Unprecedented heat-related deaths during the 2003 heat wave in Paris: consequences on emergency departments

In August 2003, France sustained an unprecedented heat wave that resulted in 14,800 excess deaths. The consequences were maximal in the Paris area. The Assistance Publique–H?pitaux de Paris reported more than 2600 excess emergency department visits, 1900 excess hospital admissions, and 475 excess deaths despite a rapid organization. Indeed, simple preventice measures before hospital admissions are only able to reduce mortality which mostly occurred at home and in nursing homes.     

Influence of renal function on N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients admitted for dyspnoea in the Emergency Department: comparison with brain natriuretic peptide (BNP)

BACKGROUNDS: Renal dysfunction influences the optimum brain natriuretic peptide (BNP) threshold for a diagnosis of cardiac-related dyspnoea, but this has not been demonstrated for N-terminal pro-brain natriuretic peptide (NT-proBNP). We studied the influence of renal function on NT proBNP and BNP concentrations in dyspnoeic patients admitted by night to the Emergency Department (ED). METHODS: NT-proBNP, BNP, and creatinine levels were measured in blood samples collected routinely from 381 patients; estimated glomerular filtration rate (eGFR) was calculated. RESULTS: Cardiac-related dyspnoea was found in 115 patients (30.2%). NT-proBNP and BNP values were elevated in patients with cardiac-related dyspnoea (6823+/-6569 vs. 2716+/-4838 pg/ml, and 642+/-329 vs. 243+/-267 pg/ml, p<0.0001, respectively). Log-transformed NT-proBNP and BNP values were correlated to eGFR values. Mean NT-proBNP and BNP values stratified by ED diagnosis increased in line with eGFR categories, but in each category both peptide concentrations remained elevated in cardiac-related dyspnoea when compared with non-cardiac-related dyspnoea (p<0.05). NT-proBNP (and BNP) cut-off points rose as a function of eGFR categories: from 1360 (and 290) pg/ml in patients with eGFR 60-89 ml/min/1.73 m2, to 6550 (and 515) pg/ml in patients with eGFR 15-29 ml/min/1.73 m2. CONCLUSION: Renal function influences the optimal cut-off points of NT-proBNP and BNP for the diagnosis of cardiac-related dyspnoea.     

Rescue of early-stage myelodysplastic syndrome-deriving erythroid precursors by the ectopic expression of a dominant-negative form of FADD

Myelodysplastic syndromes (MDSs) are characterized by peripheral blood cytopenia including anemia. We have investigated the implication of the extrinsic pathway of apoptosis in MDS-ineffective erythropoiesis by in vitro expansion of erythroid precursors from early stage (low and intermediate-1 International Prognosis Scoring System [IPSS]) MDS, advanced stage (intermediate-2 IPSS) MDS, and control bone marrow samples. We have previously shown that Fas and its ligand were overexpressed in early stage MDS erythroid cells. Here, we show that caspase-8 activity is significantly increased, whereas the expression of death receptors other than Fas, including the type 1 receptor for tumor necrosis factor alpha (TNF-alpha) and the receptors for the TNF-related apoptosis-inducing ligand (TRAIL), DR4 and DR5, was normal. We also observed that the adapter Fas-associated death domain (FADD) was overexpressed in early stage MDS erythroid cells. Transduction of early stage MDS-derived CD34+ progenitors with a FADD-encoding construct increased apoptosis of erythroid cells and dramatically reduced erythroid burst-forming unit (BFU-E) growth. Transduction of a dominant-negative (dn) mutant of FADD inhibited caspase-8 activity and cell death and rescued BFU-E growth without abrogating erythroid differentiation. These results extend the observation that Fas-dependent activation of caspase-8 accounts for apoptosis of early stage MDS erythroid cells and demonstrate for the first time that FADD is a valuable target to correct ineffective erythropoiesis in these syndromes.     

Genome wide scan in a Flemish inflammatory bowel disease population: support for the IBD4 locus, population heterogeneity, and epistasis

BACKGROUND AND AIMS: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. METHODS: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohn's disease associated variants in the NOD2/CARD15 gene. RESULTS: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint non-parametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. CONCLUSION: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population.     

Pancreatic autoantibodies in inflammatory bowel disease

BACKGROUND: Autoantibodies against exocrine pancreas (PABs) have been reported to be specific for Crohn's disease (CD), albeit at a low prevalence (30%). We studied PABs in patients with inflammatory bowel disease (IBD), unaffected family members, and control subjects. METHODS: A Belgian study cohort of 575 subjects, including 289 IBD patients (CD, 169 patients; ulcerative colitis [UC], 120 patients), 108 unaffected first-degree relatives, 78 subjects with non-IBD gastrointestinal disorders (gastrointestinal control subjects [GIcos]), and 100 healthy control subjects (Hcos), were tested for PAB by a standardized indirect immunofluorescence method. RESULTS: The prevalence of PABs in this study cohort was 32% for CD, 23.3% for UC, and 22.2% for their unaffected family members (all P < 0.001), compared with 1.3% for GIcos and 0% for Hcos. Two staining patterns could be observed: an intracellular pattern (IC); and an extracellular pattern (EC). The EC was significantly more prevalent in CD patients compared with UC patients (P = 0.014), and higher titers of this pattern were found in CD patients (P = 0.01). Both PAB patterns were negatively associated with stricturing disease behavior of CD (P = 0.021). The IC was associated with familial CD (P = 0.0009) and familial UC (P = 0.0003). CONCLUSIONS: The prevalence of PAB found in CD patients in this study was similar to that cited in previous reports. In contrast to these reports, we also found an increased prevalence of PABs in patients with UC and in unaffected first-degree relatives of IBD patients. We observed two main staining patterns, both of which were present in IBD and were associated with specific phenotypes of the disease.     

