Body composition and muscle strength at the end of ICU stay are associated with 1-year mortality, a prospective multicenter observational study.

BACKGROUND & AIMS: After a prolonged intensive care unit (ICU) stay patients experience increased mortality and morbidity. The primary aim of this study was to assess the prognostic value of nutritional status, body mass composition and muscle strength, as assessed by body mass index (BMI), bioelectrical impedance analysis (BIA), handgrip (HG) test, and that of the biological features to predict one-year survival at the end of a prolonged ICU stay. METHODS: This was a multicenter prospective observational study. Survivor patients older than 18 years with ICU length of stay >72 h were eligible for inclusion. BIA and HG were performed at the end of the ICU stay. Malnutrition was defined by BMI and fat-free mass index (FFMI). The primary endpoint was one-year mortality. Multivariable logistic regression was performed to determine parameters associated with mortality. RESULTS: 572 patients were included with a median age of 63 years [53.5; 71.1], BMI of 26.6 kg/m2 [22.8; 31.3], SAPS II score of 43 [31; 58], and ICU length of stay of 9 days [6; 15]. Malnutrition was observed in 142 (24.9%) patients. During the 1-year follow-up after discharge, 96 (18.5%) patients died. After adjustment, a low HG test score (aOR = 1.44 [1.11; 1.89], p = 0.01) was associated with 1-year mortality. Patients with low HG score, malnutrition, and Albuminemia <30 g/L had a one-year death rate of 41.4%. Conversely, patients with none of these parameters had a 1-year death rate of 4.1%. CONCLUSION: BIA to assess FFMI, HG and albuminemia at the end of ICU stay could be used to predict 1-year mortality. Their ability to identify patients eligible for a structured recovery program could be studied.

Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin.

Nutritional habits can have a significant impact on cardiovascular health and disease. This may also apply to cardiotoxicity caused as a frequent side effect of chemotherapeutic drugs, such as doxorubicin (DXR). The aim of this work was to analyze if diet, in particular creatine (Cr) supplementation, can modulate cardiac biochemical (energy status, oxidative damage and antioxidant capacity, DNA integrity, cell signaling) and functional parameters at baseline and upon DXR treatment. Here, male Wistar rats were fed for 4 weeks with either standard rodent diet (NORMAL), soy-based diet (SOY), or Cr-supplemented soy-based diet (SOY + Cr). Hearts were either freeze-clamped in situ or following ex vivo Langendorff perfusion without or with 25 µM DXR and after recording cardiac function. The diets had distinct cardiac effects. Soy-based diet (SOY vs. NORMAL) did not alter cardiac performance but increased phosphorylation of acetyl-CoA carboxylase (ACC), indicating activation of rather pro-catabolic AMP-activated protein kinase (AMPK) signaling, consistent with increased ADP/ATP ratios and lower lipid peroxidation. Creatine addition to the soy-based diet (SOY + Cr vs. SOY) slightly increased left ventricular developed pressure (LVDP) and contractility dp/dt, as measured at baseline in perfused heart, and resulted in activation of the rather pro-anabolic protein kinases Akt and ERK. Challenging perfused heart with DXR, as analyzed across all nutritional regimens, deteriorated most cardiac functional parameters and also altered activation of the AMPK, ERK, and Akt signaling pathways. Despite partial reprogramming of cell signaling and metabolism in the rat heart, diet did not modify the functional response to supraclinical DXR concentrations in the used acute cardiotoxicity model. However, the long-term effect of these diets on cardiac sensitivity to chronic and clinically relevant DXR doses remains to be established.

Prediction of all-cause mortality in haemodialysis patients using a Bayesian network.

