Search

Background: Patients evaluated in our emergency department (ED) often receive nonsteroidal anti-inflammatory drugs (NSAIDs) without any determination of their renal function, despite the known nephrotoxicity of NSAIDs. Guidelines recommend NSAID avoidance in patients with estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m 2 , and long-lasting therapy is not recommended in people with chronic kidney disease., Objective: We aimed to highlight the influence of a rapid measurement of the eGFR on NSAID prescriptions in patients at risk of impaired renal function using a point-of-care (POC) device. Our goal was to prevent the potential nephrotoxicity of NSAIDs by allowing the physicians to modify their treatments after eGFR determination, while avoiding a standard blood test for patients that would extend the duration of stay in the ED., Methods: We included 192 patients evaluated in the ED for minor trauma or injury, with an indication of treatment with NSAIDs and no known contraindication to NSAIDs. Emergency physicians were asked to register their intention to actually prescribe NSAIDs based on their clinical gestalt with specific regard to kidney function. Immediately after, the creatinine level was measured in capillary blood and eGFR was calculated using the POC device (StatSensor Creatinine; Nova Biomedical, Waltham, MA). Our physicians avoided NSAID prescriptions when eGFR was < 30 mL/min/1.73 m 2 , and prescribed a shorter NSAID regimen therapy in patient with eGFR < 45 mL/min/1.73 m 2 , with a reminder to assure hydration. The decision based on eGFR was compared with original clinician intention., Results: The clinicians intended to treat 164 patients with NSAIDs (group 1) and defer NSAIDs in 28 patients (group 2). In the first group, eGFR results supported no change in intended NSAID use in 144 patients, highlighted the need for a short regimen in 17 patients, and indicated contraindication to NSAIDs in 3 patients. In group 2, eGFR determination allowed prescription of NSAIDs in 21 patients, allowed utilization of NSAIDs with a short course in 5 patients, and supported the clinician decision to avoid NSAIDs in 2 patients., Conclusions: POC measurement of creatinine with eGFR estimation changed the prescription of NSAIDs in almost 25% of patients with previously unknown renal function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Despite the combined adjuvant treatment of radiotherapy plus chemotherapy with temozolomide (TMZ) followed by 6 cycles of temozolomide after surgery, the prognosis of patients with glioblastoma remains poor. We conducted a monocentric prospective study to explore the tolerance and potential efficacy of an early temozolomide cycle after surgery., Method: Patients with newly diagnosed glioblastoma (unmutated IDH1) and of poor prognosis (age>50 years, biopsy or partial resection or unmethylated MGMT promoter) were prospectively included from June 2014 to 2017. They all received a cycle of 5 days of temozolomide between surgery and the combined adjuvant treatment., Results: Twelve patients of median age 64.5 years (45-73) were included in the study. The median doses of temozolomide administered were respectively 265mg (225-300) for the early cycle; 130mg (110-150) for the concomitant treatment and 310mg (225-400) for the adjuvant one. Side effects during treatment were grade III lymphopenia, grade III neutropenia, fatigue and nausea/vomiting respectively in 4, 1, 7 and 5 patients. Progression-free survival and overall survival were respectively 90% and 91.7% at 6 months; 58.3 and 71.3% at 12 months; 31.1 and 71.3% at 18 months., Conclusion: Early postsurgical temozolomide treatment prior to standard adjuvant therapy for poor prognosis glioblastoma patients in our small prospective series presents toxicity and survival similar to those published in the literature for the general population of glioblastoma. These encouraging results should be confirmed by a multicentric study comparing this regiment with the standard treatment., (Copyright © 2018 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: Right ventricular (RV) dysfunction remains the leading cause of early death after cardiac transplantation. Methylprednisolone is used to improve graft