Ischemic injury of the upper gastrointestinal tract after out-of-hospital cardiac arrest: a prospective, multicenter study.

BACKGROUND: The consequences of cardiac arrest (CA) on the gastro-intestinal tract are poorly understood. We measured the incidence of ischemic injury in the upper gastro-intestinal tract after Out-of-hospital CA (OHCA) and determined the risk factors for and consequences of gastrointestinal ischemic injury according to its severity. METHODS: Prospective, non-controlled, multicenter study in nine ICUs in France and Belgium conducted from November 1, 2014 to November 30, 2018. Included patients underwent an esophago-gastro-duodenoscopy 2 to 4 d after OHCA if still intubated and the presence of ischemic lesions of the upper gastro-intestinal tract was determined by a gastroenterologist. Lesions were a priori defined as severe if there was ulceration or necrosis and moderate if there was mucosal edema or erythema. We compared clinical and cardiac arrest characteristics of three groups of patients (no, moderate, and severe lesions) and identified variables associated with gastrointestinal ischemic injury using multivariate regression analysis. We also compared the outcomes (organ failure during ICU stay and neurological status at hospital discharge) of the three groups of patients. RESULTS: Among the 214 patients included in the analysis, 121 (57%, 95% CI 50-63%) had an upper gastrointestinal ischemic lesion, most frequently on the fundus. Ischemic lesions were severe in 55/121 (45%) patients. In multivariate regression, higher adrenaline dose during cardiopulmonary resuscitation (OR 1.25 per mg (1.08-1.46)) was independently associated with increased odds of severe upper gastrointestinal ischemic lesions; previous proton pump inhibitor use (OR 0.40 (0.14-1.00)) and serum bicarbonate on day 1 (OR 0.89 (0.81-0.97)) were associated with lower odds of ischemic lesions. Patients with severe lesions had a higher SOFA score during the ICU stay and worse neurological outcome at hospital discharge. CONCLUSIONS: More than half of the patients successfully resuscitated from OHCA had upper gastrointestinal tract ischemic injury. Presence of ischemic lesions was independently associated with the amount of adrenaline used during resuscitation. Patients with severe lesions had higher organ failure scores during the ICU stay and a worse prognosis. Clinical Trial Registration NCT02349074 .

Reduced acquisition time for thallium myocardial perfusion imaging with large field cadmium-zinc-telluride SPECT/CT cameras: An equivalence study.

BACKGROUND: Cadmium-zinc-telluride (CZT) SPECT/CT cameras with large field of view offer a higher sensitivity than conventional Anger cameras. This prospective study aimed to determine the equivalence between a conventional protocol and a reduced acquisition time protocol for 201-Thallium myocardial perfusion imaging (MPI) using a whole-body CZT SPECT camera. METHODS AND RESULTS: Stress MPI was obtained for 103 consecutive patients on a DISCOVERY-CZT camera. Images were anonymized and post-processed to simulate a 25% (D75 dataset) and 50% (D50 dataset) decrease in total recorded counts. Concerning the number of segments displaying a tracer uptake < 70% of maximum intensity per patient, equivalence was demonstrated for both count-reduced datasets with a good inter-observer agreement (between 0.90 and 0.88). When comparing the full-vs-D75 datasets and full-vs-D50 datasets, mean difference was 0.06 segment (CI95: [- 0.15;0.27], P < 0.001) and 0.518 segment (CI95: [0.28;0.76], P < 0.001) respectively. Inter-observer agreement was also moderate to good concerning the number of pathological segments (between 0.6 and 0.7) and excellent for functional parameters. CONCLUSION: Whole-body CZT SPECT/CT cameras allow to reduce 201-Thallium MPI injected activity or acquisition time by 50% with an equivalence in the number of segments displaying a tracer uptake < 70% of maximum intensity and with a good inter-observer agreement.

Enzymatic activity monitoring through dynamic nuclear polarization in Earth magnetic field.

