Multicentre, prospective, double-blind, randomised controlled clinical trial comparing different non-opioid analgesic combinations with morphine for postoperative analgesia: the OCTOPUS study.

BACKGROUND: Head-to-head comparisons of combinations of more than one non-opioid analgesic (NOA) with morphine alone, for postoperative analgesia, are lacking. The objective of this multicentre, randomised, double-blind controlled trial was to compare the morphine-sparing effects of different combinations of three NOAs-paracetamol (P), nefopam (N), and ketoprofen (K)-for postoperative analgesia. METHODS: Patients from 10 hospitals were randomised to one of eight groups: control (C) received saline as placebo, P, N, K, PN, PK, NK, and PNK. Treatments were given intravenously four times a day during the first 48 h after surgery, and morphine patient-controlled analgesia was used as rescue analgesia. The outcome measures were morphine consumption, pain scores, and morphine-related side-effects evaluated 24 and 48 h after surgery. RESULTS: Two hundred and thirty-seven patients undergoing a major surgical procedure were included between July 2013 and November 2016. Despite a failure to reach a calculated sample size, 24 h morphine consumption [median (inter-quartile range)] was significantly reduced in the PNK group [5 (1-11) mg] compared with either the C group [27 (11-42) mg; P<0.05] or the N group [21 (12-29) mg; P<0.05]. Results were similar 48 h after surgery. Patients experienced less pain in the PNK group compared with the C, N, and P groups. No difference was observed in the incidence of morphine-related side-effects. CONCLUSIONS: Combining three NOAs with morphine allows a significant morphine sparing for 48 h after surgery associated with superior analgesia the first 24 h when compared with morphine alone. CLINICAL TRIAL REGISTRATION: EudraCT: 2012-004219-30; NCT01882530.

Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a large European cohort.

There are both limited and conflicting data on the role of dietary fat and specific fatty acids in the development of pancreatic cancer. In this study, we investigated the association between plasma phospholipid fatty acids and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The fatty acid composition was measured by gas chromatography in plasma samples collected at recruitment from375 incident pancreatic cancer cases and375 matched controls. Associations of specific fatty acids with pancreatic cancer risk were evaluated using multivariable conditional logistic regression models with adjustment for established pancreatic cancer risk factors. Statistically significant inverse associations were found between pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98; ptrend = 0.036), n-3 polyunsaturated α-linolenic acid (ORT3-T1 = 0.60; 95%CI = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI = 0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13-7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend = 0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40; 95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity analyses. Our findings suggest that higher circulating levels of saturated fatty acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may be related to lower risk of pancreatic cancer. The influence of some fatty acids on the development of pancreatic cancer may be sex-specific and modulated by smoking.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Randomized phase II-III study of bevacizumab in combination with chemotherapy in previously untreated extensive small-cell lung cancer: results from the IFCT-0802 trial†.

BACKGROUND: This randomized phase II-III trial sought to evaluate the efficacy and safety of adding bevacizumab (Bev) following induction chemotherapy (CT) in extensive small-cell lung cancer (SCLC). PATIENTS AND METHODS: Enrolled SCLC patients received two induction cycles of CT. Responders were randomly assigned 1:1 to receive four additional cycles of CT alone or CT plus Bev (7.5 mg/kg), followed by single-agent Bev until progression or unacceptable toxicity. The primary end point was the percentage of patients for whom disease remained controlled (still in response) at the fourth cycle. RESULTS: In total, 147 patients were enrolled. Partial response was observed in 103 patients, 74 of whom were eligible for Bev and randomly assigned to the CT alone group (n = 37) or the CT plus Bev group (n = 37). Response assessment at the end of the fourth cycle showed that disease control did not differ between the two groups (89.2% versus 91.9% of patients remaining responders in CT alone versus CT plus Bev, respectively; Fisher's exact test: P = 1.00). Progression-free survival (PFS) since randomization did not significantly differ, with a median PFS of 5.5 months [95% confidence interval (CI) 4.9% to 6.0%] versus 5.3 months (95% CI 4.8% to 5.8%) in the CT alone and CT plus Bev groups, respectively [hazard ratio (HR) for CT alone: 1.1; 95% CI 0.7% to 1.7%; unadjusted P = 0.82]. Grade ≥2 hypertension and grade ≥3 thrombotic events were observed in 40% and 11% of patients, respectively, in the CT plus Bev group. Serum vascular endothelial growth factor (VEGF) and soluble VEGF receptor titrations failed to identify predictive biomarkers. CONCLUSION: Administering 7.5 mg/kg Bev after induction did not improve outcome in extensive SCLC patients.

