Six-month outcomes of teduglutide treatment in adult patients with short bowel syndrome with chronic intestinal failure: A real-world French observational cohort study.

BACKGROUND & AIMS: Teduglutide, a GLP-2-analog, has proven effective in two placebo-controlled studies in reducing parenteral support (PS) in patients with short bowel syndrome-associated intestinal failure (SBS-IF) after 24 weeks. The aim of this study was to describe in a real-life situation the effects of teduglutide treatment and their predictive factors. METHODS: We included 54 consecutive SBS-IF patients treated with teduglutide in France for at least 6 months from 10 expert centers. Small bowel length was 62 ± 6 cm and 65% had colon in continuity. PS was 4.4 ±0 .2 infusions per week, started 9.8 ± 1.2 years before. Response (PS reduction ≥ 20%) and PS discontinuation rates were assessed at week 24. Adjusted p values of factors associated with response and weaning were calculated using a multivariate logistic regression model. RESULTS: At week 24, 85% of patients were responders and 24% had been weaned off PS, with a 51% reduction of PS needs and 1.5 ± 0.2 days off PS per week. Response to teduglutide was influenced by a higher baseline oral intake (p = 0.02). Weaning off PS was influenced by the presence of colon (p = 0.04), a lower PS volume (p = 0.03) and a higher oral intake (p = 0.01). There were no differences based on age, bowel length or SBS-IF causes. CONCLUSIONS: Our study confirms the effectiveness of teduglutide in reducing PS needs in SBS-IF patients. We associated reduced parenteral support volume with baseline parenteral volume support, bowel anatomy, and oral intake. These findings underline the role of nutritional optimization when starting the treatment.

ESPEN guidelines on definitions and terminology of clinical nutrition.

BACKGROUND: A lack of agreement on definitions and terminology used for nutrition-related concepts and procedures limits the development of clinical nutrition practice and research. OBJECTIVE: This initiative aimed to reach a consensus for terminology for core nutritional concepts and procedures. METHODS: The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a consensus group of clinical scientists to perform a modified Delphi process that encompassed e-mail communication, face-to-face meetings, in-group ballots and an electronic ESPEN membership Delphi round. RESULTS: Five key areas related to clinical nutrition were identified: concepts; procedures; organisation; delivery; and products. One core concept of clinical nutrition is malnutrition/undernutrition, which includes disease-related malnutrition (DRM) with (eq. cachexia) and without inflammation, and malnutrition/undernutrition without disease, e.g. hunger-related malnutrition. Over-nutrition (overweight and obesity) is another core concept. Sarcopenia and frailty were agreed to be separate conditions often associated with malnutrition. Examples of nutritional procedures identified include screening for subjects at nutritional risk followed by a complete nutritional assessment. Hospital and care facility catering are the basic organizational forms for providing nutrition. Oral nutritional supplementation is the preferred way of nutrition therapy but if inadequate then other forms of medical nutrition therapy, i.e. enteral tube feeding and parenteral (intravenous) nutrition, becomes the major way of nutrient delivery. CONCLUSION: An agreement of basic nutritional terminology to be used in clinical practice, research, and the ESPEN guideline developments has been established. This terminology consensus may help to support future global consensus efforts and updates of classification systems such as the International Classification of Disease (ICD). The continuous growth of knowledge in all areas addressed in this statement will provide the foundation for future revisions.

Prevalence of immune-complex glomerulonephritides in dogs biopsied for suspected glomerular disease: 501 cases (2007-2012).

