Bone mineral density at extremely low weight in patients with anorexia nervosa.

OBJECTIVE: Low bone mineral density (BMD) is a frequent and invalidating consequence of chronic undernourishment in patients with anorexia nervosa (AN). The aim of this study was to assess prevalence and clinic-biological correlates of low BMD and fractures in extremely undernourished inpatients with AN. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: This study included 97 extremely malnourished female inpatients with AN consecutively admitted over 2 years. Clinical-biological variables, history of fractures and BMD by dual-energy X-ray absorptiometry (DXA) were examined to find predictors of low BMD and fractures. RESULTS: The prevalence of low BMD was of 51% for lumbar spine and 38% for femoral neck. Z-scores were lower at lumbar spine (-2.2 ± 1.2 SD) than at femoral neck (-1.9 ± 0.9 SD) (P<.01). Fragility fractures were reported by 10% of patients. BMD was mainly predicted by FFM, illness duration, age at onset and restricting AN (P<.05). Fractures were predicted by sodium concentrations, femoral neck Z-score and illness duration (P<.03). CONCLUSION: Extremely severe patients with AN have high prevalence of low BMD, predicted by severity and chronicity of malnutrition.

Evaluation of muscle-skeletal strength and peak expiratory flow in severely malnourished inpatients with anorexia nervosa: A pilot study.

OBJECTIVES: Anorexia nervosa is a complex psychiatric disorder that can lead to specific somatic complications. Malnutrition is frequent and can involve a decrease of mobility, up to functional impotence, in individuals with extremely severe cases. The aim of this pilot study was to examine muscle strength and peak expiratory flow (PEF) in severely undernourished patients with anorexia nervosa at admission and after 5 wk of renutrition by tube feeding, and to find the clinical and biological correlates of muscle-strength impairment. METHODS: A prospective observational study was conducted over 6 mo. Manual muscle testing, measures of PEF, and clinical and biologic assessments were performed at baseline and after 5 wk of renutrition. RESULTS: Twenty-three extremely malnourished female participants (mean body mass index: 11.4 ± 1.3 kg/m2) were included. All participants had global impairment in muscle strength (manual muscle testing: 37.7 ± 7.7) and PEF (253.3 ± 60 mL/min) at admission. Muscle weakness was higher in axial than peripheral muscle groups (P < 0.01), with no significant difference between proximal and distal muscles (P > 0.05). Muscle strength at admission was significantly associated with severity of undernourishment (body mass index and albumin) and transaminitis (P < 0.05). At follow-up, musculoskeletal strength and PEF were significantly improved after partial weight recovery (P < 0.01). CONCLUSIONS: Extremely undernourished people with anorexia nervosa present a decrease of PEF and musculoskeletal strength predominant on axial muscles. Both are associated with severity of malnutrition and liver damage. Partial recovery was observed after 5 wk of enteral nutrition.

Heart and anorexia nervosa.

Anorexia nervosa, one of the more frequent and severe eating disorders, is a chronic psychiatric disease with potentially serious somatic consequences. This behavioral symptomatology leads to weight loss, undernutrition, and more or less severe-potentially life-threatening-somatic complications including respiratory, hepatic, digestive and cardiac features, electrolyte disturbances, endocrine and bone impairment, immunodepression, and related opportunistic infections. In this review, the authors report an overview of cardiac diseases in this disease.

What distinguish patients with compulsory treatment for severely undernourished anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a mental disorder potentially leading to severe malnutrition and life-threatening complications, with high mortality rates and dropouts from treatment. In the most severe cases, treatment refusal associated with acute nutritional disorders may require compulsory admission in specialised units. The aim of this study was to investigate clinical and nutritional parameters associated with the use of compulsory treatment for severely ill AN patients requiring intensive nutritional care. METHODS: This retrospective, single-centre study performed in a unit of specialised nutritional care compared severely undernourished inpatients, compulsorily admitted for AN, with a population of sex- and age-matched voluntarily admitted patients. Socio-demographic and clinical variables were collected for univariate comparison and logistic regression. RESULTS: Compulsory treatment in AN was mainly associated with lower socio-economic status (p < 0.01), history of lower weight (p < 0.05), more frequently prescribed psychotropic medication (p = 0.02), more previous admissions for AN, longer hospitalisations (p < 0.01) and binge eating/purging subtype (p = 0.02). Binge eating/purging subtype and the number of past admissions showed the strongest odds of compulsory treatment in multivariate analysis. CONCLUSION: The knowledge of factors associated with compulsory treatment may help practitioners of all fields to better evaluate its pertinence and indications in AN.