Chronic natural killer lymphoproliferative disorders: characteristics of an international cohort of 70 patients.

BACKGROUND: The 2008 World Health Organization (WHO) classification distinguishes three entities among the large granular lymphocytic leukemia (LGL leukemia): T-cell LGL leukemia (T-LGL leukemia), aggressive natural killer (NK) cell leukemia, and chronic NK lymphoproliferative disorders (LPD), the later considered as a provisional entity. Only a few and small cohorts of chronic NK LPD have been published. PATIENTS AND METHODS: We report here clinicobiological features collected retrospectively from 70 cases of chronic NK LPD, and compared with those of T-LGL leukemia. RESULTS: There were no statistical differences between chronic NK LPD and T-LGL leukemia concerning median age [61 years (range 23-82 years)], organomegaly (26%), associated autoimmune diseases (24%), and associated hematological malignancies (11%). Patients with chronic NK LPD were significantly less symptomatic (49% versus 18%, P < 0.001) and the association with rheumatoid arthritis was more rarely observed (7% versus 17%, P = 0.03). The neutropenia (<0.5 × 10(9)/l) was less severe in chronic NK LPD (33% versus 61%, P < 0.001) without difference in the rate of recurrent infections. STAT3 mutation was detected in 12% of the cohort, which is lower than the frequency observed in T-LGL leukemia. Thirty-seven percent of the patients required specific therapy. Good results were obtained with cyclophosphamide. Overall and complete response rates were, respectively, 69% and 56%. Overall survival was 94% at 5 years. CONCLUSION: This study suggests very high similarities between chronic NK LPD and T-LGL leukemias. Since chronic NK LPD is still a provisional entity, our findings should be helpful when considering further revisions of the WHO classification.

Mupirocin/chlorexidine to prevent methicillin-resistant Staphylococcus aureus infections: post hoc analysis of a placebo-controlled, randomized trial using mupirocin/chlorhexidine and polymyxin/tobramycin for the prevention of acquired infections in intubated patients.

PURPOSE: The reduction in acquired infections (AI) due to methicillin-resistant Staphylococcus aureus (MRSA) with the mupirocin/chlorhexidine (M/C) decontamination regimen has not been well studied in intubated patients. We performed post hoc analysis of a prior trial to assess the impact of M/C on MRSA AI and colonization. METHODS: We conducted a multicenter, placebo-controlled, randomized, double-blind study with the primary aim to reduce all-cause AI. The two regimens used [topical polymyxin and tobramycin (P/T), nasal mupirocin with chlorhexidine body wash (M/C), or corresponding placebos for each regimen] were administered according to a 2 × 2 factorial design. Participants were intubated patients in the intensive care units of three French university hospitals. The patients enrolled in the study (n = 515) received either active P/T (n = 130), active M/C (n = 130), both active regimens (n = 129), or placebos only (n = 126) for the period of intubation and an additional 24 h. The incidence and incidence rates (per 1,000 study days) of MRSA AI were assessed. Due to the absence of a statistically significant interaction between the two regimens, analysis was performed at the margins by comparing all patient receiving M/C (n = 259) to all patients not receiving M/C (n = 256), and all patients receiving P/T (n = 259) to all patients not receiving P/T (n = 256). RESULTS: Incidence [odds ratio (OR) 0.39, 95 % confidence interval (CI) (0.16-0.96), P = 0.04] and incidence rates [incidence rate ratio (IRR) 0.41, 95 % CI 0.17-0.97, P = 0.05] of MRSA AI were significantly lower with the use of M/C. We also observed an increase in the incidence (OR 2.50, 95 % CI 1.01-6.15, P = 0.05) and the incidence rate (IRR 2.90, 95 % CI 1.20-8.03, P = 0.03) of MRSA AI with the use of P/T. CONCLUSION: Among our study cohort of intubated patients, the use of M/C significantly reduced MRSA AI.

Psychological impact of medical evacuation for ICU saturation in Covid-19-related ARDS patients.

