Efficiency and safety of total plasma exchange in critically ill cirrhotic patients with acute on chronic liver failure: A pilot study.

BACKGROUND AND AIMS: Treatment of patients with acute on chronic liver failure (ACLF) admitted to the ICU is very limited. The aim of this pilot study was to evaluate the efficiency on liver function and safety of therapeutic plasma exchange (TPE) in critically ill cirrhotic patients admitted with ACLF in a liver ICU. METHODS: This is a prospective cohort of patients with ACLF grade > 2 treated by TPE admitted to the ICU that was matched to a control group. TPE was performed using a plasma filter (TPE2000, BAXTER®) on a CRRT machine (Prismaflex®, Baxter®). Ratio and type of fluid replacement were 50 % with 5 % albumin solution followed by 50 % with fresh frozen plasma. RESULTS: Seven patients with a mean age of 50.6 ± 7.8 years (all males) and 14 controls matched to age, sex, etiology and cause of decompensation were recruited. At ICU admission, mean MELD score was 39.1 ± 2.7, mean SOFA score was 11.6 ± 5.2 and mean CLIF SOFA score was 12.9 ± 2.6. The grade of ACLF was 3 for 3 patients (42.9 %) and 2 for 4 patients (57.1 %). The TPE group had significantly higher levels of bilirubin (392.3 ± 117.1µmol/l vs. 219 ± 185µmol/l , p = 0.04), and INR values (5.7 ± 3.4 vs. 3.5 ± 0.9, p < 0.005) compared to the control group. Patient survival was respectively 28.6 % and 14.3 % at 30 and 90 days in the TPE group and 35.7 % and 7.14 % in the control group respectively (HR: 1 (95 % CI 0.19- 5.2; p = 1). One patient in the TPE group had a liver transplantation 13 days after admission to ICU and is still alive and none in the control group. Two (28.6 %) patients died from complications related to the double lumen catheter used for TPE. CONCLUSION: This pilot study of TPE in patients with ACLF grade 2 and 3 showed a marked but transient improvement in liver function tests. TPE worth to be evaluated in large trials in ACLF patients, with a liver transplant project, and less organ failure.

Synergistic interaction between pH and NaCl in the limits of germination and outgrowth of Clostridium sporogenes and Group I Clostridium botulinum vegetative cells and spores after heat treatment.

Group I Clostridium botulinum and Clostridium sporogenes are physiologically and genetically closely related. Both are widely distributed in the environment and can cause foodborne botulism. In this work, a physiological study was conducted with 37 isolates from spoiled canned food and five referenced strains of C. sporogenes (three isolates) and Group I C. botulinum (two isolates). Growth limits of vegetative cells were established as a function of pH and NaCl concentration in PYG modified medium (PYGm) at 30 °C for 48 days. The heat resistance of the spores was studied for 2 min and 10 min at 102 °C and 110 °C. This physiological study (pH, NaCl growth limits and heat resistance) allowed the selection of 14 isolates of C. sporogenes (twelve isolates) and Group I C. botulinum (two isolates) representative of the diversity found. This panel of 14 selected isolates (11 isolated from spoiled canned food and three reference strains), were whole genome sequenced, but no association of physiological and genetic characteristics could be detected. Finally, we studied the ability of spores to germinate and grow from 5 isolates (four C. sporogenes and one Group I C. botulinum), under stress conditions generated by pH and NaCl following a low intensity heat treatment. The accumulation of these 3 stresses creates synergies that will strongly reduce the probability of spore growth in pH and salt conditions where they usually proliferate. The effect is progressive as the conditions become drastic: the number of decimal reduction observed increases translating a probability of growth which decreases. This study provides a better understanding of the behaviour of C. sporogenes and Group I C. botulinum isolates and shows how the combination of pH, NaCl and heat treatment can help prevent or minimise foodborne botulism outbreaks.

The synergic interaction between environmental factors (pH and NaCl) and the physiological state (vegetative cells and spores) provides new possibilities for optimizing processes to manage risk of C. sporogenes spoilage.