Five-year mortality of severely malnourished patients with chronic anorexia nervosa admitted to a medical unit.

OBJECTIVE: Anorexia nervosa (AN) is associated with one of the highest mortality rates of any psychiatric disorder but limited mortality data were reported for those with extremely severe malnutrition. This study aimed to estimate standardized mortality ratio (SMR), investigate predictive factors of mortality and causes of death among a sample of patients with AN admitted to a specialized clinical nutrition unit (CNU) because of extremely severe malnutrition. METHODS: Between 11/27/1997 and 01/15/2014, vital status was determined for 384 patients admitted for AN at the first time in the CNU. Sociodemographic, anamnestic, and clinical data were collected. We calculated the SMR. Univariate and multivariate Cox regression analyses were performed to identify mortality predictors. RESULTS: Crude mortality rate was 11.5%. (44 deaths) and SMR 15.9 [CI 95% (11.6-21.4)], 5.2 years post inpatient treatment. Mortality predictors at the time of hospitalization were as follows: older age, occurrence of an in-hospital suicide attempt, transfer to medical intensive care unit and the following somatic complications: frank anemia, dysnatremia, infectious and cardiac complications. Other predictors of mortality were: past or present history of discharge against medical advice, hematological comorbidities (not related to AN). A longer inpatient length of stay was a protective factor. CONCLUSION: Very severely malnourished patients with AN hospitalized in a medical unit because of extremely severe somatic issues have a medium-term mortality rate higher than the general population and even higher than patients in tertiary specialized ED units. This study highlights predictive factors of mortality that will help clinicians in recognizing and managing patients at risk of death.

Extremely severe anorexia nervosa: Hospital course of 354 adult patients in a clinical nutrition-eating disorders-unit.

BACKGROUND AND AIMS: The clinical nutrition-eating disorders-unit in Raymond Poincaré Hospital is a reference center for the management of severe malnutrition and its complications in patients with anorexia nervosa (AN). The purpose of this study is to specify socio-demographic, anamnesic and clinical characteristics of AN patients hospitalized for extreme malnutrition, to identify types and prevalence of medical complications presented during their hospitalization for refeeding and the evolution of patients nutritional status. METHODS: Demographic, clinical and paraclinical data of 354 severely malnourished AN patients were collected, during their first hospitalization in the unit, between November 1997 and January 2014, through medical records. The prevalence of medical complications was compared between the 2 AN subtypes (restricting and binging-purging). RESULTS: 339 patients were female and mean age was 28.7 ± 10.7 years old. Duration of AN was 9.5 ± 9 years, 173 (48.9%) patients had a restricting AN subtype. BMI at admission was 12.2 ± 1.6 kg/m2, 280 (79.3%) patients had already been hospitalized for AN in other hospitals before. Psychiatric comorbidities were present in 168 (47.5%) patients. Associated somatic comorbidities concerned 70 (19.8%) patients. Outcomes during hospitalization were marked by 4.1 ± 3.9 kg weight gain on 36.9 ± 30.5 days. Enteral nutrition was provided in 304 (85.9%) patients. Main medical complications during hospitalization were: anemia (79%), neutropenia (53.9%), hypertransaminasemia (53.7%), osteoporosis (46.3%), hypokalemia (39.5%), hypophosphatemia (26%), hypoglycemia (13.8%), infectious complications (24.3%), cardiac dysfunction (7.1%), and proven gelatinous bone marrow transformation (6.5%). Hypokalemia was more frequent in binging-purging subtype. Lympho-neutropenia and hypertransaminasemia were more frequent in restricting subtype. During their hospitalization, 35 (10%) patients were referred to medical intensive care unit and 5 patients died. CONCLUSIONS: AN patients hospitalized for severe malnutrition in a specialized clinical nutrition unit have severe and frequent medical complications. Psychiatric comorbidities are also frequent and could complicate medical care. A specialized and multidisciplinary management of these patients is therefore essential.

Echocardiographic abnormalities in 124 severely malnourished adult anorexia nervosa patients: frequency and relationship with body composition and biological features.