Cost-effective and portable MRI systems operating at Earth-field would be helpful in poorly accessible areas or in developing nations. Furthermore Earth-field MRI can provide new contrasts opening the way to the observation of pathologies at the biochemical level. However low-field MRI suffers from a dramatic lack in detection sensitivity even worsened for molecular imaging purposes where biochemical specificity requires detection of dilute compounds. In a preliminary spectroscopic approach, it is proposed here to detect protease-driven hydrolysis of a nitroxide probe thanks to electron-nucleus Overhauser enhancement in a home-made double resonance system in Earth-field. The combination of the Overhauser effect and the specific enzymatic modification of the probe provides a smart contrast reporting the enzymatic activity. The nitroxide probe is a six-line nitroxide which lines are shifted according to its substrate/product state, which requires quantum mechanical calculations to predict EPR line frequencies and Overhauser enhancements at Earth field. The NMR system is equipped with a 13-mT prepolarization coil, a 153-MHz EPR coil and a 2-kHz NMR coil. Either prepolarized NMR or DNP-NMR without prepolarization provide NMR spectra within 3 min. The frequency dependence of Overhauser enhancement was in agreement with theoretical calculations. Protease-mediated catalysis of the nitroxide probe could only be measured through the Overhauser effect with 5 min time resolution. Future developments shall open the way for the design of new low-field DNP-MRI systems.

Probing the dynamic properties of two sites simultaneously in a protein-protein interaction process: a SDSL-EPR study.

During molecular processes, protein flexibility is a fundamental property allowing protein-protein interaction. Following structural changes during these interactions is then of crucial interest. Site-Directed Spin Labeling (SDSL) combined to EPR spectroscopy is a powerful technique to follow structural modifications within proteins and during protein-protein interactions. Usual nitroxide labels target cysteine residues and afford a 3-line spectrum, whose shape is informative of the structural environment of the label. However, it is not possible to probe two regions of a protein or two partner proteins at the same time because of the overlapping of EPR signatures. Previously, we reported the design and the characterization of a spin label based on a ß-phosphorylated (PP) nitroxide yielding a 6-line spectrum. Here, we report the use of two labels with different EPR signatures, namely maleimido-proxyl (P) and PP, to follow structural changes during a protein-protein interaction process in one single experiment. As a model system, we chose a disordered protein that undergoes an induced α-helical folding upon binding to its partner. We show that the EPR spectrum of a mixture of labeled interacting proteins can be analyzed in terms of structural changes during the interaction. This study represents an important step forward in the extension of the panoply of SDSL-EPR approaches.

Feasibility and safety of ultra-low tidal volume ventilation without extracorporeal circulation in moderately severe and severe ARDS patients.

PURPOSE: Mechanical ventilation with ultra-low tidal volume (VT) during ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury, with the main drawback of worsening respiratory acidosis. We hypothesized that VT could be reduced down to 4 ml/kg, with clinically significant decrease in driving pressure, without the need for extracorporeal CO2 removal, while maintaining pH > 7.20. METHODS: We conducted a non-experimental before-and-after multicenter study on 35 ARDS patients with PaO2/FiO2 ≤ 150 mmHg, within 24 h of ARDS diagnosis. After inclusion, VT was reduced to 4 ml/kg and further adjusted to maintain pH ≥ 7.20, respiratory rate was increased up to 40 min-1 and PEEP was set using a PEEP-FiO2 table. The primary judgment criterion was driving pressure on day 2 of the study, as compared to inclusion. RESULTS: From inclusion to day 2, driving pressure decreased significantly from 12 [9-15]  to 8 [6-11] cmH2O, while VT decreased from 6.0 [5.9-6.1] to 4.1 [4.0-4.7] ml/kg. On day 2, VT was below 4.2 ml/kg in 65% [CI95% 48%-79%], and below 5.25 ml/kg in 88% [CI95% 74%-95%] of the patients. 2 patients (6%) developed acute cor pulmonale after inclusion. Eleven patients (32%) developed transient severe acidosis with pH < 7.15. Fourteen patients (41%) died before day 90. CONCLUSION: Ultra-low tidal volume ventilation may be applied in approximately 2/3 of moderately severe-to-severe ARDS patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients.

Lactobacillus acidophilus versus placebo in the symptomatic treatment of irritable bowel syndrome: the LAPIBSS randomized trial.