PURPOSE: Psychological impact of Medical Evacuation (MEDEVAC) in Covid-19 patients is undetermined. The objectives were to evaluate: Post-traumatic Stress Disorder (PTSD) in MEDEVAC patients hospitalized in ICU for Covid-19-related acute respiratory distress syndrome (ARDS) compared to control group; anxiety, depression rates and outcomes in patients and PTSD in relatives. MATERIAL AND METHODS: This is a retrospective multicentric 1/1 paired cohort performed in 10 ICUs in the West of France. Evaluation was performed 18 months after discharge. Patients and closest relatives performed IES-R (Impact and Event Scale-Revised) and/or HADS (Hospital Anxiety and Depression Scale) scales. RESULTS: Twenty-six patients were included in each group. Patients were 64 ± 11 years old, with 83% male. We report 12 vs 20% of PTSD in control vs MEDEVAC groups (p = 0.7). Anxiety disorder affected 43.5 vs 28.0% (p = 0.26) and depression 12.5 vs 14.3% (p > 0.99) in control vs MEDEVAC groups. PTSD affects 33.3 vs 42.1% of closest relatives (p = 0.55). Ways of communication were adapted: video calls were more frequent in MEDEVAC patients (8.7 vs 60.9%, p < 0.01) whereas physical visits concerned more control group (45.8 vs 13.0%, p = 0.01). CONCLUSIONS: PTSD rate were similar between groups. Adaptive ways of communication, restricted visits and global uncertainties could explain the absence of differences.

Specific anchoring modes of two distinct dystrophin rod sub-domains interacting in phospholipid Langmuir films studied by atomic force microscopy and PM-IRRAS.

Dystrophin rod repeats 1-3 sub-domain binds to acidic phosphatidylserine in a small vesicle binding assay, while the repeats 20-24 sub-domain does not. In the present work, we studied the adsorption behaviour of both sub-domains at the air/liquid interface and at the air/lipid interface in a Langmuir trough in order to highlight differences in interfacial properties. The adsorption behaviour of the two proteins at the air/liquid interface shows that they display surface activity while maintaining their alpha-helical secondary structure as shown by PM-IRRAS. Strikingly, R20-24 needs to be highly hydrated even at the interface, while this is not the case for R1-3, indicating that the surface activity is dramatically higher for R1-3 than R20-24. Surface-pressure measurements, atomic force microscopy and PM-IRRAS are used in a Langmuir experiment with DOPC-DOPS monolayers at two different surface pressures, 20 mN/m and 30 mN/m. At the lower surface pressure, the proteins are adsorbed at the lipid film interface while maintaining its alpha-helical structure. After an increase of the surface pressure, R1-3 subsequently produces a stable film, while R20-24 induces a reorganization of the lipid film with a subsequent decrease of the surface pressure close to the initial value. AFM and PM-IRRAS show that R1-3 is present in high amounts at the interface, being arranged in clusters representing 3.3% of the surface at low pressure. By contrast, R20-24 is present at the interface in small amounts bound only by a few electrostatic residues to the lipid film while the major part of the molecule remains floating in the sub-phase. Then for R1-3, the electrostatic interaction between the proteins and the film is enhanced by hydrophobic interactions. At higher surface pressure, the number of protein clusters increases and becomes closer in both cases implying the electrostatic character of the binding. These results indicate that even if the repeats exhibit large structural similarities, their interfacial properties are highly contrasted by their differential anchor mode in the membrane. Our work provides strong support for distinct physiological roles for the spectrin-like repeats and may partly explain the effects of therapeutic replacement of dystrophin deficiency by minidystrophins.

Reduced-dose tacrolimus with mycophenolate mofetil vs. standard-dose tacrolimus in liver transplantation: a randomized study.

We conducted a multicenter randomized study in liver transplantation to compare standard-dose tacrolimus to reduced-dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post-transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety-five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37-0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49-0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29-0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced-dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full-dose tacrolimus in adult liver transplantation.

Galactosyl headgroup interactions control the molecular packing of wheat lipids in Langmuir films and in hydrated liquid-crystalline mesophases.

The behavior of the two major galactolipids of wheat endosperm, mono- (MGDG) and di-galactosyldiacylglycerol (DGDG) was studied in aqueous dispersion and at the air/liquid interface. The acyl chains of the pure galactolipids and their binary equimolar mixture are in the fluid or liquid expanded phase. SAXS measurements on liquid-crystalline mesophases associated with the electron density reconstructions show that the DGDG adopts a lamellar phase L(alpha) with parallel orientation of the headgroups with respect to the plane of the bilayer, whereas MGDG forms an inverse hexagonal phase H(II) with a specific organization of galactosyl headgroups. The equimolar mixture shows a different behavior from those previously described with formation of an Im3m cubic phase. In comparing monolayers composed of the pure galactolipids and their equimolar mixtures, PM-IRRAS spectra show significant differences in the optical properties and orientation of galactosyl groups with respect to the interface. Furthermore, Raman and FTIR spectroscopies show that the acyl chains of the galactolipid mixture are more ordered compared to those of the pure components. These results suggest strong interactions between MGDG and DGDG galactosyl headgroups and these specific physical properties of galactolipids are discussed in relation to their biological interest in wheat seed.