BACKGROUND: Anorexia Nervosa (AN) is a complex psychiatric disorder that can lead to specific somatic complications. Heart abnormalities are frequently reported, while their frequency and associated factors in severely malnourished AN patients remain poorly defined. OBJECTIVES: This study aimed to characterize echocardiographic abnormalities in severely malnourished AN patients and to assess associated clinical, biological and related body composition features. METHODS: Between January 2013 and January 2015, all severely malnourished adult patients with AN (Mental Disorders, 4th Edn.-DSM IVr) were included in a monocentric study performed in in a highly specialized AN inpatient unit. Electrocardiogram (ECG) and echocardiography were used to assess both heart rhythm and function. All inpatients underwent a Doppler echocardiography procedure after undergoing combined blood volume adjustment, micronutrients deficiencies supplementation and electrolyte disorders correction. Right Ventricular (RV) and Left Ventricular (LV) systolic and diastolic functions were collected and compared to 29 healthy normal subjects in a control group. RESULTS: One hundred and 24 patients (119 (96%) women, 5 (4%) men) with a mean age of 30.1 ± 11 years old and an average Body Mass Index (BMI) of 12 kg/m2 were included. Ninety patients (73%) had been diagnosed with AN Restrictive type (AN-R), 34 (27%) an AN Binge eating/Purging type (AN-BP). Eighteen patients (15%) disclosed an abnormal Left Ventricular Ejection Fraction (LVEF) (< 52% for male and < 54% for female). LVEF impairment was associated with AN-BP patients (p < 0.017) and hypertransaminasemia (AST and/or ALT ≥2 N) (p < 0.05). Left Ventricular mass (LV mass) and Left Ventricular End Diastolic Diameter (LVEDD) were significantly reduced in patients (p < 0.001, p < 0.001). Left and right ventricular tissue Doppler Imaging Velocities (TDI) peak were reduced in patients: Septal and Lateral LV Sm velocities peaks respectively 10 ± 2 cm/s (vs 14 ± 2 cm/s in controls, p < 0.001), 12 ± 3 cm/s (vs 16 ± 3 cm/s in controls, p < 0.001), basal RV Sm velocity peaks at 14 ± 3 cm/s (vs 19 ± 3 cm/s in controls, p < 0.001). Additionally, LV and RV diastolic velocity peaks were reduced: LV septal and lateral velocity peaks were respectively 13 ± 3 cm/s (vs 18 ± 2 cm/s p < 0.001), 12 ± 3 cm/s (vs 22 ± 4 cm/s, p < 0.001) and RV diastolic velocity peaks at 14 ± 3 cm/s (vs 21 ± 4 cm/s p < 0.001). LV diastolic velocity TDI peaks were significantly associated with hypertransaminasemia (p < 0.05) and tended to be associated with a low all body Fat-Free Mass Index (FFMI) (using Dual-energy X- ray Absorptiometry (DXA) (HOLOGICQDR 4500) (p = 0.056). Thirty-four patients (27%) had a pericardial effusion and were significantly associated with a decreased all body FFMI (p < 0.036). CONCLUSION: Heart abnormalities are frequent in malnourished patients with AN, particularly in AN-BP type. Both liver enzymes and body composition abnormalities tended to be associated with heart dysfunction (non-significant association). Prospective studies are needed to better characterize and describe the evolution of cardiac abnormalities during the refeeding period and subsequent weight restoration.

Micronutrients Deficiencies in 374 Severely Malnourished Anorexia Nervosa Inpatients.

INTRODUCTION: Anorexia nervosa (AN) is a complex psychiatric disorder, which can lead to specific somatic complications. Undernutrition is a major diagnostic criteria of AN and it can be associated with several micronutrients deficiencies. OBJECTIVES: This study aimed to determinate the prevalence of micronutrients deficiencies and to compare the differences between the two subtypes of AN (restricting type (AN-R) and binge-eating/purging type (AN-BP)). METHODS: We report a large retrospective, monocentric study of patients that were hospitalized in a highly specialized AN inpatient unit between January 2011 and August 2017 for severe malnutrition treatment in the context of anorexia nervosa. RESULTS: Three hundred and seventy-four patients were included, at inclusion, with a mean Body Mass Index (BMI) of 12.5 ± 1.7 kg/m². Zinc had the highest deficiency prevalence 64.3%, followed by vitamin D (54.2%), copper (37.1%), selenium (20.5%), vitamin B1 (15%), vitamin B12 (4.7%), and vitamin B9 (8.9%). Patients with AN-BP type had longer disease duration history, were older, and had a lower left ventricular ejection fraction (LVEF) (p < 0.001, p = 0.029, p = 0.009) when compared with AN-R type patients who, instead, had significantly higher Alanine Aminotransferase (ALT) and Brain Natriuretic Peptide (BNP) levels (p < 0.001, p < 0.021). In the AN-BP subgroup, as compared to AN-R, lower selenium (p < 0.001) and vitamin B12 plasma concentration (p < 0.036) was observed, whereas lower copper plasma concentration was observed in patients with AN-R type (p < 0.022). No significant differences were observed for zinc, vitamin B9, vitamin D, and vitamin B1 concentrations between the two types of AN patients. CONCLUSION: Severely malnourished AN patients have many micronutrient deficiencies. Micronutrients status must be monitored and supplemented to prevent deficiency related complications and to improve nutritional status. Prospective studies are needed to explore the symptoms and consequences of each deficiency, which can aggravate the prognosis during recovery.