Irritable bowel syndrome is a chronic functional gastrointestinal disorder characterized by abdominal pain/discomfort and altered bowel habits. The use of Lactobacilli as probiotics during irritable bowel syndrome is based on their interesting mechanisms of action and their excellent safety profile but little is known about their clinical efficacy due to the lack of adequately designed clinical trials. The current clinical trial protocol aims to determine the effects of a mixture of Lactobacillus acidophilus NCFM and LAFTI L10 as probiotics to improve irritable bowel syndrome symptoms (LAPIBSS). Eighty patients with a positive diagnosis of irritable bowel syndrome according to Rome III criteria were recruited to a multicentre, double-blinded, in parallel groups, placebo-controlled randomized trial. Patients were provided with a daily dose of two capsules with two strains of Lactobacilli (5x109cfu/capsule) or placebo for 8 weeks on a 1:1 ratio. The primary outcome is to obtain scores of abdominal pain/discomfort assessed with a 100-mm visual analogue scale. The secondary outcome is to obtain scores of bloating, flatus and rumbling tested with a 100-mm visual analogue scale, composite score, stool frequency and stool consistency/appearance assessed with the Bristol Stool Form scale. According to the hypothesis that abdominal pain is mainly the result of a visceral hypersensitivity, the current study protocol aims to provide high quality proof of concept data to elucidate the efficacy of a consumption of a mixture of Lactobacillus acidophilus probiotic strains after 8 weeks, for decreasing abdominal pain. Ethical approval was given by ethics committee French Consultative Committee for the Protection of Individuals in Biomedical Research of the South West (Number CPP08-014a) and ANSM (French National Agency for Medicines and Health Products Safety - Number B80623-40). The findings from LAPBISS will be disseminated through peer-reviewed publications and at scientific conferences. TRIAL REGISTRATION: EudraCT N°2008-A00844-51.

Tibial tubercle torsion, a new factor of patellar instability.

INTRODUCTION: External torsion of the anterior tibial tubercle (TT), defined as external rotation around a craniocaudal axis with respect to the posterior femoral condylar plane, may induce patellar instability. To our knowledge no studies have focused on this parameter. The present study aimed to perform an MRI analysis of TT torsion. The study hypothesis was that TT torsion correlates with patellar instability and with 3 of its components: tibial tubercle-trochlear groove (TT-TG) distance, axial engagement index of the patella (AEI), and patellar tilt. MATERIAL AND METHODS: Four observers performed MRI measurements for 2 groups: 37 patellar instability patients (PI group) with history of at least 2 patellar dislocations, and 50 control patients with meniscal lesion but free from patellofemoral pathology. All measurements were taken from 2 axial slices with the posterior condylar plane as reference. RESULTS: The intra-class correlation coefficient (ICC) was 0.88. TT torsion correlated with patellar instability, with a mean 5.8̊ in controls and 17.9̊ in the PI group (P<0.001). There were also excellent correlations between TT torsion and TT-TG distance, patellar tilt and patellar lateralization (measured by AEI), with correlation coefficients greater than 0.85. DISCUSSION: TT torsion is a reproducible measurement, with excellent ICC. It is significantly correlated with patellar instability, with a discrimination threshold of 11.5̊, and correlations with all 3 components of instability. These statistical correlations enable TT torsion to be added to the list of patellar instability factors. Further studies should determine its biomechanical role and assess the contribution of associating TT derotation to medialization or distalization procedures. LEVEL OF EVIDENCE: III; case-control study.

Systematic review with meta-analysis: direct comparisons of biomarkers for the diagnosis of fibrosis in chronic hepatitis C and B.

BACKGROUND: Blood tests and transient elastography (TE), proposed as alternatives to biopsy for identifying advanced fibrosis (METAVIR-stage-F2 or greater) or cirrhosis, have never been compared using an intention to diagnose approach, with direct comparisons only, and Bayesian approach. AIM: To permit more appropriate comparisons. METHODS: From an overview of articles (2002-2014), we selected studies that directly compared the diagnostic accuracy of FibroTest, aspartate aminotransferase-platelet ratio index (APRI), FIB4 or TE, with biopsy as a reference, in patients with chronic hepatitis C (CHC) or B (CHB). Investigators abstracted and checked study details and quality by using pre-defined criteria. Bayesian method in intention to diagnose was the primary outcome. RESULTS: Of 1321 articles identified, 71 studies including 77 groups according to aetiology (All-CB) were eligible: 37 Only-C, 28 Only-B and 12 Mixed-C-B. There were 185 direct comparisons between the area under the ROC curves (AUROCs), 99 for the diagnosis of advanced fibrosis and 86 for cirrhosis. In All-CB, Bayesian analyses revealed significant AUROCs differences in identifying advanced fibrosis in favour of FibroTest vs. TE [credibility interval: 0.06(0.02-0.09)], FibroTest vs. APRI [0.05 (0.03-0.07)] and for identifying cirrhosis TE vs. APRI [0.07 (0.02-0.13)] and FIB4 vs. APRI [0.04(0.02-0.05)]. No differences were observed between TE and FibroTest, for identifying cirrhosis in All-CB, and in sub-groups (Only-C, Only-B, Mixed-CB) for both cirrhosis and fibrosis. CONCLUSIONS: In CHC and CHB, APRI had lower performances than FIB-4, TE and FibroTest. TE had lower performance than FibroTest for identifying advanced fibrosis in All-CB, without significant difference for identifying cirrhosis in all groups.

