouch-anal anastomosis was sequentially evaluated with an endoscopy and histology of the colon, distal small intestine, and ileal pouch. A 58-year-old female had a 10-year history of collagenous colitis before having a total proctocolectomy and ileal pouch-anal anastomosis for medically refractory disease. The histologic features of collagenous colitis were present in all colon and rectum biopsy or resection specimens, but were absent in the distal ileum specimen. The post-operative course was complicated by persistent increase of stool frequency, abdominal cramps, and incontinence. A pouch endoscopy was performed 3 years after ileal pouch-anal anastomosis which showed the histologic features of collagenous colitis in the ileal pouch, collagenous pouchitis, while the pre-pouch neo-terminal ileum had no pathologic changes. After antibiotic therapy, the histologic changes of collagenous pouchitis resolved. This is the first reported case of collagenous pouchitis. Since the abnormal collagen table and its associated features were only present in the pouch and absent in the neo-terminal ileum, and the patient had histologic improvement after antibiotic therapy, it would suggest that faecal stasis and bacterial load may play a role in the pathogenesis.

Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: experience in clinical practice.

BACKGROUND: Management of antibiotic-dependent pouchitis is often challenging. Oral bacteriotherapy with probiotics (such as VSL #3) as maintenance treatment has been shown to be effective in relapsing pouchitis in European trials. However, this agent has not been studied in the US, and its applicability in routine clinical practice has not been evaluated. AIM: To determine compliance and efficacy of probiotic treatment in patients with antibiotic-dependent pouchitis. METHODS: Thirty-one patients with antibiotic-dependent pouchitis were studied. VSL #3 is a patented probiotic preparation of live freeze-dried bacteria. All patients received 2 weeks of ciprofloxacin 500 mg b.d. followed by VSL #3 6 g/day for 8 months. Baseline Pouchitis Disease Activity Index scores were calculated. Patients' symptoms were reassessed at week 3 when VSL #3 therapy was initiated and at the end of the 8-month trial. Some patients underwent repeat pouch endoscopy at the end of the trial. RESULTS: All 31 patients responded to the 2-week ciprofloxacin trial with resolution of symptoms and they were subsequently treated with VSL #3. The mean duration of follow-up was 14.5+/-5.3 months (range: 8-26 months). At the 8-month follow-up, six patients were still on VSL #3 therapy, and the remaining 25 patients had discontinued the therapy due to either recurrence of symptoms while on treatment or development of adverse effects. All six patients who completed the 8-month course with a mean treatment period of 14.3+/-7.2 months (range: 8-26 months) had repeat clinical and endoscopic evaluation as out-patients. At the end of 8 months, these six patients had a mean Pouchitis Disease Activity Index symptom score of 0.33+/-0.52 and a mean Pouchitis Disease Activity Index endoscopy score of 1.83+/-1.72, which was not statistically different from the baseline Pouchitis Disease Activity Index endoscopy score of 2.83+/-1.17 (P=0.27). CONCLUSION: This study was conducted to evaluate bacteriotherapy in routine care. The use of probiotics has been adopted as part of our routine clinical practice with only anecdotal evidence of efficacy. Our review of patient outcome from the treatment placebo showed that only a minority of patients with antibiotic-dependent pouchitis remained on the probiotic therapy and in symptomatic remission after 8 months.

Discordant results of CK-MB and troponin I measurements: a review of 14 cases.

In the course of a clinical comparison involving 204 parallel total creatine kinase (CK), creatine kinase-MB isoenzyme (CK-MB), and cardiac troponin I (cTnI) measurements, 12 patients were identified in whom cTnI was elevated while total CK was normal, as well as 2 patients in whom CK-MB was elevated while cTnI was normal. CK-MB relative index was elevated in 6 of the twelve cTnI-positive patients with normal total CK; only 2 of these patients had a discharge diagnosis of acute myocardial infarction (AMI). All of the 12 patients in this group had medical conditions that are associated with greater risk for acute cardiac events. Both patients with normal cTnI but elevated total CK and CK-MB index had chronic renal insufficiency; one of these patients had a positive stress test and a diagnosis of AMI. The other cTnI-negative patient died 2 days after admission, and autopsy revealed evidence of ischemic changes, but not acute infarction. Significant differences were apparent between traditional CK-MB results and cTnI measurements. Using total CK elevation as a prerequisite for subsequent CK-MB measurement may limit the clinical sensitivity of this enzyme marker for detecting subacute ischemic damage to the myocardium. Elevated total CK and CK-MB isoenzyme without corresponding elevations in cTnI, on the other hand, may reflect changes in enzyme elimination kinetics due to renal failure, or cross-reactivity of the cTnI assay with non-cardiac antigens.

Structural investigation of the active site in bacteriorhodopsin: geometric constraints on the roles of Asp-85 and Asp-212 in the proton-pumping mechanism from solid state NMR.