Impact of 3-week citrulline supplementation on postprandial protein metabolism in malnourished older patients: The Ciproage randomized controlled trial.

BACKGROUND: Citrulline (CIT), is not extracted by the splanchnic area, can stimulate muscle protein synthesis and could potentially find clinical applications in conditions involving low amino acid (AA) intake, such as in malnourished older subjects. OBJECTIVE: Our purpose was to research the effects of CIT supplementation on protein metabolism in particular on non-oxidative leucine disposal (NOLD, primary endpoint), and splanchnic extraction of amino acids in malnourished older patients. DESIGN: This prospective randomized multicenter study determined whole-body and liver protein synthesis, splanchnic protein metabolism and appendicular skeletal muscle mass (ASMM) in 24 malnourished older patients [80-92 years; 18 women and 6 men] in inpatient rehabilitation units. All received an oral dose of 10 g of CIT or an equimolar mixture of six non-essential amino acids (NEAAs), as isonitrogenous placebo, for 3 weeks. RESULTS: NOLD and albumin fractional synthesis rates were not different between the NEAA and CIT groups. Splanchnic extraction of dietary amino acid tended to decrease (p = 0.09) in the CIT group (45.2%) compared with the NEAA group (60.3%). Total differences in AA and NEAA area under the curves between fed-state and postabsorptive-state were significantly higher in the CIT than in the NEAA group. There were no significant differences for body mass index, fat mass (FM), lean mass (LM) or ASMM in the whole population except for a tendential decrease in FM for the citrulline group (p = 0.089). Compared with Day 1, lean mass and ASMM significantly increased (respectively p = 0.016 and p = 0.018) at Day 20 in CIT-treated women (mean respective increase of 1.7 kg and 1.1 kg), and fat mass significantly decreased (p = 0.001) at Day 20 in CIT-group women (mean decrease of 1.3 kg). CONCLUSIONS: Our results demonstrate that CIT supplementation has no effect on whole-body protein synthesis or liver protein synthesis in malnourished older subjects. However, CIT supplementation was associated with a higher systemic AA availability. In the subgroup of women, CIT supplementation increased LM and ASMM, and decreased FM.

Altered host-gut microbes symbiosis in severely malnourished anorexia nervosa (AN) patients undergoing enteral nutrition: An explicative factor of functional intestinal disorders?

BACKGROUND: Functional intestinal disorders (FIDs) are frequently observed in patients with anorexia nervosa (AN). Relationship between FIDs and a potential gut microbiota dysbiosis has been poorly explored. OBJECTIVE: We aimed to determine an association between FIDs severity and dysbiosis of the intestinal microbiota in a severely malnourished patient population with AN undergoing enteral nutrition. DESIGN: Faecal microbiota of AN (DSM IVr criteria) female inpatients were collected and compared to healthy controls based on 16S rRNA profiling. The severity of FIDs was evaluated in patients and healthy controls using Francis Score. RESULTS: Thirty-three patients (BMI: 11,7 ± 1,5; Age: 32 ± 12) and 22 healthy controls (BMI: 21 ± 2; age: 36 ± 12) were included. A marked dysbiosis was identified in AN patients compared to healthy controls (p = 0.03). Some potentially pathogenic bacterial genera (Klebsiella, Salmonella) were more abundant in AN patients whereas, other bacterial symbionts (Eubacterium and Roseburia) involved in immune balance were significantly less abundant in patients than controls. Severity of FIDs was strongly correlated with several microbial genera (r = -0.581 for an unknown genus belonging to Peptostreptococcaceae family; r = 0.392 for Dialister, r = 0.444 for Robinsoniella and r = 0.488 for Enterococcus). Other associations between dysbiosis, clinical and biological characteristics were identified including severity of undernutrition (BMI). CONCLUSION: Observed gut microbiota dysbiosis in malnourished patients with anorexia nervosa is correlated with the severity of FIDs and other metabolic disturbances, which strongly suggests an altered host-microbe symbiosis.