BACKGROUND: All-cause mortality in haemodialysis (HD) is high, reaching 15.6% in the first year according to the European Renal Association. METHODS: A new clinical tool to predict all-cause mortality in HD patients is proposed. It uses a post hoc analysis of data from the prospective cohort study Photo-Graph V3. A total of 35 variables related to patient characteristics, laboratory values and treatments were used as predictors of all-cause mortality. The first step was to compare the results obtained using a logistic regression to those obtained by a Bayesian network. The second step aimed to increase the performance of the best prediction model using synthetic data. Finally, a compromise between performance and ergonomics was proposed by reducing the number of variables to be entered in the prediction tool. RESULTS: Among the 9010 HD patients included in the Photo-Graph V3 study, 4915 incident patients with known medical status at 2 years were analysed. All-cause mortality at 2 years was 34.1%. The Bayesian network provided the most reliable prediction. The final optimized models that used 14 variables had areas under the receiver operating characteristic curves of 0.78 ± 0.01, sensitivity of 72 ± 2%, specificity of 69 ± 2%, predictive positive value of 70 ± 1% and negative predictive value of 71 ± 2% for the prediction of all-cause mortality. CONCLUSIONS: Using artificial intelligence methods, a new clinical tool to predict all-cause mortality in incident HD patients is proposed. The latter can be used for research purposes before its external validation at: https://www.hed.cc/? a=twoyearsallcausemortalityhemod&n=2-years%20All-cause%20Mortality%20Hemodialysis.neta.

Relative prognostic impact of nutrition, anaemia, bone metabolism and cardiovascular comorbidities in elderly haemodialysis patients.

BACKGROUND: The prognostic impact of nutrition and chronic kidney disease (CKD) complications has already been described in elderly haemodialysis patients but their relative weights on risk of death remain uncertain. Using structural equation models (SEMs), we aimed to model a single variable for nutrition, each CKD complication and cardiovascular comorbidities to compare their relative impact on elderly haemodialysis patients' survival. METHODS: This prospective study recruited 3165 incident haemodialysis patients ≥75 years of age from 178 French dialysis units. Using SEMs, the following variables were computed: nutritional status, anaemia, mineral and bone disorder and cardiovascular comorbidities. Systolic blood pressure was also used in the analysis. Survival analyses used Poisson models. RESULTS: The population average age was 81.9 years (median follow-up 1.51 years, 35.5% deaths). All variables were significantly associated with mortality by univariate analysis. Nutritional status was the variable most strongly associated with mortality in the multivariate analysis, with a negative prognostic impact of low nutritional markers {incidence rate ratio [IRR] 1.42 per 1 standard deviation [SD] decrement [95% confidence interval (CI) 1.32-1.53]}. The 'cardiovascular comorbidities' variable was the second variable associated with mortality [IRR 1.19 per 1 SD increment (95% CI 1.11-1.27)]. A trend towards low intact parathyroid hormone and high serum calcium and low values of systolic blood pressure were also associated with poor survival. The variable 'anaemia' was not associated with survival. CONCLUSIONS: These findings should help physicians prioritize care in elderly haemodialysis patients with CKD complications, with special focus on nutritional status.

Achievement of 2009 and 2017 Kidney Disease: Improving Global Outcomes mineral and bone targets and survival in a French cohort of chronic kidney disease Stages 4 and 5 non-dialysis patients.

BACKGROUND: The aim of the third French Phosphorus and Calcium Observatory (Photo-Graphe® 3) was to assess the achievement of international Kidney Disease: Improving Global Outcomes (KDIGO) recommendations on optimal serum phosphate, calcium and parathyroid hormone (PTH) levels and possible associations with mortality in patients with chronic kidney disease (CKD). METHODS: This was a prospective, observational study conducted with nephrologists in France who were selected using a clustering approach. Adult patients with non-dialysis Stage 4 or 5 CKD and no kidney graft history were eligible. Data about clinical events, serum biochemistry and treatment were collected every 6 months for 2.5 years and 12 months thereafter. The Kaplan-Meier method was used for survival analysis and Cox proportional hazards model for identification of factors associated with survival. RESULTS: Overall, 566 CKD Stage 4 patients (men, 56%) and 153 CKD Stage 5 patients (men, 62%) were included. In Stage 4, only 14-15% patients achieved the three main 2009 KDIGO targets during the first 2 years and 22% at 2.5 years. In Stage 5 patients, the proportion remained <6% throughout. The percentages of patients achieving the three main 2017 KDIGO targets were slightly higher at each time point. Overall, 14% of Stage 4 and 10% of Stage 5 patients died in the observation period. Only age and haemoglobin level were significantly associated with risk of all-cause mortality. CONCLUSIONS: Few CKD patients achieved KDIGO mineral targets. Increased mortality risk was linked to older age and lower haemoglobin level, but not to serum calcium, phosphate or PTH targets.

