David Seguy

Pre-operative management is associated with low rate of post-operative morbidity in penetrating Crohn?s disease

Aliment Pharmacol Ther 2010; 32: 459–465

Better outcome of patients undergoing enteral tube feeding after myeloablative conditioning for allogeneic stem cell transplantation.

Background Parenteral nutrition (PN) is still widely preferred to enteral nutrition (EN) in malnourished patients undergoing allogeneic stem-cell transplantation (allo-SCT) after myeloablative conditioning (MAC). The purpose was to determine whether EN improves early outcome after MAC allo-SCT. Methods Early outcome was prospectively assessed in patients undergoing MAC allo-SCT. A total of 121 consecutive patients undergoing a first MAC allo-SCT for acute leukemia, myelodysplastic syndrome, or myeloproliferative syndrome were included. Patients who received cord blood were excluded. Enteral nutrition was systematically offered, although PN was provided when EN had been refused or was poorly tolerated. Among the patients, 94 received EN (EN group) and 27 did not (non-EN group). Overall survival (OS), cumulative incidence of engraftment and acute graft-versus-host disease (aGVHD) within the first 100 days after transplantation were studied. Because EN and PN treatment assignments were not random, propensity score adjustments were performed on patient outcomes. Results Outcome was better in the EN group than in the non-EN group for OS (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.04–0.42; P=0.0008), neutrophil (HR, 2.07; 95% CI, 1.26–3.39; P=0.004), and platelet (HR, 1.93; 95% CI, 1.004–3.70; P=0.049) engraftments and aGVHD development (HR, 0.12; 95% CI, 0.04–0.39; P=0.0004). In Cox model analysis, EN demonstrated a protective effect (HR, 0.20; 95% CI, 0.05–0.77; P=0.019) on OS, whereas demonstrated a detrimental impact (HR, 4.18; 95% CI, 1.02–17.12; P=0.047). Enteral nutrition was found to be an independent factor in neutrophil engraftment (HR, 2.17; 95% CI, 1.24–3.81; P=0.007), whereas PN delayed platelet engraftment (HR, 0.57; 95% CI, 0.33–0.99; P=0.046). Enteral nutrition was the only factor that was protective against grades 3 to 4 aGVHD development (HR, 0.19; 95% CI, 0.05–0.72; P=0.01). Conclusions Routine use of EN is preferable to upfront PN in these patients.

Efficacy and tolerance of gastrostomy feeding in pediatric forms of neuromuscular diseases.

BACKGROUND Percutaneous endoscopic gastrostomy (PEG) is a simple and reliable method, but there are few data about its use in pediatric forms of neuromuscular diseases (NMD). The aim of this study was to evaluate the nutritional effects and tolerance of gastrostomy feeding in NMD patients. METHODS Twelve patients with NMD, ranging in age from 1 month to 25.5 years, underwent a gastrostomy placement (PEG, n = 11; surgical gastrostomy, n = 1) between January 1990 and December 2000. Diseases were muscular dystrophies (n = 5), infantile spinal muscular atrophies (n = 3), congenital myopathies (n = 3), and polyradiculoneuritis (n = 1). Height-for-age (Z(H/A)), weight-for-age (Z(W/A)), and weight-for-height (Z(W/H)) z scores were assessed at birth, at the time of gastrostomy placement, after a 6-month and 1-year follow-up, and at the end of follow-up. Complications that occurred during the gastrostomy feeding period were recorded. Comparisons of z scores at the different times were performed with repeated-measures analyses of variance. RESULTS Z(W/A) (p < .05) and Z(W/H) (p < .001) improved in the whole group after gastrostomy. For the 10 patients for whom follow-up was more than 1 year, Z(W/A) (p < .03) and Z(W/H) (p < .001) increased from the time of gastrostomy to the end of follow-up. Among 5 patients who had a gastroesophageal reflux diagnosed before gastrostomy placement, 3 had at least 1 episode of pneumonia and 2 died of respiratory distress caused by the worsening of NMD. No other major complication was encountered. CONCLUSIONS Gastrostomy feeding is well tolerated and results in an improvement of nutritional indices in NMD patients. Special care should be taken in patients with preexisting gastroesophageal reflux.