BACKGROUND: Glomerulonephropathies are common causes of kidney disease in dogs. OBJECTIVE: To determine the prevalence of immune-complex glomerulonephritis (ICGN) in North American dogs biopsied for suspected glomerular disease. ANIMALS: Renal biopsies (n = 733) submitted to the Texas Veterinary Renal Pathology Service between January 1, 2007 and December 31, 2012 were reviewed. Dogs were included if the biopsy was performed for suspected glomerular disease. METHODS: Specimens were evaluated by light microscopy (LM), immunofluorescence (IF), and transmission electron microscopy (TEM). Findings were retrospectively evaluated to categorize the diagnosis for each case. For the diagnosis of ICGN, TEM findings were considered conclusive when LM and IF were equivocal. RESULTS: Of the 501 dogs included in the study, 241 (48.1%) had ICGN; 103 (20.6%) had primary glomerulosclerosis; 76 (15.2%) had amyloidosis; 45 (9.0%) had nonimmune complex (IC) glomerulopathy; 24 (4.8%) had non-IC nephropathy; and, 12 (2.4%) had primary tubulointerstitial disease. Many (66/241; 27.4%) ICGN cases required TEM for definitive diagnosis, including 14 cases (5.8%) that were not suspected on LM. Of cases not diagnosed as ICGN, a substantial proportion (60/260; 23.1%) required TEM to rule out immune complex deposits, including 14 of 189 cases (7.4%) presumptively diagnosed as ICGN on LM. CONCLUSIONS AND CLINICAL IMPORTANCE: Approximately half of all dogs biopsied for suspected glomerular disease had conditions other than ICGN. Renal biopsy is needed to accurately categorize the underlying disease and direct appropriate treatment. Additionally, TEM and IF evaluations by experienced nephropathologists are necessary to obtain an accurate diagnosis in many cases.

Outcome of exfoliative rejection after isolated intestinal transplantation in an adult: case report.

A 34-year-old-man with short-bowel syndrome received an isolated small bowel graft. On postoperative day (POD) 11, ileal biopsy specimen demonstrated mild to moderate rejection that did not respond to corticosteroid bolus therapy. On POD 14, endoscopy and histologic examination revealed exfoliative rejection that was not controlled after 14 days of therapy with thymoglobulin. On POD 95, the patient underwent surgery again because of intestinal obstruction. The graft was removed 6 months after transplantation because of continuous severe abdominal pain with weight loss. After enterectomy, the patient developed multiple-organ failure and died on POD day 8. This case underlines the severity of exfoliative rejection and suggests that early enterectomy be performed when the diagnosis is made, before deterioration of clinical status and development of infectious and nutritional complications.

Esophageal varices in chronic intestinal insufficiency in absence of portal hypertension or liver cirrhosis: case report.

We report the case of a 62-year-old man with short-bowel syndrome, referred for intestinal transplantation, who had esophageal varices (EV) due to superior vena cava (SVC) thrombosis. Pretransplantation work-up revealed protein S deficiency. Results of liver function tests were normal. Upper endoscopy showed grade II to III EV in the upper and middle segments of the esophagus. Computed tomography demonstrated thrombosis of the jugular, subclavian, and SVC veins and marked collateral vessels in the chest. Transient elastography yielded normal findings. A liver biopsy specimen showed a normal aspect of the liver, without fibrosis or liver cirrhosis. Presence of EV in a patient with chronic intestinal insufficiency may be related to collateral venous circulation associated with SVC thrombosis in the absence of portal hypertension. In this situation, an isolated intestinal graft is indicated.

Consensus definition of sarcopenia, cachexia and pre-cachexia: joint document elaborated by Special Interest Groups (SIG) "cachexia-anorexia in chronic wasting diseases" and "nutrition in geriatrics".

Chronic diseases as well as aging are frequently associated with deterioration of nutritional status, loss muscle mass and function (i.e. sarcopenia), impaired quality of life and increased risk for morbidity and mortality. Although simple and effective tools for the accurate screening, diagnosis and treatment of malnutrition have been developed during the recent years, its prevalence still remains disappointingly high and its impact on morbidity, mortality and quality of life clinically significant. Based on these premises, the Special Interest Group (SIG) on cachexia-anorexia in chronic wasting diseases was created within ESPEN with the aim of developing and spreading the knowledge on the basic and clinical aspects of cachexia and anorexia as well as of increasing the awareness of cachexia among health professionals and care givers. The definition, the assessment and the staging of cachexia, were identified as a priority by the SIG. This consensus paper reports the definition of cachexia, pre-cachexia and sarcopenia as well as the criteria for the differentiation between cachexia and other conditions associated with sarcopenia, which have been developed in cooperation with the ESPEN SIG on nutrition in geriatrics.