Achievement of Kidney Disease: Improving Global Outcomes mineral and bone targets between 2010 and 2014 in incident dialysis patients in France: the Photo-Graphe3 study.

BACKGROUND: Abnormal serum phosphate, calcium and parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) undergoing haemodialysis have been associated with poor survival. The French Phosphorus and Calcium Observatory (Photo-Graphe® 3) aimed to estimate the percentage of CKD patients achieving the three Kidney Disease: Improving Global Outcomes (KDIGO) targets about optimal serum phosphate, calcium and PTH over a 3.5-year follow-up period. METHODS: This was a prospective, multicentre, epidemiological observational study conducted with nephrologists in France, selected using a clustering approach. Eligible patients were adults undergoing intermittent haemodialysis or haemodiafiltration therapy started within the preceding 12 months. Data about clinical events, serum biochemistry and treatment were collected once every 6 months for 2.5 years and 12 months thereafter. RESULTS: Overall, 9010 incident patients were included (men, 63%; median age, 71 years) of whom 7515 (83.4%) were treated by haemodialysis and 1495 (16.6%) by haemodiafiltration. None had a history of fracture or revascularization while 89 (1%) patients had a history of parathyroidectomy >6 months. Overall, 874 (10%) patients received a kidney graft, 2183 (24%) died and 1148 (13%) were lost to follow-up. The proportion achieving the three KDIGO targets increased significantly from 11% to 16% (P < 0.0001) until Year 2, but remained stable afterwards. The percentage of incident dialysis patients with normal serum phosphate (P < 0.0001) or normal serum calcium (P < 0.0001) levels increased significantly over time, while no significant change was observed for those with controlled PTH. CONCLUSION: Less than 20% of patients achieved the KDIGO recommendations although their proportion increased slightly over time.

Modulation of Starch Digestibility in Breakfast Cereals Consumed by Subjects with Metabolic Risk: Impact on Markers of Oxidative Stress and Inflammation during Fasting and the Postprandial Period.

SCOPE: Decreasing postprandial glycaemic excursions may have a beneficial effect on inflammatory and oxidative stress profiles. In this study, we investigated the impact of carbohydrate digestibility modulation per se, as a means of reducing the glycaemic response, on metabolic and inflammatory responses in subjects with metabolic risk factors. METHODS AND RESULTS: Twenty healthy subjects with metabolic risk consumed a cereal product either high in Slowly Digestible Starch (HSDS) or low in SDS (LSDS) at breakfast daily for 3 weeks, in a cross-over design. Following each 3-week session, postprandial glycaemia, insulinaemia, the lipid profile, inflammation and oxidative stress markers were assessed and compared to those induced by ingestion of a glucose solution (as a reference). The 2-h glycaemic and insulinaemic responses were significantly lower following the HSDS breakfast compared with the LSDS breakfast or glucose. No significant differences between the products were observed in terms of the lipid profile, C-reactive protein, IL-6 and tumour necrosis factor alpha. We observed a slight increase in fasting lipid peroxidation markers, including an increase in plasma malondialdehyde (MDA) and a decrease in whole blood glutathione (GSH), without significant alteration of urinary F2-isoprostanes or plasma glutathione peroxidase (GPx) activity. CONCLUSION: Consumption of HSDS products for 3 weeks significantly altered both postprandial glycaemia and insulinaemia, but was not sufficient to modify the inflammatory profile. Consumption of both cereal products was associated with a slightly higher fasting oxidative stress profile.

