Weaning from mechanical ventilation in neurocritical care.

In the intensive care unit (ICU), weaning from mechanical ventilation follows a step-by-step process that has been well established in the general ICU population. However, little data is available in brain injury patients, who are often intubated to protect airways and prevent central hypoventilation. In this narrative review, we describe the general principles of weaning and how these principles can be adapted to brain injury patients. We focus on three major issues regarding weaning from mechanic ventilation in brain injury patients: (1) sedation protocol, (2) weaning and extubation protocol and criteria, (3) criteria, timing and technique for tracheostomy.

Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome. Objective: To assess the safety of inulin and sinistrin use in France. Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin. Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign. Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.

Management of liver failure in general intensive care unit.

OBJECTIVE: To produce French guidelines on Management of Liver failure in general Intensive Care Unit (ICU). DESIGN: A consensus committee of 23 experts from the French Society of Anesthesiology and Critical Care Medicine (Société française d'anesthésie et de réanimation, SFAR) and the French Association for the Study of the Liver (Association française pour l'étude du foie, AFEF) was convened. A formal conflict-of-interest (COI) policy was developed at the start of the process and enforced throughout. The entire guideline process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide their assessment of the quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. Some recommendations were ungraded. METHODS: Two fields were defined: acute liver failure (ALF) and cirrhotic patients in general ICU. The panel focused on three questions with respect to ALF: (1) Which etiological examinations should be performed to reduce morbidity and mortality? (2) Which specific treatments should be initiated rapidly to reduce morbidity and mortality? (3) Which symptomatic treatment should be initiated rapidly to reduce morbidity and mortality? Seven questions concerning cirrhotic patients were addressed: (1) Which criteria should be used to guide ICU admission of cirrhotic patients in order to improve their prognosis? (2) Which specific management of kidney injury should be implemented to reduce morbidity and mortality in cirrhotic ICU patients? (3) Which specific measures to manage sepsis in order to reduce morbidity and mortality in cirrhotic ICU patients? (4) In which circumstances, human serum albumin should be administered to reduce morbidity and mortality in cirrhotic ICU patients? (5) How should digestive haemorrhage be treated in order to reduce morbidity and mortality in cirrhotic ICU patients? (6) How should haemostasis be managed in order to reduce morbidity and mortality in cirrhotic ICU patients? And (7) When should advice be obtained from an expert centre in order to reduce morbidity and mortality in cirrhotic ICU patients? Population, intervention, comparison and outcome (PICO) issues were reviewed and updated as required, and evidence profiles were generated. An analysis of the literature and recommendations was then performed in accordance with the GRADE® methodology. RESULTS: The SFAR/AFEF Guidelines panel produced 18 statements on liver failure in general ICU. After two rounds of debate and various amendments, a strong agreement was reached on 100% of the recommendations: six had a high level of evidence (Grade 1 ±), seven had a low level of evidence (Grade 2 ±) and six were expert judgments. Finally, no recommendation was provided with respect to one question. CONCLUSIONS: Substantial agreement exists among experts regarding numerous strong recommendations on the optimum care of patients with liver failure in general ICU.

Original Study: Transjugular Intrahepatic Portosystemic Shunt as a Bridge to Abdominal Surgery in Cirrhotic Patients.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) has been suggested to reduce portal hypertension-associated complications in cirrhotic patients undergoing abdominal surgery. The aim of this study was to compare postoperative outcome in cirrhotic patients with and without specific preoperative TIPS placement, following elective extrahepatic abdominal surgery. METHODS: Patients were retrospectively included from 2005 to 2016 in four centers. Patients who underwent preoperative TIPS (n = 66) were compared to cirrhotic control patients without TIPS (n = 68). Postoperative outcome was analyzed using propensity score with inverse probability of treatment weighting analysis. RESULTS: Overall, colorectal surgery accounted for 54% of all surgical procedure. TIPS patients had a higher initial Child-Pugh score (6[5-12] vs. 6[5-9], p = 0.043) and received more beta-blockers (65% vs. 22%, p < 0.001). In TIPS group, 56 (85%) patients managed to undergo planned surgery. Preoperative TIPS was associated with less postoperative ascites (hazard ratio = 0.330 [0.140-0.780]). Severe postoperative complications (Clavien-Dindo > 2) and 90-day mortality were similar between TIPS and no-TIPS groups (18% vs. 23%, p = 0.392, and 7.5% vs. 7.8%, p = 0.644, respectively). CONCLUSIONS: Preoperative TIPS placement yielded an 85% operability rate with satisfying postoperative outcomes. No significant differences were found between TIPS and no-TIPS groups in terms of severe postoperative complications and mortality, although TIPS patients probably had worse initial portal hypertension.