Prevalence of HIV infection and risk behaviours among Montreal street youth

We aim to estimate HIV prevalence and associated risk factors among street youth in Montreal, Canada. We conducted a one-year cross-sectional anonymous study in 1995. We recruited youth aged 13-25 years meeting specific criteria for itinerancy through the 20 major Montreal street youth agencies. Participation included a structured interview and provision of an oral specimen for HIV testing. Among the 909 subjects studied, 99.3% had been sexually active, 25.9% had exchanged sex for money, gifts, drugs, a place to sleep, or other things; 31.8% reported anal sex; and 36.4% reported having ever injected drugs. Overall, HIV prevalence was 1.9% (1.1% in girls and 2.2% in boys). Multivariate logistic regression showed that being over 20 years of age (adjusted odds ratio (AOR) 7.09), having injected drugs (AOR 4.48), having engaged in prostitution (AOR 3.32), and being born outside Canada (AOR 4.41) were all independently associated with HIV infection.     

The thermogenic and metabolic effects of protein hydrolysate with or without a carbohydrate load in healthy male subjects

High-protein diets are beneficial in weight maintenance because of their satiating and thermogenic effects. These effects may be partly mediated by the hormonal effects of proteins. This study investigated the effect of soy protein hydrolysate (SPH) with and without a carbohydrate pre- and afterload on energy metabolism and hormonal secretion in 8 healthy nonobese subjects. In an additional trial, pea protein hydrolysate was compared to SPH, both with a carbohydrate afterload. The study had a single-blind crossover design. In all cases, 0.4 g protein and/or carbohydrate per kilogram of body weight was tested. Diet-induced thermogenesis (DIT) was measured by ventilated hood measurements, and postprandial blood samples were drawn over 3 hours. Soy protein hydrolysate consumption induced a higher DIT than a carbohydrate (CHO) load. Both conditions induced similar insulin responses. Soy protein hydrolysate induced a glucagon, but no glucose, response; whereas CHO induced a glucose, but no glucagon, response. Soy protein hydrolysate with a CHO pre- or afterload induced similar DIT and insulin responses. No glucose response was found when SPH preceded the CHO load. Total glucagon responses were similar with CHO as pre- and afterload, but time courses were different. Pea protein hydrolysate with a CHO afterload induced both higher insulin and glucagon responses (area under the curve) than SPH with CHO afterload, but DIT was similar in both conditions. In conclusion, this study shows that the larger DIT after protein than after CHO may be related to the glucagon response that is induced by protein but not by CHO; that the protein-induced DIT and glucagon response are not influenced by a CHO pre- or afterload; and that protein ingestion can fully prevent the plasma glucose increase associated with CHO when CHOs are ingested after proteins.     

Early high-dose erythropoietin therapy and hypothermia after out-of-hospital cardiac arrest: a matched control study

AIM: To test the possible neuroprotective effect of early high-dose erythropoietin-alpha (Epo-alpha) after out-of-hospital cardiac arrest (OHCA). METHODS: A matched control study. Following resuscitation with mild hypothermia after OHCA, participants received a first dose of Epo-alpha followed by four additional injections within 48 h (40,000 IU intravenously each injection). Plasma Epo-alpha levels were measured at different time points. Outcome and adverse events were assessed up to day 28 and were compared with those of matched-paired controls. RESULTS: In all 18 participants received Epo-alpha and were compared with 40 matched controls. Pharmacokinetic variables were similar to those previously reported for healthy people or for persons treated with usual dosages of Epo. At day 28, survival rates among the Epo-treated group and the controls (55% versus 47.5%, p=0.17) and rates of full neurological recovery (55% versus 37.5%) did not differ significantly. Incidences of thrombocytosis in the Epo-treated group and controls were 15% and 5%, respectively; an arterial vascular thrombosis was observed in one case (5%) from the Epo-treated cohort. CONCLUSIONS: Among victims of OHCA treated with Epo-alpha and hypothermia, we observed a high survival rate, with no minor cerebral sequels but potential haematological side effects. Future studies of Epo should pay particular attention to these findings.     

N-Terminal pro B-type natriuretic peptide testing for short-term prognosis in breathless older adults

Background

Amino-terminal pro–brain natriuretic peptide (NT-proBNP) is useful for the triage of patients with dyspnea. Our aim was to determine whether NT-proBNP levels could predict in-hospital outcome in breathless elderly patients.

Methods

At admission, NT-proBNP plasma concentrations were determined in 324 dyspneic patients aged 75 years and older. The association between NT-proBNP values and in-hospital mortality was assessed.

Results

Median NT-proBNP concentrations were not different in deceased patients (n = 43, 13%) compared to that of survivors (n = 281, 87%) (4354 vs 2499 pg/mL, respectively; P = .06). To predict in-hospital mortality, the optimum threshold of NT-proBNP was 3855 pg/mL, as defined by the receiver operating characteristic (ROC) curve, with a nonsignificant area under the ROC curve of 0.59. Mortality was significantly higher in patients (n = 139) with NT-proBNP levels 3855 pg/mL or higher (17.9% vs 9.7%, P = .045). After multivariate analysis, NT-proBNP level 3855 pg/mL or higher at admission was predictive of mortality (odds ratio, 2.41; 95% confidence interval, 1.02-5.68; P = .04).

Conclusion

NT-proBNP higher than 3855 pg/mL is associated with in-hospital mortality in patients aged 75 years and older admitted for dyspnea.