[Epidemiological link between eating habits and cancer: the example of colorectal cancer]. / Lien épidémiologique entre comportement alimentaire et cancer: exemple du cancer colorectal.

One million people worldwide are affected by colorectal cancer (CRC) every year, resulting in 500,000 deaths. Incidence rate varies widely according to areas. It has been much more common in high-income countries. This trend begins to be reversed, with a stabilization of incidence rates in high-income countries and a dramatic increase in developing regions. CRC increase seems to overlap with the increasing level of urbanization in the latter. In the eighties, Doll and Peto already reported that 80% of cancer mortality was avoidable, particularly for CRC for which environmental influence is dominating. Observational studies have reported that migrants tended to reach similar CRC incidence levels that those of natives in the host country. An estimated 60% drop of all CRC cases could be obtained provided eating habits are modified, since these seem to be the main cause of incidence variations. Over the last ten years, many epidemiological studies and meta-analyses have been conducted. However, this abundant literature gave contradictory results. Therefore, in 1997, two groups of experts: the World Cancer Research Fund (WCRF) and the American Institute of Cancer Research (AICR), considered drafting a report on the correlation between diet and cancer a necessity. This systematic literature review, updated in 2007, established that red meat, processed meat and alcohol increase the risk of CRC. Conversely fibers, milk and calcium probably protect against CRC. Considering the most important prospective studies, randomised trials and the 2nd WCRF's report, our article aims at reviewing the evidences about diet and CRC.

Fatigue is associated with high circulating leptin levels in chronic hepatitis C.

BACKGROUND AND AIMS: Fatigue is a frequent and disabling symptom reported by patients with chronic hepatitis C (CHC). Its mechanism is poorly understood. Recent attention has focused on the role of leptin and energy expenditure in CHC. Our aims were to analyse fatigue in CHC and to determine its relationship with disease activity, resting energy expenditure (REE), circulating leptin, and tumour necrosis factor alpha (TNF-alpha). METHODS: Seventy eight CHC patients, 22 healthy controls, and 13 primary biliary cirrhosis (PBC) patients underwent measurements of REE, body composition, leptin, and TNF-alpha. All subjects completed the fatigue impact scale (FIS) questionnaire. A liver biopsy and viral load measurements were performed in all patients. RESULTS: Thirty eight of 78 CHC patients considered fatigue the worst or initial symptom of their disease. The fatigue score of patients was significantly higher than that of controls (53.2 (40.1) v 17.7 (16.9); p<0.0001) and was more pronounced in females (p=0.003). Leptin was increased significantly in CHC patients compared with controls (15.4 (20.7) v 6.4 (4.1) ng/ml; p<0.05). In CHC patients, the fatigue score correlated significantly with leptin corrected for fat mass (r=0.30, p=0.01). This correlation increased when the physical domain of fatigue was included (r=0.39, p=0.0009). Furthermore, a similar positive correlation was found in PBC patients (r=0.56, p=0.04). No correlation was found between fatigue and age, REE, liver function tests, viral load, or the METAVIR score in CHC patients. CONCLUSIONS: Fatigue is present in CHC patients and is more pronounced in females. The FIS questionnaire is clinically relevant and may be useful for future therapeutic trials aimed at reducing fatigue. Fatigue may be partly mediated by leptin.

Outcome of patients treated with home enteral nutrition.

BACKGROUND: The aims of this study were to prospectively analyze the 1-month mortality and long-term outcome of home enteral nutrition (HEN) patients in order to determine the benefits of this treatment. METHODS: Between 1990 and 1996, 417 patients, aged 64 +/- 25 years, were discharged on HEN and followed up until December 31, 1998, when outcome was assessed, which allowed us to determine survival probabilities and conditions associated with survival. RESULTS: The mean duration of HEN was 242 +/- 494 days, with a 24- to 103-month follow-up. Probabilities of being alive at 1 month, 1 year, and 5 years were 80%, 41.7%, and 25%, respectively. Factors associated with death were dementia, neurologic disease, head and neck cancer, AIDS, and age over 70 years. A total of 5.5% of patients remained dependent on HEN, 32.6% resumed full oral nutrition, 20.2% of patients died during the first month on HEN, and 35% died after more than 1 month on HEN (219 +/- 257 days). A total of 6.7% of patients stopped HEN for other reasons. CONCLUSIONS: HEN provides well-tolerated long-term nutritional support in many patients. However, because of their likelihood of being old and the nature of the underlying disease, these patients as a group tend to have a modest prognosis. This calls for the determination of more accurate selection criteria, and the measurement of the impact of HEN on quality of life.