Root cone angle is enlarged in docs1 LRR-RLK mutants in rice.

BACKGROUND: The DEFECTIVE IN OUTER CELL LAYER SPECIFICATION 1 (DOCS1) gene belongs to the Leucine-Rich Repeat Receptor-Like Kinase (LRR-RLK) subfamily. It has been discovered few years ago in Oryza sativa (rice) in a screen to isolate mutants with defects in sensitivity to aluminum. The c68 (docs1-1) mutant possessed a nonsense mutation in the C-terminal part of the DOCS1 kinase domain. FINDINGS: We have generated a new loss-of-function mutation in the DOCS1 gene (docs1-2) using the CRISPR-Cas9 technology. This new loss-of-function mutant and docs1-1 present similar phenotypes suggesting the original docs1-1 was a null allele. Besides the aluminum sensitivity phenotype, both docs1 mutants shared also several root phenotypes described previously: less root hairs and mixed identities of the outer cell layers. Moreover, our new results suggest that DOCS1 could also play a role in root cap development. We hypothesized these docs1 root phenotypes may affect gravity responses. As expected, in seedlings, the early gravitropic response was delayed. Furthermore, at adult stage, the root gravitropic set angle of docs1 mutants was also affected since docs1 mutant plants displayed larger root cone angles. CONCLUSIONS: All these observations add new insights into the DOCS1 gene function in gravitropic responses at several stages of plant development.

Piperazine derivatives as iron chelators: a potential application in neurobiology.

Polysubstituted piperazine derivatives, designed as new iron chelators, were synthesized and fully characterized by nuclear magnetic resonance and mass spectroscopy. Their potential to prevent iron-induced neurotoxicity was assessed using a cellular model of Parkinson disease. We demonstrated their ability to provide sustained neuroprotection to dopaminergic neurons that are vulnerable in this pathology. The iron chelating properties of the new compounds were determined by spectrophotometric titration illustrating that high affinity for iron is not associated with important neuroprotective effects.

Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E.

Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage­Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.

Successive bioanode regenerations to maintain efficient current production from biowaste.

The long-term operation of efficient bioanodes supplied with waste-derived organics is a key challenge for using bioelectrochemical systems as a waste valorization technology. Here, we describe a simple procedure that allowed maintaining highly efficient bioanodes supplied with biowaste. Current densities up to 14.8 A/m(2) were obtained with more than 40% of the electrons introduced as biowaste being recovered in the electrical circuit. Three fed-batch reactors were started at different biowaste loading rates. A decline of coulombic efficiencies between 22 and 31% was recorded depending on the reactor over the first 3 weeks of operation. A renewal procedure of the anode was thereafter implemented, which led to a recovery of initial performances. The second and the third renewal, allowed maintaining stable high level performances with coulombic efficiency of approximately 40% over at least 3 weeks. Electroactive biofilm dynamics were monitored using 16S rRNA-gene amplicon sequencing. Retrieved sequences were dominated by Geobacter sulfurreducens-related reads (37% of total sequences), which proportion however varied along the experiment. Interestingly, sequences affiliated to various Bacteroidetes groups were also abundant, suggesting an adaptation of the anodic biofilm to the degradation of biowaste through metabolic interactions between microbial community members.

Prevalence, incidence and risk factors for donor-specific anti-HLA antibodies in maintenance liver transplant patients.