[Management of bone and mineral metabolism disorders before the dialysis stage remains still perfectible. Data from the French Phosphorus and Calcium Survey Photo-Graphe]. / La prise en charge des troubles du métabolisme minéral et osseux avant le stade de la dialyse reste encore perfectible. À partir des données de l'Observatoire national du métabolisme minéral et osseux Photo-Graphe.

Only limited data is available on the management of the chronic kidney disease-associated bone and mineral metabolism disorder (CKD-MBD) in the pre-dialysis stages of CKD in France. A better knowledge of current management habits could lead to an improvement in the implementation of international recommendations (KDIGO). The 3rd version of the French Phosphorus and Calcium Survey Photo-Graphe (Sanofi) included a cohort of CKD stages 4 and 5 patients, whose aim was to examine the prevalence of CKD-MBD and the quality of its management in patients under the care of 62 nephrologists from over 20 geographical regions in France. The study started in October 2011, i.e. one year after patient enrollment. We examined in particular the percentage of patients presenting with laboratory parameter abnormalities indicative of CKD-MBD who were not receiving adequate treatment. A total of 456 patients with CKD stage 4 and 154 with CKD stage 5 were studied. Their mean age was 72.9±14.2 years, and male/female ratio was 58/42. KDIGO targets of serum PTH for CKD stages 4 and 5 were not achieved in respectively 80 and 84% of the patients, for serum calcium in 8 and 22% and for serum phosphate in 12 and 46%. As a potential explanation, insufficient therapy was estimated to account for respectively 45 and 60% of insufficiently controlled secondary hyperparathyroidism, and for 36% of persistent hyperphosphatemia in stage 5. It should be noted that 55.5 and 57.5% of patients were receiving native vitamin D. In this national observatory, the management of CKD-MBD stages 4 and 5 appears suboptimal, especially as regards the control of secondary hyperparathyroidism, which remained untreated in nearly 50% of the patients. Hyperphosphatemia was also common and inadequately controlled in CKD stage 5. To improve the management of CKD-MBD, nephrologists need to be more aware of the importance of aiming for recommended laboratory targets and how this can be achieved.

Performance of bile aspiration plus brushing to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography.

BACKGROUND AND STUDY AIMS: Endobiliary brushing during endoscopic retrograde cholangiopancreatography (ERCP) is the main technique used to diagnose a malignant stricture, but has a poor sensitivity. This study evaluated the diagnostic performance of bile aspiration associated with biliary brushing during ERCP to diagnose a malignant stricture, compared to brushing alone. PATIENTS AND METHODS: Between January 2007 and December 2012, all consecutive patients undergoing ERCP to treat a biliary stricture were included. After a biliary sphincterotomy, 3 mL to 10 mL of bile was aspirated into the brush catheter and collected in a dry sterile tube before and after brushing (to yield three samples). Brushing was performed as commonly recommended. RESULTS: One hundred eleven patients (68 males, 43 females) were included; mean age 67 ±â€Š15.4 years. A final diagnosis of malignant stricture was established in 51 patients, including 43 cholangiocarcinomas; 60 patients had benign strictures. Specificity (Sp) and positive predictive values were 100% for all samples. The diagnostic performance of the three-sample combination of bile aspiration + brushing + bile aspiration was significantly greater than brushing alone (P = 0.004): sensitivity (Se) = 84.3 % vs. Se = 66.7 %. The three-sample combination gave a negative predictive value of 88.2 %, and a diagnostic accuracy of 92.8 %. When suspicious results were added to malignant results as positive results, the three-sample combination gave Sp = 91.7 % and Se = 94.1 %. CONCLUSIONS: In cases of biliary stricture, conducting bile aspiration before and after brushing significantly increased the ability to diagnose a malignant stricture with a sensitivity of 84.3 % (P = 0.004).

Multiphasic effects of blood pressure on survival in hemodialysis patients.