From single site to societal belief: the impact of pediatric oncology nursing research.

This review describes the evolution of pediatric oncology nursing research over the past 25 years. It highlights practice-changing contributions from single-site studies and from multisite trials and discusses strategies for interdisciplinary collaboration. Technological advances that will alter the way in which studies are conducted and findings are disseminated will influence the future of nursing research. Studies implemented by pediatric nurse researchers will continue to influence practice and change how we, and others, view the experience of childhood cancer.

Activation of retinoic acid receptor alpha is sufficient for full induction of retinoid responses in SK-BR-3 and T47D human breast cancer cells.

Retinoid signaling via retinoic acid (RA) and retinoid X receptors (RARs and RXRs) regulates mammary epithelial cell growth and differentiation. Loss of RAR-beta might represent an early event during breast carcinogenesis. Higher differentiated, estrogen-dependent, estrogen receptor (ER)-positive (ER+) mammary carcinoma cells have been found to contain relatively high levels of RAR-alpha and to be responsive to retinoids, whereas most undifferentiated, estrogen-independent, ER-negative (ER-) cells are characterized by low RAR-alpha expression and by retinoid resistance. In contrast, RAR-gamma is detectable at equal levels in both ER+ and ER- cells. In the present investigation, we directly examined the relative contribution of the distinct retinoid receptors to the retinoid response of breast cancer cells by comparing the effects of low concentrations of specific retinoids, which selectively activate individual receptor subtypes, on growth, cell cycle distribution, apoptosis, and on the autoregulation of RAR-alpha and RAR-gamma in ER- SK-BR-3 and ER+ T47D breast cancer cells. In vitro growth activity was determined by using a colorimetric cell viability assay and analysis of cell cycle distribution, and apoptosis was performed by flow cytometry of propidium iodide-stained or fluorescent Annexin V-labeled cells, respectively, whereas expression of RAR-alpha and RAR-gamma was determined by Northern blotting. Both cell lines are retinoid sensitive and express high amounts of RAR-alpha, RAR-gamma, and RXR-alpha. RAR-alpha-selective compounds (AM80 and AM580) inhibit cell growth, induce G1 arrest, stimulate apoptosis, and up-regulate RAR-alpha and RAR-gamma mRNA as efficiently as RAR/RXR-pan-reactive (9-cis RA) and RAR-pan-reactive retinoids (all-trans RA, TTNPB). Remarkably, an RAR-alpha antagonist (Ro 41-5253) not only blocks the RAR-alpha-selective agonists but also the pan-reactive compounds. In contrast, RAR-13-selective (CD417), RAR-gamma-selective (CD437/AHPN), and RXR-alpha-selective (Ro 25-7386) retinoids exert no effects on the examined parameters. Thus, our results support the idea that RAR-alpha is the crucial receptor mediating the biological effects during retinoid signaling in both ER- SK-BR-3 and ER+ T47D human breast cancer cells.

Quality of life in long-term home enteral nutrition patients.

BACKGROUND AND AIMS: Few data are available on the quality of life of home enteral nutrition (HEN) patients. This study was designed to assess both the quality of life of long-term HEN patients and the evolution of quality of life after initiation of HEN. METHODS: Quality of life-related parameters were analysed in 38 patients (24M, 14F) aged 56 +/- 5 years who had been on HEN for more than 2 months (mean 25 +/- 5 months). Patients or close relatives were asked to answer a subjective assessment questionnaire, and patients with normal consciousness (n+ 24) answered the self-administered SF-36 and EuroQol questionnaires. RESULTS: Since the initiation of HEN, patients had spent 1.9 +/- 0.5% of the time in the hospital, in 54% of cases because of HEN-related complications. Analysis of the generic questionnaires revealed poorer quality of life parameters in comparison to a general population, although better results were sometimes observed in younger patients (under 45 years), patients without cancer, and patients with more than one care-giver. Nevertheless, the patients' subjective assessment of the changes in their quality of life since beginning HEN was generally good, with most patients reporting improved or stable mental and physical well-being. CONCLUSIONS: Quality of life is poor in HEN patients, but subgroups of patients who score better in some quality of life dimensions can be identified. Most patients describe an improvement in their quality of life following the initiation of HEN that needs to be confirmed by a prospective study.