Although large retrospective studies have identified the presence of donor-specific antibodies (DSAs) to be a risk factor for rejection and impaired survival after liver transplantation, the long-term predicted pathogenic potential of individual DSAs after liver transplantation remains unclear. We investigated the incidence, prevalence and consequences of DSAs in maintenance liver transplant (LT) recipients. Two hundred sixty-seven LT recipients, who had undergone transplantation at least 6 months previously and had been screened for DSAs at least twice using single-antigen bead technology, were included and tested annually for the presence of DSAs. At a median of 51 months (min-max: 6-220) after an LT, 13% of patients had DSAs. At a median of 36.5 months (min-max: 2-45) after the first screening, 9% of patients have developed de novo DSAs. The sole predictive factor for the emergence of de novo DSAs was retransplantation (OR 3.75; 95% CI 1.28-11.05, p = 0.025). Five out of 21 patients with de novo DSAs (23.8%) developed an antibody-mediated rejection. Fibrosis score was higher among patients with DSAs. In conclusion, monitoring for the development of DSAs in maintenance LT patients is useful in case of graft dysfunction and to identify patients with a high risk of developing liver fibrosis.

Hepatitis B screening: who to target? A French sexually transmitted infection clinic experience.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is a major public health burden in France and worldwide. Routine screening for hepatitis B is not currently recommended in France. Medical experts and public health agencies opinions can differ concerning targeting criteria. Our study aims at developing a risk assessment strategy for identifying possible hepatitis B cases among the patients consulting in a French Sexually Transmitted Infection (STI) clinic. METHODS: 6194 asymptomatic patients requesting an STI screening were also screened for hepatitis B infection. The association between hepatitis B surface antigen (HBsAg) positivity and/or total hepatitis B core antibody (anti-HBc) positivity and self-reported risk factors for hepatitis were analysed. RESULTS: Only male gender, lack of employment, and birth, in medium or high endemic country, were independently associated with HBsAg positivity in multivariate analysis. Sexual behaviour or self-reported vaccination status is therefore not necessary to target high-risk populations. These three simple criteria could save 25% of unnecessary tests and 6-16% undiagnosed hepatitis B compared to usual targeting criteria. CONCLUSIONS: To detect HBsAg carriers, only three simple targeting criteria, without taking into account the self-reported vaccination status or sexual behaviour, could improve screening efficiency and save unnecessary testing.

[Transjugular intrahepatic portosystemic shunt before hepatic surgery in a patient with cirrhosis and portal hypertension: case report]. / Dérivation portocave intrahépatique transjugulaire avant chirurgie hépatique en cas de cirrhose compliquée d'hypertension portale.

Major abdominal surgery may be contraindicated in patients with cirrhosis because of the high risk of intraoperative bleeding and postoperative decompensation. Careful preparation of these patients is essential, aimed especially at reducing portal hypertension. We report the case of a patient with cirrhosis complicated by hepatocellular carcinoma, whose portal hypertension manifested almost exclusively by reanastomosis from the umbilical vein. A transjugular intrahepatic portosystemic shunt (TIPS) was placed before surgery to prepare the patient for hepatic resection. In addition to the singularity of the presentation of portal hypertension, this case prompts us to consider neoadjuvant TIPS as a means of preparing these at-risk patients for major abdominal surgery.

Adhesion and fitness in the bean phyllosphere and transmission to seed of Xanthomonas fuscans subsp. fuscans.

Deciphering the mechanisms enabling plant-pathogenic bacteria to disperse, colonize, and survive on their hosts provides the necessary basis to set up new control methods. We evaluated the role of bacterial attachment and biofilm formation in host colonization processes for Xanthomonas fuscans subsp. fuscans on its host. This bacterium is responsible for the common bacterial blight of bean (Phaseolus vulgaris), a seedborne disease. The five adhesin genes (pilA, fhab, xadA1, xadA2, and yapH) identified in X. fuscans subsp. fuscans CFBP4834-R strain were mutated. All mutants were altered in their abilities to adhere to polypropylene or seed. PilA was involved in adhesion and transmission to seed, and mutation of pilA led to lower pathogenicity on bean. YapH was required for adhesion to seed, leaves, and abiotic surfaces but not for in planta transmission to seed or aggressiveness on leaves. Transmission to seed through floral structures did not require any of the known adhesins. Conversely, all mutants tested, except in yapH, were altered in their vascular transmission to seed. In conclusion, we showed that adhesins are implicated in the various processes leading to host phyllosphere colonization and transmission to seed by plant-pathogenic bacteria.