[Severe poisonings in intensive care unit: study of announced substances in 2011]. / Intoxications graves en réanimation : étude des substances annoncées en 2011.

INTRODUCTION: To treat poisonings, physicians must rapidly make a diagnosis. As of today, exhaustive data on most frequently reported toxics are not available in France. MATERIALS AND METHODS: This was a retrospective study of announced substances at patients' admissions in intensive care unit for poisoning in 2011 at Lariboisière hospital. Announced substances were collected from anamnesis reported in patient medical records. Verbatims were harmonized and substances classified in medicinal products and three categories of non-medicinal products (recreational/addictive drugs, others, unknown nature). RESULTS: Three hundred and fifteen patients were included, with 891 announced specified substances corresponding to 198 different verbatims. Most of them (83%) are medicinal products (mainly nervous and cardiovascular system molecules). There were 13% of recreational/addictive substances, 3% of other non-medicinal substances. Of the occurrences, 1.5% represent unknown substances. DISCUSSION: These substances supposedly used in poisoning should be included in toxicology learning programs. Their dosage should be possibly performed in routine by toxicology laboratories. CONCLUSION: An ongoing study in a prospective and retrospective manner will become an observatory of the substances involved in poisoning.

Comparison of two versions of the Vigileo-FloTrac system (1.03 and 1.07) for stroke volume estimation: a multicentre, blinded comparison with oesophageal Doppler measurements.

BACKGROUND: Our aim was to evaluate the validity of stroke volume measurements obtained using the Vigileo-FloTrac system in comparison with those obtained using oesophageal Doppler considered as a reference. METHODS: Prospective, multicentre study (four university hospitals), in which investigators were blinded to stroke volume values acquired simultaneously with the other technique. Two different versions of the Vigileo software (1.03 and 1.07) were studied and compared over two consecutive periods of time. Forty critically ill patients (three ICUs) and 20 high-risk surgical patients (one operating theatre) were studied over a 6-month period. RESULTS: Two hundred and forty paired stroke volume values obtained using the second version of the Vigileo (1.07) yielded better correlation and agreement (R=0.48, P<0.001; bias=4 ml, limits of agreement: +/- 41 ml) than the 207 paired values obtained using version 1.03 (R=0.12, P=0.1; bias=1 ml, limits of agreement: +/- 75 ml). However, even with the second version, the percentage error in stroke volume measurement was 58%, a value still above the range considered clinically acceptable (30%). CONCLUSIONS: The precision of stroke volume estimation using Vigileo-FloTrac has improved with the second version of the software (1.07), but remains insufficient to allow the replacement of the reference technique in the population studied.

Factors influencing the C-O bond homolysis of alkoxyamines: effects of H-bonding and polar substituents.

The synthesis of various new trialkylhydroxylamines is described. The rate constant of the C-O bond cleavage of these new alkoxyamines has been measured. For example, C-O bond homolysis rates in a series of para-substituted TEMPO-styryl compounds TEMPO-CH(CH3)C6H5X 1a (p-MeO), 1b (p-Me), 1d (p-H), 1e (p-Br), and 1f (p-MeO2C) are presented. Furthermore, rate constants for the C-O bond cleavage of alpha-heteroaryl-substituted secondary alkoxyamines are discussed. A correlation by which the rate constant for the C-O bond cleavage of TEMPO-derived alkoxyamines can be predicted from the C-H BDEs of the corresponding alkanes is presented. Solvent effects as well as the effect of camphorsulfonic acid on the rate of the C-O bond homolysis are discussed. Finally, EPR and kinetic evidence show that alkoxyamines derived from nitroxides which are capable of intramolecular H-bonding undergo C-O bond cleavage faster than the corresponding non-H-bond-forming analogues.