Virtual reality as a distraction intervention for older children receiving chemotherapy.

The purpose of this pilot study was to describe the perceived effectiveness and feasibility of using virtual reality (VR) as a distraction intervention for children, aged 10-17, receiving outpatient chemotherapy. Treatments for cancer are intensive and difficult to endure. Distraction interventions are effective because the individual concentrates on pleasant or interesting stimuli instead of focusing on unpleasant symptoms. VR is a computer-simulated technique allowing an individual to hear and feel stimuli that correspond with a visual image. Evaluation of the VR intervention demonstrated positive outcomes. Eighty-two percent of the children (n = 11) indicated the chemotherapy treatment with the VR was better than previous chemotherapy treatments. All subjects responded positively when asked if they would like to use the VR again. The intervention was easy to implement, did not require practice to be effective, and required minimal nursing time. Results from this pilot study suggest that VR as a distraction intervention has the potential to enhance positive clinical outcomes. This intervention warrants further investigation with both pediatric and adult populations.

Inhibition of proliferation and induction of apoptosis in soft tissue sarcoma cells by interferon-alpha and retinoids.

Uncontrolled proliferation and a defect of apoptosis constitute crucial elements in the development and progression of tumours. Among many other biological response modifiers known to influence these mechanisms, the efficacy of retinoids and interferons in the treatment of various malignant entities is currently matter of discussion. In the present study, we have investigated the effects of 9-cis-retinoic acid (9cRA), 13-cis-retinoic acid (13cRA), all-trans-retinoic acid (tRA) and interferon-alpha on proliferation and apoptosis of human soft tissue sarcoma (STS) cell lines HTB-82 (rhabdomyosarcoma), HTB-91 (fibrosarcoma), HTB-92 (liposarcoma), HTB-93 (synovial sarcoma) and HTB-94 (chondrosarcoma) in relation to p53 genotype as well as p53 expression. HTB-91, HTB-92 and HTB-94 STS cells exhibited mutant p53, whereas wild-type p53 was found in HTB-93 STS cells, and a normal p53 status in HTB-82 STS cells, carrying a silent point mutation only. Interferon-alpha, irrespective of p53 status, inhibited the proliferation of all five cell lines dose- and time-dependently. Similarly, 9cRA, 13cRA and tRA decreased the proliferation of HTB-82 and HTB-93 STS cells, whereas the proliferation of p53-mutated HTB-91, HTB-92 and HTB-94 STS cells remained unchanged. Furthermore, only 9cRA and tRA were capable of inducing apoptosis in HTB-82 and HTB-93 STS cells, whereas HTB-91, HTB-92 and HTB-94 STS cells did not undergo apoptosis under the influence of 9cRA or tRA. Retinoic acid receptor (RAR)-alpha and RAR-beta mRNA were not detectable by Northern blot analysis in the five STS cell lines, whereas mRNA for the universal retinoic acid receptor, RAR-gamma, was expressed in all STS cell lines indicating that retinoid resistance was not associated with a lack of RAR expression. Apoptosis was not induced by interferon-alpha or 13cRA in any of the five STS cell lines tested. Our results indicate that within the panel of tested STS cell lines, inhibition of proliferation and induction of apoptosis result from different mechanisms which differ in their dependence upon the presence of intact p53.

Expression of c-erbB-4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3.