High-intensity exercise is associated with a better nutritional status in anorexia nervosa.

OBJECTIVE: Our aim is to investigate the links between duration and intensity of exercise and the nutritional status in terms of body composition in acute anorexia nervosa (AN) patients. METHOD: One hundred ninety-one hospitalized women suffering from AN were included. Exercise duration and intensity were assessed using a semistructured questionnaire. Body composition was measured using bioelectrical impedance. Linear multiple regression analyses were carried out using body mass index, fat-free mass index, and fat mass index as dependent variables and including systematically exercise duration, exercise intensity, and other confounding variables described in the literature that were significantly associated with each dependent variable in univariate analysis. RESULTS: A lower BMI was linked to lower exercise intensity, AN restrictive type, and presence of amenorrhea. A lower FFMI was linked to lower exercise intensity, older age, AN restrictive type, and premenarchal AN. Duration of exercise was not linked to the nutritional status. CONCLUSIONS: Exercising at higher intensity in AN is associated with a better nutritional status, thus, a better resistance to starvation. The impact of therapeutic physical activity sessions, adapted in terms of exercise intensity and patient's clinical status, should be evaluated during nutrition rehabilitation.

Negative role of malnutrition in cell-mediated immune response: Pneumocystis jirovecii pneumonia (PCP) in a severely malnourished, HIV-negative patient with anorexia nervosa.

It is generally acknowledged that malnutrition is a propensity factor for secondary infections in different clinical situations (malnutrition-associated infections in hospitalized patients and malnourished children in developing countries). However, it is not clear how malnutrition might facilitate the development of opportunistic infections in human immunodeficiency virus (HIV)-negative patients without a definite etiology (disease or treatment) of impaired cell-mediated immune response. We report here on a case of Pneumocystis jirovecii pneumonia in an HIV-negative patient suffering from anorexia nervosa with extreme malnutrition, which had a favorable outcome despite the severity of her respiratory failure. This report indicates the need for the early screening of nutritional status and rapid treatment initiation in patients with malnutrition, as well as the determination of opportunistic infections in the event of a low lymphocyte count.

Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial.

Background: Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL). Methods: Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29). Results: One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred. Conclusions: Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving.

New Insights in Anorexia Nervosa.

Anorexia nervosa (AN) is classically defined as a condition in which an abnormally low body weight is associated with an intense fear of gaining weight and distorted cognitions regarding weight, shape, and drive for thinness. This article reviews recent evidences from physiology, genetics, epigenetics, and brain imaging which allow to consider AN as an abnormality of reward pathways or an attempt to preserve mental homeostasis. Special emphasis is put on ghrelino-resistance and the importance of orexigenic peptides of the lateral hypothalamus, the gut microbiota and a dysimmune disorder of neuropeptide signaling. Physiological processes, secondary to underlying, and premorbid vulnerability factors-the "pondero-nutritional-feeding basements"- are also discussed.

Feasibility and results of pull-percutaneous endoscopic gastrostomy for enteral nutrition in adults with severe cerebral palsy.

BACKGROUND & AIMS: Eating and swallowing impairments often get worse as patients with severe cerebral palsy (CP) get older, creating increased demand for percutaneous endoscopic gastrostomy (PEG) tube placement. Here we investigated the feasibility, safety, adverse events (AEs) and outcomes of PEG in adult CP. METHODS: We performed a retrospective study of 26 consecutive severe adult (age: 28 [19-48] yrs) CP patients who underwent pull-PEG tube placement under general anesthesia between 2005 and 2012 (median follow-up: 23 [6-64] months) at the same tertiary hospital centre. RESULTS: The procedure was a technical success for 19 patients (BMI: 13.8 [10.7-21.4]) with (n = 11) or without (n = 8) previous respiratory disorder. Indications were mainly swallowing disorders (n = 14) and inadequate oral intake (n = 8). Early AEs were 7 transient oxygen needs, 3 local wound infections and 2 transient ileus. Long-term AEs were 9 non-severe gastrostomy incidents. There was no significant improvement in neurological status but respiratory function was improved in 6 patients and enteral nutrition enabled a significant median weight gain of 4.2 [1-8.8] kg (P < 0.01). Quality-of-life assessed by relatives and the healthcare team was improved in 13/16 and 13/15 cases respectively. AEs and outcomes did not differ significantly with previous respiratory disorder or nutritional status. CONCLUSIONS: PEG tube placement is feasible in adult CP, although the risk of failure is increased by anatomical specificities. Previous respiratory disorders and undernourishment did not increase AE rates or modify outcomes. There were positive changes over time for nutritional status and perceived quality-of-life, but no neurological improvement.