Dialysis patients exhibit an inverse, L- or U-shaped association between blood pressure and mortality risk, in contrast to the linear association in the general population. We prospectively studied 9333 hemodialysis patients in France, aiming to analyze associations between predialysis systolic, diastolic, and pulse pressure with all-cause mortality, cardiovascular mortality, and nonfatal cardiovascular endpoints for a median follow-up of 548 days. Blood pressure components were tested against outcomes in time-varying covariate linear and fractional polynomial Cox models. Changes throughout follow-up were analyzed with a joint model including both the time-varying covariate of sequential blood pressure and its slope over time. A U-shaped association of systolic blood pressure was found with all-cause mortality and of both systolic and diastolic blood pressure with cardiovascular mortality. There was an L-shaped association of diastolic blood pressure with all-cause mortality. The lowest hazard ratio of all-cause mortality was observed for a systolic blood pressure of 165 mm Hg, and of cardiovascular mortality for systolic/diastolic pressures of 157/90 mm Hg, substantially higher than currently recommended values for the general population. The 95% lower confidence interval was approximately 135/70 mm Hg. We found no significant correlation for either systolic, diastolic, or pulse pressure with myocardial infarction or nontraumatic amputations, but there were significant positive associations between systolic and pulse pressure with stroke (per 10-mm Hg increase: hazard ratios 1.15, 95% confidence interval 1.07 and 1.23; and 1.20, 1.11 and 1.31, respectively). Thus, whereas high pre-dialysis blood pressure is associated with stroke risk, low pre-dialysis blood pressure may be both harmful and a proxy for comorbid conditions leading to premature death.

Low parathyroid hormone status induced by high dialysate calcium is an independent risk factor for cardiovascular death in hemodialysis patients.

Here we studied a possible association between low parathyroid hormone (PTH) status and mortality in incident patients undergoing hemodialysis . A total of 1983 patients were included at baseline and prospectively followed for 24 months. Patients were classified according to their Kidney Disease: Improving Global Outcomes PTH status at baseline and at 12 months, and mortality evaluated at 12 to 24 months using adjusted Cox analysis. Factors potentially involved in PTH status variability between baseline and 12 months were analyzed. A decrease in serum PTH from normal or high to low values between baseline and 12 months was associated with significantly increased cardiovascular mortality at 12 to 24 months (hazard ratio, 2.03; 95% confidence interval, 1.22-3.36). For patients with high or normal baseline PTH levels, the main independent factor at 6 months for a decrease to low PTH levels at 12 months was high dialysate calcium (1.75 mmol/L), whereas prescription of non-calcium-based phosphate binders was associated with a lower risk of PTH decrease. In the high cardiovascular (CV) mortality risk subgroup of patients who acquired a low PTH status at 12 months, the main independent factor at 12 months associated with significant 12- to 24-month CV mortality was high dialysate calcium (odds ratio, 5.44; 95% CI, 2.52-11.75). Thus, patients with a serum PTH decrease to low values after 1 year of hemodialysis treatment are at high risk of short-term CV death. High dialysate calcium was an important contributor to PTH oversuppression, and continued use was associated with increased CV mortality.

[Changes in mineral and bone disorder management in a French cohort of hemodialysis patients between 2008 and 2012: The National Bone and Mineral Metabolism observatory (Photo-Graphe 2 and 3)]. / Évolution de la prise en charge des troubles minéraux et osseux des patients hémodialysés en France entre 2008 et 2012 : Observatoire national du métabolisme minéral et osseux.