Nuclear steroid/retinoid and memgbrane c-erbB receptor tyrosine kinase signaling control proliferation and differentiation of mammary epithelial cells. Recently, we reported that retinoic acids are efficient repressors of c-erbB-2 and -3, but not of c-erbB-1 gene expresson. Here we demonstrate that retinoid acid- mediated growth inhibition is accompanied with reduced expression of c-erbB-4/HER4 in T47D breast cancer cells as determined by FACS, Western, and RT-PCR. All-trans and 9-cis retinoic acid reduce c-erbB-4 expression to 30%-60% of control, depending on the concentration. Dexamethasone (Dex) is inactive on D3 (D3), in contrast, acts as a strong inducer, elevation more that twofold at the mRNA, but does not significantly affect cell growth. We concolude that retinoic acids are efficient growth inhibitors and repressors of cell growth and c-erbB-4, whereas D3 represents a highly efficient inducer of c-erbB-4 expression with affecting cell proliferation.

Involvement of nuclear steroid/thyroid/retinoid receptors and of protein kinases in the regulation of growth and of c-erbB and retinoic acid receptor expression in MCF-7 breast cancer cells.

Nuclear steroid/thyroid/retinoid receptors and c-erbB membrane receptor tyrosine kinases control epithelial growth and differentiation. Retinoid receptors can dimerize with the vitamin D receptor, the glucocorticoid receptor or the thyroid receptor. Furthermore, multiple c-erbB receptor dimers have been identified. It has been shown that some of these receptor pathways communicate with each other via cross-connected regulatory networks. Molecular interactions between retinoid receptors or estrogen receptors (ER) and c-erbB-2, and between ER and retinoic acid receptor(RAR)-alpha have been reported. Here, we demonstrate the effects of steroids/thyroids/retinoids and of activators of protein kinase A (forskolin, Forsk) and C (12-O-tetradecanoylphorbol-13-acetate, TPA), on growth and expression of c-erbB and RARs in MCF-7 breast cancer cells, which contain high levels of RAR-alpha and -gamma, and which express significant amounts of c-erbB-2 and -3. All trans-retinoic acid (tRA), the anti-estrogen ICI 182 780 (ICI), Forsk and TPA reduced, whereas triiodothyronine and 17beta-estradiol (E2) stimulated cell growth. Flow cytometry revealed that tRA and E2 reduced c-erbB-2 and -3, whereas tamoxifen, Forsk and TPA up-regulated c-erbB-2. c-erbB-3 was co-regulated with c-erbB-2. Northern analysis demonstrated that RAR-alpha was down-regulated by dexamethasone, ICI, and TPA, whereas vitamin D3 and E2 up-regulated RAR-alpha. RAR-gamma expression was less responsive to such treatment, being reduced only by ICI and Forsk. These data indicate that nuclear receptor and protein kinase signaling communicate with each other and control the expression of RARs and c-erbB receptors. Efficient growth control requires the coordinated interplay of both receptor systems.

Effects of virtual reality on symptom distress in children receiving chemotherapy.

This study tested the premise that virtual reality (VR) as a distraction intervention could mitigate chemotherapy-related symptom distress in children with cancer aged 10-17 years. Cancer treatments are intensive and difficult to endure. Distraction interventions are effective because the individual concentrates on pleasant or interesting stimuli instead of focusing on unpleasant symptoms. VR as a distraction intervention is both immersive and interactive. For this study the individual wore a Virtual IO(R) headset during a single intravenous chemotherapy treatment. Participants chose one of three commercially available, CD ROM-based scenarios: Magic Carpet, Sherlock Holmes Mystery, and Seventh Guest(R). An interrupted time series design with removed treatment was used to answer these research questions: (1) Is VR an effective distraction intervention for reducing chemotherapy-related symptom distress in children? and (2) Does VR have a lasting effect? The convenience sample consisted of 11 children receiving outpatient chemotherapy. The Symptom Distress Scale (SDS) and the State-Trait Anxiety Inventory for Children (STAIC-1) were used to measure the dependent variable of symptom distress. Repeated-measures ANOVA were used for data analysis. Data analysis of the SDS suggested that the VR intervention was effective at reducing the level of symptom distress immediately following the chemotherapy treatment (p <.10), but did not have a lasting effect. Analysis of the STAIC-1 demonstrated high levels of anxiety during the initial chemotherapy treatment that decreased during subsequent treatments. State anxiety levels were not influenced by the VR intervention. This study supports the application of VR as a distraction intervention.