Four days a week or less on appropriate anti-HIV drug combinations provided long-term optimal maintenance in 94 patients: the ICCARRE project.

Short, intraweekly cycles of anti-HIV combinations have provided intermittent, effective therapy (on 48 patients) (1). The concept is now extended to 94 patients on treatment, 4 days per week or less, over a median of 2.7 discontinuous treatment years per patient. On suppressive combinations, 94 patients volunteered to treatment, 5 and 4 days per week, or reduced stepwise to 4, 3, 2, and 1 days per week in 94, 84, 66, and 12 patients, respectively, on various triple, standard, antiviral combinations, or nonregistered, quadruple, antiviral combinations. Ninety-four patients on treatment 4 days per week aggregated 165 intermittent treatment years; no viral breakthrough was observed over 87 average treatment weeks per patient, 63 of 94 having passed 2.5 intermittent treatment years on any of the antiviral combinations prescribed. On the hyperintermittent treatment of 3, 2, and 1 days per week, HIV RNA surged >50 copies, 4 weeks apart, in 18 instances (6.8 viral escapes/100 hyperdiscontinuous maintenance years). Viral escapes could have been a result of erratic adherence (EA) to regimen or follow-up (3 patients)--drug taken at half of the daily recommended dosage (8 patients) and/or overlooked archival-resistant HIVs from antecedent treatment failures (6 patients). Aside from the above circumstances, HIV unexpectedly rebounded in 3 patients on 2 days per week treatment and 1 patient on 1 day per week treatment, posting 2.2 intrinsic viral escapes/100 highly discontinuous treatment years. All 18 escapes were eventually reversed by 7 days per week salvage combinations, and 11 of 18 patients have been back for a second course of intermittent therapy, 4 days per week or less. Both cell-activation markers on the surface of T lymphocytes and cell-bound HIV DNA levels remained stable or declined. CD4/CD8 ratios rose to ≥1 in 35% of patients, whereas CD4 counts went ≥500/µl in 75%. These values were previously 7 and 40%, respectively, on 7 days per week therapy. In our aging, long, HIV-enduring, multitreated patient cohort, treatment 4 days per week and less over 421 intermittent treatment years reduced prescription medicines by 60%--equivalent to 3 drug-free/3 virus-free remission year per patient--actually sparing €3 million on just 94 patients at the cost of 2.2 intrinsic viral failure/100 hyperintermittent treatment years. At no risk of viral escape, maintenance therapy, 4 days per week, would quasiuniversally offer 40% cuts off of current overprescriptions.

Survival of patients with chronic respiratory failure on long-term oxygen therapy and or non-invasive ventilation at home.