INTRODUCTION: Chronic kidney disease progressively induces a disorder of mineral and bone metabolism (CKD-MBD) which also leads to cardiovascular abnormalities. Previous studies showed that only few hemodialysis patients had serum calcium, phosphate and parathyroid hormone levels within the K/DOQI (Kidney-Disease Outcomes Quality Initiative) targets of 2003. Our aim was to identify the impact of different therapeutic strategies and that of the KDIGO (Kidney-Disease: Improving Global Outcomes) targets of 2009 on the control of CKD-MBD. PATIENTS AND METHODS: The French calcium and phosphate observatory monitors the mineral metabolism of patients with CKD at the local, regional and national level every six months. We compared the data recorded in June 2008 (n=1914 patients) with those collected in October 2012 (n=2481) for patients aged 18 years or more, who started hemodialysis therapy within the last 12 months. RESULTS: As compared with 2008, in 2012 fewer patients had hyperphosphatemia (55.1 % versus 64.7 %), hypocalcemia (35.5 % versus 40.3 %) and hyperparathyroidism (9.8 % versus 10.1 %) according to the KDIGO guideline, and more had hypophosphatemia (9.6 % versus 6.5 %), hypercalcemia (3.9 % versus 2.2 %) and hypoparathyroidism (31.5 % versus 25.8 %) (P<0.001, P<0.001 and P=0.002 respectively for differences in serum phosphate, calcium and PTH levels). Mean (± standard deviation [SD]) serum 25 OH vitamin D levels increased by 1.6-fold, from 48.3±42.6 nmol/L in 2008 to 76.6±45.8 nmol/L in 2012. Between 2008 and 2012, the prescription of native vitamin D derivatives and sevelamer (HCl or carbonate) increased whereas that of cinacalcet, lanthanum carbonate, calcium-chelating agents and active vitamin D derivatives decreased. CONCLUSION: Despite a slight improvement of biochemical CKD-MBD parameters in the observation period only few patients reached the three KDIGO targets (11.5 % in 2012 versus 11.1 % in 2008).

Gut microbiota richness promotes its stability upon increased dietary fibre intake in healthy adults.

Gut microbiota richness and stability are important parameters in host-microbe symbiosis. Diet modification, notably using dietary fibres, might be a way to restore a high richness and stability in the gut microbiota. In this work, during a 6-week nutritional trial, 19 healthy adults consumed a basal diet supplemented with 10 or 40 g dietary fibre per day for 5 days, followed by 15-day washout periods. Fecal samples were analysed by a combination of 16S rRNA gene pyrosequencing, intestinal cell genotoxicity assay, metatranscriptomics sequencing approach and short-chain fatty analysis. This short-term change in the dietary fibre level did not have the same impact for all individuals but remained significant within each individual gut microbiota at genus level. Higher microbiota richness was associated with higher microbiota stability upon increased dietary fibre intake. Increasing fibre modulated the expression of numerous microbiota metabolic pathways such as glycan metabolism, with genes encoding carbohydrate-active enzymes active on fibre or host glycans. High microbial richness was also associated with high proportions of Prevotella and Coprococcus species and high levels of caproate and valerate. This study provides new insights on the role of gut microbial richness in healthy adults upon dietary changes and host microbes' interaction.

Nonspecific immunoglobulin replacement in lung transplantation recipients with hypogammaglobulinemia: a cohort study taking into account propensity score and immortal time bias.

BACKGROUND: After lung transplantation (LT), immunoglobulin (Ig) G plasma concentrations<6 g/L are common and correlate with an increased risk of chronic lung allograft dysfunction (CLAD) and a poorer survival. METHODS: We conducted an open substitution intervention with nonspecific intravenous Ig (IVIg), in all patients with IgG plasma less than 6 g/L post-LT in 54 of 84 consecutive recipients since 1998 who survived more than 3 months. Pre-LT and post-LT events were retrospectively analyzed. RESULTS: Both substituted and nonsubstituted groups demonstrated similar donor or recipient characteristics and events over a median follow-up of 2.8 years (Q1-Q3, 1.4-5.7], except for initial diagnosis with more chronic obstructive pulmonary disease patients and less cases of pulmonary arterial hypertension in NS group. Intravenous Ig substitution started 3.5 months (0.5-9.4) after transplantation and lasted 4.5 months after (1.0-17.7), mean cumulative dose was 52.8±47.7 g. In multivariate Cox regression model, hypogammaglobulinemic patients who were substituted with IVIg had actually a 5-year survival (hazard ratio, 0.63; 95% confidence interval, 0.26-1.49; P=0.29) and CLAD-free 5-year survival (hazard ratio, 0.51; 95% confidence interval, 0.15-1.67; P=0.27) really close to nonhypogammaglobulinemic and nonsubstituted patients. Complementary analysis using propensity score and time-dependent analysis showed that survival and CLAD-free survival were not different in both groups. CONCLUSION: Intravenous Ig post-LT achieved similar survival and CLAD-free survival in recipients with hypogammaglobulinemia as compared to those with normal IgG plasmatic rate. A randomized control trial is required to confirm benefic effects of IVIg and disentangle mechanisms, including protection from infections, acute cellular and humoral rejections in patients with hypogammaglobulinemia after LT.