Ultrafast double-pulse parametric amplification for precision Ramsey metrology.

We demonstrate phase stable, mJ-level parametric amplification of pulse pairs originating from a Ti:Sapphire frequency comb laser. The amplifier-induced phase shift between the pulses has been determined interferometrically with an accuracy of approximately 10 mrad. Typical phase shifts are on the order of 50-200 mrad, depending on the operating conditions. The measured phase-relation can be as stable as 20 mrad rms (1/300(th) of an optical cycle). This makes the system suitable for Ramsey spectroscopy at short wavelengths by employing harmonic upconversion of the double-pulses in nonlinear media.

Radiofrequency ablation of stage IA non-small cell lung cancer in patients ineligible for surgery: results of a prospective multicenter phase II trial.

BACKGROUND: A prospective multicenter phase II trial to evaluate the survival outcomes of percutaneous radiofrequency ablation (RFA) for patients with stage IA non-small cell lung cancer (NSCLC), ineligible for surgery. METHODS: Patients with a biopsy-proven stage IA NSCLC, staging established by a positron emission tomography-computed tomography (PET-CT), were eligible. The primary objective was to evaluate the local control of RFA at 1-year. Secondary objectives were 1- and 3-year overall survival (OS), 3-year local control, lung function (prior to and 3 months after RFA) and quality of life (prior to and 1 month after RFA). RESULTS: Of the 42 patients (mean age 71.7 y) that were enrolled at six French cancer centers, 32 were eligible and assessable. Twenty-seven patients did not recur at 1 year corresponding to a local control rate of 84.38% (95% CI, [67.21-95.72]). The local control rate at 3 years was 81.25% (95% CI, [54.35-95.95]). The OS rate was 91.67% (95% CI, [77.53-98.25]) at 1 year and 58.33% (95% CI, [40.76-74.49]) at 3 years. The forced expiratory volume was stable in most patients apart from two, in whom we observed a 10% decrease. There was no significant change in the global health status or in the quality of life following RFA. CONCLUSION: RFA is an efficient treatment for medically inoperable stage IA NSCLC patients. RFA is well tolerated, does not adversely affect pulmonary function and the 3-year OS rate is comparable to that of stereotactic body radiotherapy, in similar patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01841060 registered in November 2008.

[G6PD deficiency in females with neonatal revelation. Report of four cases]. / Déficit en G6PD chez la fille à révélation néonatale. Revue de 4 cas cliniques.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human erythrocyte enzyme defect, estimated to affect approximately 4 million people worldwide. It is associated with severe neonatal hyperbilirubinemia, which may lead to bilirubin encephalopathy and kernicterus, and with hemolytic crisis. G6PD deficiency is an X-linked enzymopathy affecting hemizygous males, homozygous females, and also a subset of heterozygous females via chromosome X inactivation. We report four cases of female newborns with neonatal hyperbilirubinemia related to a G6PD deficiency and followed by the Centre national de référence en hémobiologie périnatale (CNRHP) from November 2013 to July 2014. Clinical and biological characteristics suggested G6PD deficiency (jaundice observed within the first 24h, severe hyperbilirubinemia, associated with regenerative hemolytic anemia, low response to phototherapy, ethnic origin of the parents from high-incident geographical regions). The family investigations revealed a deficit in G6PD in one of the parents who was unaware of this deficit until then. This article aims to make neonatologists and pediatricians aware of the need to search for an etiology for any severe hyperbilirubinemia and to raise G6PD deficiency in male and female newborns in case of hyperbilirubinemia with hemolysis.

Interaction of the third helix of Antennapedia homeodomain and a phospholipid monolayer, studied by ellipsometry and PM-IRRAS at the air-water interface.