Constraints on the proximity of the carboxyl carbons of the Asp-85 and Asp-212 side chains to the 14-carbon of the retinal chromophore have been established for the bR(555), bR(568), and M(412) states of bacteriorhodopsin (bR) using solid-state NMR spectroscopy. These distances were examined via (13)C-(13)C magnetization exchange, which was observed in two-dimensional RF-driven recoupling (RFDR) and spin diffusion experiments. A comparison of relative RFDR cross-peak intensities with simulations of the NMR experiments yields distance measurements of 4.4 +/- 0.6 and 4.8 +/- 1.0 A for the [4-(13)C]Asp-212 to [14-(13)C]retinal distances in bR(568) and M(412), respectively. The spin diffusion data are consistent with these results and indicate that the Asp-212 to 14-C-retinal distance increases by 16 +/- 10% upon conversion to the M-state. The absence of cross-peaks from [14-(13)C]retinal to [4-(13)C]Asp-85 in all states and between any [4-(13)C]Asp residue and [14-(13)C]retinal in bR(555) indicates that these distances exceed 6.0 A. For bR(568), the NMR distance constraints are in agreement with the results from recent diffraction studies on intact membranes, while for the M state the NMR results agree with theoretical simulations employing two bound waters in the region of the Asp-85 and Asp-212 residues. The structural information provided by NMR should prove useful for refining the current understanding of the role of aspartic acid residues in the proton-pumping mechanism of bR.

Solid-state NMR evidence for an antibody-dependent conformation of the V3 loop of HIV-1 gp120.

Solid-state NMR measurements have been carried out on frozen solutions of the complex of a 24-residue peptide derived from the third variable (V3) loop of the HIV-1 envelope glycoprotein gp120 bound to the Fab fragment of an anti-gp120 antibody. The measurements place strong constraints on the conformation of the conserved central GPGR motif of the V3 loop in the antibody-bound state. In combination with earlier crystal structures of V3 peptide-antibody complexes and existing data on the cross-reactivity of the antibodies, the solid-state NMR measurements suggest that the Gly-Pro-Gly-Arg (GPGR) motif adopts an antibody-dependent conformation in the bound state and may be conformationally heterogeneous in unbound, full-length gp120. These measurements are the first application of solid-state NMR methods in a structural study of a peptide-protein complex.

Focal necrotizing endometritis: a clinicopathologic study of 15 cases.

From routine sign-out of endometrial biopsy specimens, a group of 15 endometria were identified that have a characteristic histologic pattern of inflammation that is not included in present classifications of endometritis. All but one of the women were premenopausal, and all presented with abnormal vaginal bleeding. The lesion is characterized by a patchy, focal inflammation, usually composed of lymphocytes with a variable number of neutrophils and rare macrophages centered around endometrial glands and extending into the glandular lumen with disruption and partial or subtotal necrosis of the endometrial glandular epithelium. These foci were widely dispersed, never confluent, and could be overlooked easily. Plasma cells were not found in any of the endometrial specimens despite methyl green pyronine staining of the samples. Based on the histologic characteristics of this process we have designated it focal necrotizing endometritis. The clinical significance, if any, of focal necrotizing endometritis is currently unknown.

Insulin-like growth factors I and II in children with systemic onset juvenile arthritis.

Systemic onset juvenile arthritis (JA) has been associated with growth failure in children whether or not treated with adrenocorticosteroids. Growth hormone secretion has been reported to be normal, but production of insulin-like growth factors has not been studied. We measured serum concentrations of insulin-like growth factor I and II in a group of children with systemic JA at different times, and during treatment with only nonsteroidal antiinflammatory therapy or while receiving prednisone. Mean concentrations of insulin-like growth factor I and II were below normal for age whether or not prednisone was being given. Growth failure during periods of active disease was observed in both groups. Only 4 of 11 prepubertal children in whom growth rates were measured grew 4.5 cm or more/year. However, longitudinal studies of individual children showed that lowest growth rates occurred while taking prednisone and that growth rates were not correlated to insulin-like growth factor levels.

Purification and comparison of the receptors for insulin and insulin like growth factor I.

The insulin-like growth factors are structurally and biologically similar to insulin. The receptor sites for insulin-like growth factor-I have recently been shown to have a sub-unit structure very similar if not identical to insulin. We have compared the behavior of insulin and insulin-like growth factor-I receptors during purification using gel filtration, lectin affinity chromatography, insulin affinity chromatography, and gel electrophoresis. We demonstrate the remarkably similar physicochemical characteristics of these two receptors, but have achieved complete separation by the use of insulin affinity chromatography.

Insulin-like growth factors I and II: aging and bone density in women.

Serum concentrations of insulin-like growth factors (IGF) were measured by RIA in 57 normal women, ages 30 - 90 yr, and in 29 untreated women with postmenopausal osteoporosis and vertebral compression fractures, ages 55 - 75 yr. These values were correlated with bone mineral density (BMD) of the distal and midradius assessed by single photon absorptiometry and of the lumbar spine assessed by dual photon absorptiometry as well as serum and urinary calcium, phosphorus, creatinine, alkaline phosphatase, immunoreactive PTH, urinary hydroxyproline, and creatinine clearance. Serum IGF-I levels declined markedly with age (r = -0.47, P less than 0.001). Serum IGF-II levels decreased only slightly with age, and this decrease was not statistically significant. Although BMD at all three scanning sites also declined significantly with age, neither serum IGF-I nor II concentrations correlated with BMD when age was held constant. In women with postmenopausal osteoporosis, serum IGF-I and II did not differ from the concentrations in normal women of similar age and did not correlate with BMD. In neither group was a correlation between serum IGF-I or II and serum or urinary proteins or cations found. Thus, there was no evidence that impaired synthesis of IGF-I and II contributes to pathogenesis of the syndrome of Type I (postmenopausal) osteoporosis, which is characterized by accelerated loss of trabecular bone and vertebral compression fractures. The possibility remains, however, that decreasing concentrations of serum IGF-I play a role in the more gradual loss of bone with aging (Type II osteoporosis) in which impared bone formation at the cellular level has been demonstrated.