Characteristics and outcomes of chronic pulmonary aspergillosis: a retrospective analysis of a tertiary hospital registry.

INTRODUCTION: Our objective was to investigate characteristics risk factors and outcomes of patients with chronic pulmonary aspergillosis (CPA). METHODS: The Aspergillosis Committee prospectively collected Aspergillus notifications from January 2000 to December 2011. A retrospective analysis of data was performed. RESULTS: Among 1614 notifications registered, 44 cases of CPA in non-immunocompromised patients were identified. The median age was 65 years (Q1-Q3: 54-75), the median body mass index (BMI) was 20 kg/m(2) (Q1-Q3: 16-22) and 15 had chronic obstructive pulmonary disease. All patients had a positive specific serum precipitin antibody titer. Radiological presentations were: cavitations [single n = 31 (70%); multiple n = 12 (27%)] containing mycetomas [n = 18 (41%)], consolidations [n = 19 (43%)], emphysema [n = 15 (34%)] and sequelae of mycobacterial infection [n = 10 (23%)]. The median duration of follow-up was 30 months (Q1-Q3: 14-55). The median duration of antifungal treatment was 6 months (Q1-Q3: 3-12). Outcomes were unfavorable in 14 patients, and 12 (27%) died. Analysis by multivariate Cox regression model with bootstrapping showed that a higher BMI and a lower Charlson index score were predictive of favorable evolution, hazard ratio (95% confidence interval): BMI (+1) = 0.83 (0.71-0.97), Charlson (+1) = 1.37 (1.01-1.85). When analyses were restricted to chronic CPA and chronic necrotizing pulmonary aspergillosis, the multivariate Cox regression model showed that both BMI and Charlson index score were not statistically significant. CONCLUSION: Our results provide data on clinical characteristics and outcomes of CPA emphasizing the role of preexisting chronic respiratory conditions and protective effect of preserved BMI and lower Charlson index score.

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.

A simple semipaced 3-minute chair rise test for routine exercise tolerance testing in COPD.

The functional work capacity of chronic obstructive pulmonary disease (COPD) patients is usually assessed with walk tests such as the 6-minute walk test (6MWT) or the shuttle test. Because these exercise modalities require a controlled environment which limits their use by pulmonologists and severely restricts their use among general practitioners, different modalities of a short (1 minute or less) sit-to-stand test were recently proposed. In this study, we evaluated a new modality of a semipaced 3-minute chair rise test (3CRT) in 40 patients with COPD, and compared the reproducibility of physiological responses and symptoms during the 3CRT and their interchangeability with the 6MWT. The results demonstrate that physiological variables, heart rate, pulse oxygen saturation, work done, and symptoms (Borg dyspnea and fatigue scores), during the 3CRT were highly reproducible, and that the physiological responses and symptoms obtained during the 3CRT and the 6MWT were interchangeable for most patients. Moreover, these preliminary data suggest that patients able to perform more than 50 rises during 3 minutes had no significant disability. The simplicity and ease of execution of the 3CRT will facilitate the assessment of exercise symptoms and disability in COPD patients during routine consultations with pulmonologists and general practitioners, and will thus contribute to the improved management of COPD patients.