Growth hormone enhances fat-free mass and glutamine availability in patients with short-bowel syndrome: an ancillary double-blind, randomized crossover study

BACKGROUND Benefits of recombinant human growth hormone (rhGH) alone or combined with glutamine in patients with intestinal failure because of short-bowel syndrome remain controversial. OBJECTIVE We explored effects of rhGH on whole-body protein metabolism in patients with short-bowel syndrome with intestinal failure (SBS-IF) to gain insight into its mechanism of action. DESIGN Eight stable hyperphagic patients with severe SBS-IF received, in a double-blind, randomized crossover study, low-dose rhGH (0.05 mg · kg⁻¹ · d⁻¹) and a placebo for two 3-wk periods. Leucine and glutamine kinetics under fasting and fed conditions, fat-free mass (FFM), and serum insulin were determined on the final day of each treatment. RESULTS rhGH increased FFM and nonoxidative leucine disposal (NOLD; an index of protein synthesis) (P < 0.02), whereas FFM and NOLD were correlated in the fed state (r = 0.81, P = 0.015). With rhGH administration, leucine release from protein breakdown (an index of proteolysis) decreased in the fed compared with fasting states (P = 0.012), which was not observed with the placebo. However, the fast-to-fed difference in leucine release from protein breakdown was not significantly different between rhGH and placebo (P = 0.093). With rhGH, the intestinal absorption of leucine and glutamine increased (P = 0.036) and correlated with serum insulin (r = 0.91, P = 0.002). rhGH increased glutamine de novo synthesis (P < 0.02) and plasma concentrations (P < 0.03) in both fasting and fed states. CONCLUSIONS In SBS-IF patients, feeding fails to decrease proteolysis in contrast to what is physiologically observed in healthy subjects. rhGH enhances FFM through the stimulation of protein synthesis and might decrease proteolysis in response to feeding. Improvements in de novo synthesis and intestinal absorption increase glutamine availability over the physiologic range, suggesting that beneficial effects of rhGH in hyperphagic patients might be achieved without glutamine supplementation.

The CP-MST, a malnutrition screening tool for institutionalized adult cerebral palsy patients

BACKGROUND & AIMS Progress in management of cerebral palsy (CP) patients has helped to increase life expectancy, but has also revealed nutritional consequences of this disability. The aims of this study were to determine the prevalence of malnutrition in long-term-institutionalized adult patients with CP and to propose specific malnutrition screening tool. METHODS Practitioners at 15 specialized institutions hosting CP patients assessed their nutritional status and completed a binary questionnaire containing thirteen questions related to factors suspected of increasing malnutrition. Moderate malnutrition was defined as the following: loss of weight (%) ≥ 5 to <10 or BMI ≥ 16 to <18.5 or albuminemia (g/l) ≥ 30 to <35. Markers of malnutrition were identified by bivariate analysis (ANOVA and Chi-square). Stepwise factorial discriminant analysis was used to determine the best subset of parameters for use in computation of a screening score. RESULTS A total of 365 patients age 35.7 ± 9.0 years were identified. Malnutrition was severe in 25%, moderate in 33% and absent in 42% of cases. The four strongest factors associated with malnutrition were used to build a three-level malnutrition screening tool for CP adult patients (CP-MST) as follows: body weight < 40 kg (10 points), sitting position uncomfortable or impossible (4 points), partial or total help to feed (4 points) and suspicion of gastro-esophageal reflux (3 points), (P < 0.0001): A screening score higher than 10 points indicated high risk with malnutrition probability of 90%, and detected 37% of malnourished patients. Conversely, a score equal to 0 excluded severe malnutrition in 90% of cases. CONCLUSION In light of the fact that 58% of these patients were malnourished, the CP-MST would appear to be useful for detecting malnutrition, underlining the need for a multidisciplinary approach in CP patients.