The penetratin peptide, a 16 amino acid sequence extracted from Antennapedia homeodomain, is able to translocate across a neural cell membrane through an unknown mechanism, most likely a non-specific interaction with membrane lipids. Beyond its potential application as vector targeting small hydrophilic molecules and enabling them to reach a cell nucleus, this observation raises intriguing questions concerning the physico-chemistry of peptide-lipid interactions. Here we present a study of the role of lipid surface pressure and head charge on the mechanism of interaction. This was performed using optical techniques: surface infrared spectroscopy and ellipsometry, applied to a monolayer of phospholipids deposited at the air-water interface. Determination of the structure and orientation of peptides and lipids (separately or together) evidenced that electrostatic rather than amphiphilic interactions determine the peptide adsorption and its action on lipids.

Two-dimensional crystallization of a membrane protein on a detergent-resistant lipid monolayer.

Two-dimensional crystals of a membrane protein, the proton ATPase from plant plasma membranes, have been obtained by a new strategy based on the use of functionalized, fluorinated lipids spread at the air-water interface. Monolayers of the fluorinated lipids are stable even in the presence of high concentrations of various detergents as was established by ellipsometry measurements. A nickel functionalized fluorinated lipid was spread into a monolayer at the air-water interface. The overexpressed His-tagged ATPase solubilized by detergents was added to the subphase. 2D crystals of the membrane protein, embedded in a lipid bilayer, formed as the detergent was removed by adsorption. Electron microscopy indicated that the 2D crystals were single layers with dimensions of 10 microm or more. Image processing yielded a projection map at 9 A resolution, showing three well-separated domains of the membrane-embedded proton ATPase.

Prognosis of neutropenic patients admitted to the intensive care unit.

PURPOSE: The prognosis of critically ill cancer patients has improved recently. Controversies remain as regard to the specific prognosis impact of neutropenia in critically ill cancer patients. The primary objective of this study was to assess hospital outcome of critically ill neutropenic cancer patients admitted into the ICU. The secondary objective was to assess risk factors for unfavorable outcome in this population of patients and specific impact of neutropenia. METHODS: We performed a post hoc analysis of a prospectively collected database. The study was carried out in 17 university or university-affiliated centers in France and Belgium. Neutropenia was defined as a neutrophil count lower than 500/mm(3). RESULTS: Among the 1,011 patients admitted into the ICU during the study period 289 were neutropenic at the time of admission. Overall, 131 patients died during their hospital stay (hospital mortality 45.3 %). Four variables were associated with a poor outcome, namely allogeneic transplantation (OR 3.83; 95 % CI 1.75-8.35), need for mechanical ventilation (MV) (OR 6.57; 95 % CI 3.51-12.32), microbiological documentation (OR 2.33; CI 1.27-4.26), and need for renal replacement therapy (OR 2.77; 95 % CI 1.34-5.74). Two variables were associated with hospital survival, namely age younger than 70 (OR 0.22; 95 % CI 0.1-0.52) and neutropenic enterocolitis (OR 0.37; 95 % CI 0.15-0.9). A case-control analysis was also performed with patients of the initial database; after adjustment, neutropenia was not associated with hospital mortality (OR 1.27; 95 % CI 0.86-1.89). CONCLUSION: Hospital survival was closely associated with younger age and neutropenic enterocolitis. Conversely, need for conventional MV, for renal replacement therapy, and allogeneic hematopoietic stem cell transplantation (HSCT) were associated with poor outcome.

Acute metobromuron poisoning with severe associated methemoglobinemia. Identification of four metabolites in plasma and urine by LC-DAD, LC-ESI-MS, and LC-ESI-MS-MS.

A case of self poisoning with metobromuron, a urea derivative used as a herbicide, is reported. Severe methemoglobinemia observed at the admission (80%) disappeared only at day 11, and hemolysis appeared at day 4 and decreased slowly to day 12. Metobromuron was analyzed by liquid chromatography with diode-array detection. Initial plasma concentration and elimination half-life were 4.9 mg/L and 5 h, respectively. Several metabolites were also detected, and four of those were identified by liquid chromatography-electrospray mass spectrometry. Normetobromuron, bromophenylurea, and bromoacetanilide were detected in plasma, but only N-methyl bromophenylurea was detected in urine. Bromoacetanilide probably results from acetylation of the intermediate bromoaniline. Methemoglobinemia could result from metabolization of metobromuron to bromoaniline and bromoacetanilide.

Use of buserelin to induce ovulation in the cyclic mare.