Early resuscitation of dengue shock syndrome in children with hyperosmolar sodium-lactate: a randomized single-blind clinical trial of efficacy and safety.

INTRODUCTION: Dengue shock syndrome (DSS) fluid resuscitation by following the World Health Organization (WHO) guideline usually required large volumes of Ringer lactate (RL) that might induce secondary fluid overload. Our objective was to compare the effectiveness of the recommended volume of RL versus a smaller volume of a hypertonic sodium lactate solution (HSL) in children with DSS. The primary end point was to evaluate the effect of HSL on endothelial cell inflammation, assessed by soluble vascular cell adhesion molecule-1 (sVCAM-1) measurements. Secondarily, we considered the effectiveness of HSL in restoring hemodynamic fluid balance, acid-base status, and sodium and chloride balances, as well as in-hospital survival. METHODS: A prospective randomized single-blind clinical trial including 50 DSS children was conducted in the Pediatrics Department of Hasan Sadikin Hospital, Bandung, Indonesia. Only pediatric patients (2 to 14 years old) fulfilling the WHO criteria for DSS and new to resuscitation treatments were eligible. Patients were resuscitated with either HSL (5 ml/kg/BW in 15 minutes followed by 1 ml/kg/BW/h for 12 hours), or RL (20 ml/kg/BW in 15 minutes followed by decreasing doses of 10, 7, 5, and 3 ml/kg BW/h for 12 hours). RESULTS: In total, 50 patients were randomized and included in outcome and adverse-event analysis; 46 patients (8.2 ± 0.5 years; 24.9 ± 1.9 kg; mean ± SEM) completed the protocol and were fully analyzed (24 and 22 subjects in the HSL and RL groups, respectively). Baseline (prebolus) data were similar in both groups. Hemodynamic recovery, plasma expansion, clinical outcome, and survival rate were not significantly different in the two groups, whereas fluid accumulation was one third lower in the HSL than in the RL group. Moreover, HSL was responsible for a partial recovery from endothelial dysfunction, as indicated by the significant decrease in sVCAM-1. CONCLUSION: Similar hemodynamic shock recovery and plasma expansion were achieved in both groups despite much lower fluid intake and fluid accumulation in the HSL group. TRIAL REGISTRATION: ClinicalTrials.gov NCT00966628. Registered 26 August 2009.

Effects of a breakfast spread out over time on the food intake at lunch and the hormonal responses in obese men.

The effects of frequent eating on health and particularly on appetite and metabolism are unclear. We have previously shown that frequent eating decreased appetite and energy intake at the subsequent meal in lean men. In the present study, we tested the same pattern in obese subjects. Seventeen obese men participated in: (i) two sessions consisting of a breakfast consumed in one eating episode at T0 (F1), or in four isocaloric eating episodes at T0, T60, T120, and T180min (F4), followed by an ad libitum buffet (T240) in an experimental restaurant. Subjects rated their appetite throughout the sessions. (ii) two sessions consisting of the same breakfasts F1 and F4 in a Clinical Centre, followed by a standardized meal. Blood sampling was performed to study ghrelin, glucagon-like peptide-1 (GLP-1), and metabolic kinetics. Indirect calorimetry measurements were performed. After F4, at T240min, ghrelin concentration (P=0.03) and hunger ratings (P<0.001) were lower while GLP-1 concentration (P=0.006) and satiety ratings (P=0.02) were higher. In F4, subjects consumed at the buffet, less food in grams (P=0.04) and less energy from low energy dense foods (P=0.01), but total energy intakes were not different between conditions. In F4, the area under the curve was lower for insulin (P=0.02) and non-esterified fatty acids (NEFA) (P=0.03). Diet induced thermogenesis was reduced in F4 (P=0.03) between T0 and T240. Even if subjective and physiological data suggest a beneficial effect of frequent eating on appetite in obese men, no effect was demonstrated on energy intake. Moreover, the decrease in diet induced thermogenesis and lipolysis, reflected by NEFA profiles, could be deleterious on energy balance in the long run.