BACKGROUND & AIMS: Chronic respiratory failure (CRF) is the common fate of respiratory diseases where systemic effects contribute to outcomes. In a prospective cohort of home-treated patients with CRF, we looked for predictors of long-term survival including respiratory, nutritional and inflammatory dimensions. METHODS: 637 stable outpatients with CRF, 397 men, 68 ± 11 years, on long-term oxygen therapy and/or non-invasive ventilation from 21 chest clinics were enrolled and followed over 53 ± 31 months. CRF resulted from Chronic Obstructive Pulmonary Disease (COPD) in 48.5%, restrictive disorders 32%, mixed (obstructive and restrictive patterns) respiratory failure 13.5%, bronchiectasis 6%. Demographic characteristics, smoking habits, underlying respiratory diseases, forced expiratory volume in one second (FEV1), forced vital capacity (FVC), arterial blood gases, 6-min walking distance (6MWD), hemoglobin, body mass index (BMI), serum albumin, transthyretin, C-reactive protein (CRP), history of respiratory assistance, antibiotic and oral corticosteroid use during the previous year were recorded. RESULTS: 322 deaths occurred during the follow-up. One-, five- and 8-year actuarial survival was 89%, 56% and 47%. By Cox univariate analysis, age, respiratory disease, PaO2, PaCO2, FEV1/FVC, BMI, 6MWD, activity score, type and length of home respiratory assistance, smoking habits, oral corticosteroid and antibiotic uses, albumin, transthyretin, hemoglobin and CRP levels were associated with survival. Multivariate analysis identified eight independent markers of survival: age, FEV1/FVC, PaO2, PaCO2, 6MWD, BMI, serum transthyretin, CRP ≥ 5 mg/l. CONCLUSIONS: In CRF, whatever the underlying diseases, besides the levels of obstructive ventilatory defect and gas exchange failure, 6MWD, BMI, serum transthyretin and CRP ≥ 5 mg/l predicted long-term survival identifying potential targets for nutritional rehabilitation.

Changes in weight after traumatic brain injury in adult patients: a longitudinal study.

BACKGROUND & AIMS: Although changes in weight have been reported after traumatic brain injury (TBI), their frequency and underlying factors are little known. Our aim was to determine the prevalence of weight changes and the associated factors during the recovery phase after TBI. METHODS: Longitudinal follow-up of adults with TBI. Multivariate analysis was carried out on weight change, demographic data, dysexecutive syndrome, eating behavior, physical activity, therapeutic classes and metabolic complications. RESULTS: 107 patients (81 males/26 females), age 36 ± 13 yrs, baseline BMI 23.3 ± 3.9, followed for 38 (8-66) months, were included. In intensive care, patients lost a mean 11 ± 6 kg. End of follow-up, mean BMI was not different to pre-TBI BMI, but patients could be categorized in 3 groups: stable (30%), loss (28%, -8 ± 7 kg) and gain (42%, +9 ± 6 kg). Sex, age, severity of TBI, intensive care weight loss, physical activity, therapeutic classes and the occurrence of metabolic syndrome did not differ between the groups. Factors related to weight gain were hyperphagia, OR 4.5 (IC95%, 1.6-12.1) and presence of a dysexecutive syndrome, OR 2.5 (IC95%, 1.03-6.3). Factors related to weight loss were hypophagia, OR 4.1 (IC95%, 1.5-10.9) and higher pre-TBI BMI, OR 4.9 (IC95%, 1.7-14.0). CONCLUSIONS: Over a median period of 38 months, 42% of TBI patients gained and 28% lost weight. Factors associated with these changes were the presence of a behavioral dysexecutive syndrome for weight gain, oral food intake and initial BMI, which were inversely associated with weight at end of follow-up. These findings highlight the importance of evaluating the time course of weight changes and providing specific nutritional care.

Symptoms of depression and anxiety in anorexia nervosa: links with plasma tryptophan and serotonin metabolism.

Depressive, anxiety and obsessive symptoms frequently co-occur with anorexia nervosa (AN). The relationship between these clinical manifestations and the biological changes caused by starvation is not well understood. It has been hypothesised that reduced availability of tryptophan (TRP) could reduce serotonin activity and thus trigger these comorbid symptoms. The aim of this study, during re-feeding in individuals with AN, was to analyse covariations across measures of nutritional status, depressive and anxiety symptoms, and peripheral serotonin markers. Depressive and anxiety symptoms, nutritional status and serotonin markers--whole blood serotonin content, plasma TRP and the ratio between TRP and large neutral amino acids--were assessed for 42 AN participants at admission to inpatient treatment and after re-feeding. Biological measures were compared to those obtained in 42 non-eating disordered subjects. For those with AN, psychological, nutritional and biological parameters improved significantly during hospitalisation. Levels of serotonin markers were significantly lower in the AN group compared to the control group, at admission and at discharge. Increase in the TRP/LNAA ratio was correlated with a decrease in depressive symptoms. In addition, there was a positive correlation between serotonin levels and symptoms of both anxiety and depression at discharge. We speculate that enhanced TRP availability during re-feeding, as a result of the increase in the TRP/LNAA ratio, could restore serotonin neurotransmission and lead to a decrease in depressive symptoms. The association between serotonin and anxiety and depressive symptoms would be consistent with numerous observations indicating abnormal functioning of the serotoninergic system in AN.