Inducing ovulation in a cyclic mare is often necessary. For this purpose, hCG has been used commonly, but the response can be reduced after successive administrations. The aims of this study were to test the effectiveness of buserelin in hastening ovulation in estrus mares, and its influence on fertility; and to investigate the effect of treatment on LH secretion. Five crossover trials were designed to compare the effect of two treatments: buserelin (40 microg in 4 doses i.v. at 12 h intervals) vs placebo (Experiments 1 and 2); buserelin 40 microg (in 4 doses i.v.) vs 20 microg (Experiment 3); buserelin (4 doses of 20 microg i.v.) vs hCG (1 dose of 2,500 IU i.v.) (Experiment 4); or buserelin (3 doses of 13.3 microg at 6 h interval) vs hCG (Experiment 5). In Experiment 2, blood samples were taken hourly until ovulation, for LH measurements. In Experiment 1, buserelin treatment significantly hastened ovulation. Reduction of the dose by half (Experiment 3) did not alter the effectiveness. In Experiments 4 and 5, buserelin was as effective as hCG in inducing ovulation between 24 and 48 h after initiation of treatment. Buserelin treatment induced a rise in LH concentration during the 48 h period of the experiment, and LH concentrations before ovulation were significantly higher in buserelin treated cycles than in placebo cycles. These experiments demonstrated the usefulness of two new protocols of administration of buserelin, as an alternative to hCG for induction of ovulation. One hypothesis explaining the mechanism of action is that the persistant rise in LH concentration could modify the ratio of biological/immunological LH, as it occurs physiologically, thereby hastening ovulation.

Non-invasive continuous positive airway pressure in acute hypoxaemic respiratory failure--experience of an emergency department.

Non-invasive continuous positive airway pressure (CPAP) seems to decrease the need for intubation in patients with severe cardiogenic pulmonary oedema (CPO) in the intensive care unit. The goals of our study were to delineate indications for CPAP in the emergency department, and to confirm its usefulness in such a setting. We retrospectively assess the evolution of all patients ventilated under CPAP for an acute hypoxaemic respiratory failure over a 1-year period (n = 64 patients). Hypercarbia and respiratory acidosis were present in most patients with CPO (PaCO2 = 54.4+/-22.3 mmHg; pH = 7.27+/-0.13), according to respiratory exhaustion, although initial PaCO2 was low in the pneumonia group. There was a significant improvement of arterial blood gases after 1 hour of ventilation in the CPO group (PaO2 = 254.1+/-121.0 mmHg; PaCO2 = 44.0+/-12.6 mmHg; pH = 7.34+/-0.08; p < 0.0001 for both parameters). In the pneumonia group, oxygenation was also improved but with the persistence of a significant shunt (PaO2 = 157.6+/-84.4 mmHg). Fifty-four patients (84%) were considered as successfully ventilated under CPAP, with no need for intubation and a favourable evolution, mainly in the CPO group. No side effects were reported. In conclusion, CPAP is a useful and easy-to-use ventilatory device in the emergency department. It is now one of our first line treatments during prehospital and emergency care of patients with CPO.

Biphasic-flow induced ventilation allows simultaneous ventilation in several animals, using a single multiple output ventilator--a preliminary report.

Biphasic-flow induced ventilation (BiFIV) is a variable time-cycled tracheal gas insufflation mode, using a specific multiluminal endotracheal tube. Some recent studies have reported efficiency of this new ventilatory mode in experimental in vitro and in vivo settings. We hypothesized that this ventilatory mode could be able to deliver simultaneous efficient ventilation for several animals, using a single ventilator prototype. The study was performed in three groups of three domestic pigs with a normal lung compliance. Each pig was initially anaesthetized, intubated with the specific endotracheal tube, and ventilated with a conventional ventilatory device. The animals were then simultaneously ventilated under BiFIV, using a single ventilator prototype, for each group of three animals. Physiological parameters and arterial blood gases were recorded at each study phase. All animals but one survived the experiment. We did not observe any significant differences in arterial gas exchange, under both ventilatory modes. Oxygenation was as efficient for each three animals ventilated under BiFIV, using a single ventilator device, as under conventional ventilation, using three separate ventilators (PaO2 = 112+/-17 mmHg under conventional ventilation versus 115+/-16 mmHg under BiFIV). In conclusion, variable time-cycled tracheal gas insufflation may allow an efficient multiple ventilation on several animals, using a single multiple output ventilatory device, in a normal lung animal model. If validated on subsequent pathological models, it could thus be interesting in laboratory and/or mass casualty situations.