Citrulline and Monocyte-Derived Macrophage Reactivity before Conditioning Predict Acute Graft-versus-Host Disease

During conditioning, intestinal damage induces microbial translocation which primes macrophage reactivity and leads to donor-derived T cell stimulation. Little is known about the role of intestinal health and macrophage reactivity before conditioning in the development of acute graft-versus-host disease (aGVHD) in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). We assessed (1) citrulline, a surrogate marker of functional enterocyte mass and (2) circulating monocyte-derived macrophage reactivity, before allo-HCT. Forty-seven consecutive patients were prospectively included. Citrulline levels from blood samples withdrawn 30 days before transplantation were assessed using liquid chromatography combined with mass spectrometry. Monocyte-derived macrophages were isolated and incubated with 5 pathogen-associated molecular patterns: lipopolysaccharide, PamCSK4, flagellin, muramyl dipeptide, and curdlan. Multiplex fluorescent immunoassay on culture supernatant assessed levels of TNF-α, IL-1β, IL-6, and IL-10 in each condition. Citrulline and cytokine levels were analyzed relatively to aGVHD onset within 100 days after transplantation. Citrulline levels were lower in the aGVHD group (n = 20) than in the no-aGVHD group (n = 27) (P = .005). Conversely, IL-6 and IL-10 were greater in aGVHD group, especially after curdlan stimulation (P = .005 and P = .012). Citrulline levels ≤20 µmol/L, IL-6 ≥ 332 pg/mL, and IL-10 ≥ 90 pg/mL were associated with aGVHD development (log-rank test, P = .002, P = .041, and P < .0001, respectively). In multivariate analysis, IL-10 ≥ 90 pg/mL, myeloablative conditioning, and citrulline ≤20 µmol/L remained independent factors of aGVHD development (hazard ratio [HR],  8.18, P = .0003; HR, 4.28, P = .006; and HR, 4.43, P = .01, respectively). Preconditioning citrulline and monocyte-derived macrophage reactivity are objective surrogate markers suitable to identify patients at risk of developing aGVHD. This work highlights the influence of preconditioning status in aGVHD development.

NutriCancer: A French observational multicentre cross-sectional study of malnutrition in elderly patients with cancer

OBJECTIVES To compare the prevalence of malnutrition and nutritional management between elderly (≥70years old) and younger patients (<70years) with cancer. PATIENTS AND METHODS This is a post-hoc analysis of NutriCancer 2012 study; a one-day cross-sectional nationwide survey conducted to assess malnutrition in adult patients with cancer in France. Patients diagnosed with cancer at the study date in both inpatient and outpatient settings were included. Data collection was performed by means of questionnaires completed by the physician, the patient and the caregiver. RESULTS This post-hoc analysis compared 578 elderly patients (27.6%) vs. 1517 younger patients (72.4%). There were significant differences in cancer localization between the groups particularly in gastrointestinal cancer (27% in younger patients vs. 42% in elderly), breast cancer (17% vs 8% in elderly) and oropharyngeal (15% vs. 9% in elderly). Weight loss was significantly more reported in the elderly than in younger patients (73.6% vs. 67.6%, p=0.009). Elderly patients were more frequently malnourished than younger patients (44.9% vs. 36.7%, p=0.0006). Food intake was comparable between the groups; however, physicians overestimated the food intake, particularly in the elderly. The malnutrition management was more frequently proposed in elderly, as dietary advice and oral nutritional supplements, than in younger patients; however, enteral nutrition was significantly less undertaken in the elderly. CONCLUSION Malnutrition is prevalent in elderly patients with cancer, and more frequent than in younger patients. There is a need for an early integration of the nutritional counselling in patients with cancer, and particularly in the elderly.