Impact of nitrate-enhanced leachate recirculation on gaseous releases from a landfill bioreactor cell.

This study evaluates the impact of nitrate injection on a full scale landfill bioreactor through the monitoring of gaseous releases and particularly N(2)O emissions. During several weeks, we monitored gas concentrations in the landfill gas collection system as well as surface gas releases with a series of seven static chambers. These devices were directly connected to a gas chromatograph coupled to a flame ionisation detector and an electron capture detector (GC-FID/ECD) placed directly on the field. Measurements were performed before, during and after recirculation of raw leachate and nitrate-enhanced leachate. Raw leachate recirculation did not have a significant effect on the biogas concentrations (CO(2), CH(4) and N(2)O) in the gas extraction network. However, nitrate-enhanced leachate recirculation induced a marked increase of the N(2)O concentrations in the gas collected from the recirculation trench (100-fold increase from 0.2 ppm to 23 ppm). In the common gas collection system however, this N(2)O increase was no more detectable because of dilution by gas coming from other cells or ambient air intrusion. Surface releases through the temporary cover were characterized by a large spatial and temporal variability. One automated chamber gave limited standard errors over each experimental period for N(2)O releases: 8.1 +/- 0.16 mg m(-2) d(-1) (n = 384), 4.2 +/- 0.14 mg m(-2) d(-1) (n = 132) and 1.9 +/- 0.10 mg m(-2) d(-1) (n = 49), during, after raw leachate and nitrate-enhanced leachate recirculation, respectively. No clear correlation between N(2)O gaseous surface releases and recirculation events were evidenced. Estimated N(2)O fluxes remained in the lower range of what is reported in the literature for landfill covers, even after nitrate injection.

Management of failures of first line treatments.

Up to 70% of the patients treated to prevent rebleeding will experience a bleeding episode within 2 years. The response should be adapted to the delay after the index bleed, the source and the severity of the haemorrhage, the underlying liver disease and the initial treatment to prevent rebleeding. Bleeding can be caused by endoscopic techniques themselves, which should incitate to complete obliteration rather than to switch to another therapy. Failure of drug therapy can be secondary to ineffectiveness, to a lack of compliance, or to an insufficient dosage. The two latter conditions may be corrected. Whenever a patient rebleeds in spite of optimal treatment, liver transplantation should be considered. When such a procedure is contra-indicated and in patients on the waiting list, a Transjugular intra-hepatic porto-systemic shunt (TIPS) should be performed.

Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease.

BACKGROUND: Hepatic venous pressure gradient (HVPG) is a prognostic marker in patients with cirrhosis. Transient elastography measures liver stiffness (LS). AIM: To assess the correlation between LS and HVPG and to investigate the performance of transient elastography for the diagnosis of significant portal hypertension (PHT). METHODS: Liver stiffness was measured by Fibroscan in 150 consecutive patients who underwent a liver biopsy with haemodynamic measurements. Usual clinical and biological data were collected. Significant PHT was defined as a HVPG > or = 10 mmHg. RESULTS: Hepatic venous pressure gradient was found to be > or = 10 mmHg in 76 patients. Cirrhosis was diagnosed in 89 patients. HVPG was found to be correlated with: LS (rho = 0.858; P < 0.001) and inversely correlated with prothrombin index (rho = -0.718; P < 0.001). Regarding significant PHT, AUROC for LS and prothrombin index were 0.945 [0.904-0.987] and 0.892 [0.837-0.947] respectively. The cut-off value of 21 kPa accurately predicted significant PHT in 92% of the 144 patients for whom LS was successful. CONCLUSION: Liver stiffness measurement is correlated with HVPG and transient elastography identifies patients with significant PHT.