quality; however, evidence for that remains empirical. We sought to determine whether methylprednisolone, acting on inflammation and apoptosis, might prevent brain death-induced RV dysfunction., Methods: After randomization to placebo (n = 11) or to methylprednisolone (n = 8; 15 mg/kg), 19 pigs were assigned to a brain-death procedure. The animals underwent hemodynamic evaluation at 1 and 5 hours after Cushing reflex (i.e., hypertension and bradycardia). The animals euthanized, and myocardial tissue was sampled. This was repeated in a control group (n = 8)., Results: At 5 hours after the Cushing reflex, brain death resulted in increased pulmonary artery pressure (27 ± 2 vs 18 ± 1 mm Hg) and in a 30% decreased ratio of end-systolic to pulmonary arterial elastances (Ees/Ea). Cardiac output and right atrial pressure did not change. This was prevented by methylprednisolone. Brain death-induced RV dysfunction was associated with increased RV expression of heme oxygenase-1, interleukin (IL)-6, IL-10, IL-1β, tumor necrosis factor (TNF)-α, IL-1 receptor-like (ST)-2, signal transducer and activator of transcription-3, intercellular adhesion molecules-1 and -2, vascular cell adhesion molecule-1, and neutrophil infiltration, whereas IL-33 expression decreased. RV apoptosis was confirmed by terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling staining. Methylprednisolone pre-treatment prevented RV-arterial uncoupling and decreased RV expression of TNF-α, IL-1 receptor-like-2, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and neutrophil infiltration. RV Ees/Ea was inversely correlated to RV TNF-α and IL-6 expression., Conclusions: Brain death-induced RV dysfunction is associated with RV activation of inflammation and apoptosis and is partly limited by methylprednisolone., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was developed for reliably quantifying hepcidin-25 in human urine and serum. A 95% reference range was established for serum hepcidin-25 levels by standardizing the sampling time between 8:00am and 11:00am in 90 apparently healthy volunteers. The association between hepcidin-25 concentration and other biological parameters was studied using multivariable analysis and the coefficient of renal excretion of hepcidin-25 was calculated. Preanalytical variables were also investigated. The LC-MS/MS method was validated using a recent validation strategy based on accuracy profiles. Good results were obtained in terms of trueness, precision, and linearity in the following dosing ranges: from 0.77 to 200nmol/L for urine and from 0.48 to 100nmol/L for serum. The 95% reference range of serum hepcidin-25 concentration established after excluding known conditions that affect hepcidin-25 expression was 1.5 to 15.2nmol/L. A difference between genders was demonstrated with a median concentration of 5.5 versus 7.2nmol/L for women and men, respectively. Serum hepcidin-25 concentrations were strongly correlated with ferritin and, to a lesser extent, with iron levels. The coefficient of renal excretion ranged from 0.1 to 16.4%. Higher values of hepcidin-25 concentrations were observed on ethylene diamine tetraacetate tubes compared to serum or lithium-heparin devices., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background & Aims: In patients with cirrhosis and refractory ascites the role of beta-blockers in the development of paracentesis-induced circulatory dysfunction (PICD) is unknown. The aim of this study was to investigate the incidence of PICD before and after discontinuation of beta-blockers in patients with cirrhosis and refractory ascites. A self control cross-over study was performed., Methods: Patients with cirrhosis and refractory ascites treated with beta-blockers were selected. Heart rate, arterial pressure, and plasma renin concentrations (PRC) were collected before, immediately after and 1 week after large-volume paracentesis associated with intravenous albumin administration. Beta-blocker therapy was progressively discontinued after complete endoscopic eradication of varices. The clinical and biological evaluation was then repeated. The presence of PICD was defined as an increase in PRC of at least 50% above baseline 1 week after paracentesis., Results: Ten patients were included (nine men, mean