Immunoassay quantification of human insulin added to ternary parenteral nutrition containers: comparison of two methods

Adding insulin directly into infusion bags seems to be a useful method for controlling hyperglycemia in patients under ternary parenteral nutrition (TPN). Its efficacy is assessed by glycemic monitoring but few data are available on insulin stability in this situation. Among the various methods for quantifying insulin levels in human serum, the immunoassay ones seemed potentially appropriate for a TPN admixture containing high lipid concentrations. We sought to identify and validate which of two immunoassay methods was the better to quantify human insulin and consequently be adapted to studying its stability in a TPN admixture. Two immunoassay methods to quantify recombinant human insulin were assessed in industrial TPN: an immunoradiometric assay (IRMA) and an immunoelectrochemiluminometric assay (IECMA). Validation trials for both methods were based on the accuracy profile method. Interference with immunometric assays due to the high lipidic content of TPN was eliminated through an improved preparation protocol using a bovine serum albumin (BSA) diluted in phosphate buffer saline (PBS). The relative total error of IECMA varied from 1.74 to 4.52% while it varied from −0.32 to 8.37% with IRMA. Only IECMA provided an accuracy profile with a 95% confidence interval of calculated-tolerance limits falling between the chosen acceptance limits (i.e., total error ≤±10%). IECMA combined with a BSA dilution is a simple and semi-automatic method that provides an accurate quantification of human insulin in a TPN admixture without any interference from lipids.

Are Upper-Body Axial Symptoms a Feature of Early Parkinson's Disease?

Background Axial disorders are considered to appear late in the course of Parkinson’s disease (PD). The associated impact on quality of life (QoL) and survival and the lack of an effective treatment mean that understanding and treating axial disorders is a key challenge. However, upper-body axial disorders (namely dysarthria, swallowing and breathing disorders) have never been prospectively assessed in early-stage PD patients. Objectives To characterize upper-body axial symptoms and QoL in consecutive patients with early-stage PD. Methods We prospectively enrolled 66 consecutive patients with early-stage PD (less than 3 years of disease progression) and assessed dysarthria, dysphagia and respiratory function (relative to 36 controls) using both objective and patient-reported outcomes. Results The mean disease duration was 1.26 years and the mean UPDRS motor score was 19.4 out of 108. 74% of the patients presented slight dysarthria (primarily dysprosodia). Men appeared to be more severely affected (i.e. dysphonia). This dysfunction was strongly correlated with low swallowing speed (despite the absence of complaints about dysphagia), respiratory insufficiency and poor QoL. Videofluorography showed that oral-phase swallowing disorders affected 60% of the 31 tested patients and that pharyngeal-phase disorders affected 21%. 24% of the patients reported occasional dyspnea, which was correlated with anxiety in women but not in men. Marked diaphragmatic dysfunction was suspected in 42% of the patients (predominantly in men). Conclusion Upper body axial symptoms were frequent in men with early-stage PD, whereas women presented worst non-motor impairments. New assessment methods are required because currently available tools do not reliably detect these upper-body axial disorders.

Place du diététicien dans l’équipe de soutien nutritionnel : évolution d’une profession

Resume Soulignee il y a pres de 30 ans, la denutrition a l’hopital reste un probleme majeur de sante publique qui touche 30 % a 50 % des patients a l’admission. La circulaire DHOS/E 1 n° 2002-186 du 29 mars 2002, en recommandant la mise en place au sein des centres hospitaliers de Comites de Liaison Alimentation Nutrition (CLAN) et d’unites de nutrition clinique, concretise les efforts engages ces dix dernieres annees en matiere d’alimentation-nutrition et de demarche d’accreditation des etablissements de sante. Le dieteticien, jusqu’alors garant de la qualite des prestations alimentation et dietetique, est egalement amene a jouer un role central, au sein de l’unite transversale de nutrition clinique, dans le depistage et la prise en charge de la denutrition. Cependant, sa formation initiale comme son statut actuel ne lui permettent pas d’aborder cette evolution de sa profession dans les meilleures conditions. L’actualisation de sa formation et la redefinition de ses missions semblent indispensables pour repondre aux exigences actuelles et ce d’autant que la prise en charge de la denutrition a l’hopital devient desormais, grâce a cette circulaire, une recommandation legale.