age 59.1 ± 10.7 years old). The MELD score was 17.7 ± 4.4 and eight patients were Child-Pugh C. When patients were given beta-blockers, the heart rate did not change immediately after paracentesis while mean arterial pressure significantly decreased; PICD developed in eight patients. After beta-blockers were discontinued, the heart rate significantly increased immediately after paracentesis and mean arterial pressure significantly decreased; PICD only developed in one patient; the difference in the incidence of PICD was significant when these same patients were treated with beta-blockers., Conclusions: The use of beta-blockers may be associated with a high risk of PICD in patients with cirrhosis and refractory ascites., (Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In the Framingham studies, systemic arterial pulse pressure correlated linearly with morbidity and mortality. Right ventricular (RV) systolic dysfunction and pulmonary circulation stiffening result in abnormalities of pulmonary arterial (PA) pulse pressure in PA hypertension (PAH). We investigated the prognostic potential of PA pulse pressure in 67 patients with PAH diagnosed between January 1996 and March 2004 (33 idiopathic PAH, 34 PAH-connective tissue disease). The population was arbitrarily divided into tertiles of PA pulse pressure (= systolic-diastolic PA pressure) and 5-year mortality was assessed using the Kaplan-Meier method. The extent of RV systolic dysfunction and pulmonary circulation stiffening within each tertile was assessed by comparing the mean cardiac index and alpha (a recently described measure of pulmonary circulation distensibility) in each. Independent predictors of mortality were identified by Cox regression. Five-year mortality rates in patients with low, intermediate and high pulse pressures were 40%, 91% and 54%, respectively. Pulse pressure did not independently predict mortality, but cardiac index, 6-min walk test distance and mixed venous oxygen saturation did. Pulse pressure correlated with circulation stiffening (alpha) but did not correlate with cardiac index which tended to be lower in patients with intermediate pulse pressure and high mortality. PA pulse pressure correlated with pulmonary circulation stiffening but did not predict mortality in this study. RV dysfunction provided better prognostic information and probably explains the higher mortality seen in patients with intermediate pulse pressure.

Background: The peripheral chemoreceptors are the dominant reflex mechanism responsible for the rise in ventilation and muscle sympathetic nerve activity (MSNA) in response to hypoxia. Animal studies have suggested that endothelin (ET) plays an important role in chemosensitivity. Moreover, several human clinical conditions in which circulating ET levels are increased are accompanied by enhanced chemoreflex sensitivity. Whether ET plays a role in normal human chemosensitivity is unknown., Methods: We determined whether bosentan, a nonspecific ET receptor antagonist, would decrease chemoreflex sensitivity in 14 healthy subjects. We assessed the effects of bosentan on the response to isocapnic hypoxia, using a randomized, crossover, double-blinded study design., Results: Bosentan increased mean (+/- SEM) plasma ET levels from 1.97 +/- 0.28 to 2.53 +/- 0.23 pg/mL (p = 0.01). Hypoxia increased mean minute ventilation from 6.7 +/- 0.3 to 8+/0.4 L/min (p < 0.01), mean MSNA from 100 to 111 +/- 5% (p < 0.01), mean heart rate from 67 +/- 3 to 86 +/- 3 beats/min (p < 0.01), and mean systolic BP from 116 +/- 3 to 122 +/- 3 mm Hg (p < 0.01). However, none of these responses differed between therapy with bosentan and therapy with placebo (p = 0.26). Bosentan did not affect the mean MSNA responses to the apneas, during normoxia (change from baseline: placebo, 259 +/- 58%; bosentan, 201 +/- 28%; p = 0.17) or during hypoxia (change from baseline: placebo, 469 +/- 139%; bosentan, 329 +/- 46%; p = 0.24). The durations of the voluntary end-expiratory apneas in normoxia and hypoxia, and the subsequent reductions in oxygen saturation, were also similar with therapy using bosentan and placebo (p = 0.42)., Conclusion: In healthy men, ET does not play an important role in peripheral chemoreceptor activation by acute hypoxia.

Study Objectives: To investigate the current practice of tracheostomy in French ICUs, focusing on the frequency, timing, indications, and techniques., Design: A retrospective study., Setting: A questionnaire was sent to all ICUs included in the national registry of the Societe de Reanimation de Langue Francaise., Patients: All ICU patients receiving mechanical ventilation (MV) during the year preceding the survey (excluding noninvasive ventilation) were covered by the questionnaire., Intervention: None., Measurements and Results: Of the 708 ICUs invited to participate, 152 (21.5%) answered the questionnaire. Overall, 35,322 patients (median, 212 patients per unit; interquartile range [IQR], 148 to 329 patients) had received MV, including one fourth of patients for > 7 days. A median of 7.2% of patients (IQR, 2.9 to 11.1%) had undergone a tracheostomy. The most frequently reported indications for tracheostomy were prolonged MV (95%, after a median of 20 days) and failure of extubation (48%). An indication for "early" tracheostomy (ie, < 3 weeks) was considered in 68% of the ICUs, after a median time of 7 days. Physicians thought that performing tracheostomy would facilitate weaning from MV and early oral nutrition, and would improve overall patient comfort. The main disadvantages listed were tracheal complications, the aggressiveness of the procedure, and the risk of infection. Surgical techniques largely remained preferred compared to percutaneous techniques., Conclusions: There is much heterogeneity in the reported practices of tracheostomy in French ICUs. Three fourths of physicians considered that a randomized study comparing prolonged translaryngeal intubation and early tracheostomy in patients expected to receive prolonged MV would be necessary to clarify those issues.

Study Objectives: To determine possible differences in morbidity and mortality between early and late onset of septic shock in ICU patients., Design: Systematic data collection., Setting: Thirty-one-bed, mixed, medicosurgical ICU in a university hospital., Patients: All 65 patients who acquired septic shock after admission to the ICU between February 1999 and April 2000., Interventions: None., Measurements and Results: Forty-one of the 65 patients presented with septic shock within 24 h of admission to the ICU (early septic shock [ESS]); the other 21 patients acquired septic shock > 24 h after ICU admission (late septic shock [LSS]). Eleven patients had a second episode (7 patients in the ESS group, and 4 patients in the LSS group), and 1 patient in the LSS group had a third episode of septic shock. Patients with ESS had higher APACHE (acute physiology and chronic health evaluation) II (mean +/- SD, 26 +/- 6 vs 20 +/- 6; p = 0.002) and sequential organ failure assessment (SOFA) scores (11 +/- 3 vs 7 +/- 3, p < 0.001) on ICU admission, and a higher blood lactate concentration at the onset of shock (median 3.70 mEq/L; interquartile range, 2.6 to 6.6 mEq/L; vs median, 2.50 mEq/L [interquartile range, 1.8 to 4.0 mEq/L], p = 0.03) than patients with LSS. However, the duration of septic shock (median, 42 h [interquartile range, 21 to 97 h] vs median, 93 h [interquartile range, 32 to 241 h], p = 0.058) and the length of ICU stay after the onset of septic shock (median, 75 h; [interquartile range, 38 to 203 h] vs median, 321 h [interquartile range, 96 to 438 h], p = 0.018), was shorter in patients with ESS than patients with LSS. The ICU mortality rate was 63% (26 patients) in the ESS group, and 88% (21 patients) in the LSS group (p = 0.071). At the onset of the first episode of shock, patients with ESS had higher SOFA scores (11 +/- 3 vs 9 +/- 3, p = 0.045), lower pH (7.24 +/- 0.15 vs 7.33 +/- 0.12, p = 0.01), and were treated with higher doses of dopamine (median, 20 microg/kg/min [interquartile range, 14 to 20 microg/kg/min] vs median, 12 microg/kg/min [interquartile range, 8 to 20 microg/kg/min], p = 0.028) than patients with LSS., Conclusions: Septic shock is more severe when of early onset, as reflected by more severe organ dysfunction, greater lactic acidosis, and higher vasopressor requirements, yet the outcome is better, as reflected by a shorter duration of the shock episode, shorter ICU stay, and slightly lower mortality rates. These differences may influence clinical trials of therapeutic agents for sepsis, and should be taken into account when analyzing the results.