Clostridium sporogenes has been widely used as a surrogate for proteolytic C. botulinum for validating thermal processes in low-acid cans. To limit the intensity of heat treatments, industrials must use other ways of control as an association of acidic and saline environment after a low heat treatment. The probability of growth of pH (7-4.4), sodium chloride concentration (0-11%) and heat treatment (80°C-10 min; 100°C-1.5 min and 5.2 min) were studied on C. sporogenes PA 3679 spores and vegetative cells. Vegetative cells or heat-treated spores were inoculated in PYGm broth at 30 °C for 48 days in anaerobic conditions. Vegetative cells growth (pH 4.6-pH 4.5; 7%-8% NaCl) range is larger than the spore one (pH 5.2-pH 5.0; 6%-7% NaCl). Spores germination and outgrowth rage is decreased if the spores are heat-treated at 100 °C for 1.5 min (pH 5.5-5.3; 4%-5% NaCl) and 5.2 min (pH 5.7-5.3; 4%-5% NaCl). The C. sporogenes PA 3679 spores germination and outgrowth is impacted by their physiological state. The synergic interaction between environmental factors (pH and NaCl) and the physiological state (vegetative cells and spores) opening new possibilities for optimizing food formulation processes to manage the risks of C. sporogenes spoilage.

Viability of bacterial spores surviving heat-treatment is lost by further incubation at temperature and pH not suitable for growth.

Spores from 21 strains from different genera were heat-treated and stored in different sets of process conditions (4 temperatures and 3 pH levels) defined to prevent growth. In these conditions, spores surviving the heat treatment progressively lost viability during storage. Different inactivation curve shapes (linear, shoulder and tailing) and different sensitivities to storage were observed. B. coagulans showed the fastest inactivation kinetics, with more than 4-log reduction of spore population within 24 h after heating and G. stearothermophilus displayed slower inactivation kinetics, whereas all the anaerobic strains studied (M. thermoacetica and Thermoanaerobacterium spp.) proved resistant to storage conditions, with no destruction detected during 90 days in most cases. Inactivation rates were relatively unaffected by sub-lethal pH but sharply accelerated by temperature: Inactivation became faster as temperature increased (in the 8 °C-55 °C temperature range), with growth blocked by low pH in sub-lethal temperatures. There were changes in surviving spore numbers after the heat-treatment phase. This has implications and applications in canned food industries, as the probability of a retorted sample testing as non-stable, meaning possible spoilage, may decrease with time. In simple terms, a batch of low-acid canned food that tests as non-shelf-stable after an incubation test i.e. positive growth conditions, may later become negative if stored at room temperature (below the minimal growth temperature for thermophilic spores), which may change the marketability of the batch.

European survey and evaluation of sampling methods recommended by the standard EN ISO 18593 for the detection of Listeria monocytogenes and Pseudomonas fluorescens on industrial surfaces.

The ready-to-eat products can be contaminated during processing by pathogen or spoilage bacteria, which persist in the industrial environment. Some bacterial species are able to form biofilms which protect them from environmental conditions. To check the bacterial contamination of the surfaces in the food industries, the professionals must regularly use surface sampling methods to detect the pathogen such as Listeria monocytogenes or the spoilage such as Pseudomonas fluorescens. In 2010, we designed and carried out a European survey to collect surface sampling information to detect or enumerate L. monocytogenes in food processing plants. A total of 137 questionnaires from 14 European Union Member States were returned. The outcome of this survey showed that the professionals preferred friction sampling methods with gauze pad, swab and sponges versus contact sampling methods. After this survey, we compared the effectiveness of these three friction sampling methods and the contact plates, as recommended in the standard EN ISO 18593 that was revised in 2018, on the recovery of L. monocytogenes and of P. fluorescens in mono-specie biofilms. This study showed no significant difference between the effectiveness of the four sampling methods to detach the viable and culturable bacterial population of theses mono-specie biofilms.

High pressure sensitization of heat-resistant and pathogenic foodborne spores to nisin.

Today, there is no effective non-thermal method to inactivate unwanted bacterial spores in foods. High-Pressure (HP) process has been shown to act synergistically with moderate heating and the bacteriocin nisin to inactivate spores but the mechanisms have not been elucidated. The purpose of the present work was to investigate in depth the synergy of HP and nisin on various foodborne spore species and to bring new elements of understandings. For this purpose, spores of Bacillus pumilus, B. sporothermodurans, B. licheniformis, B. weihenstephanensis, and Clostridium sp. were suspended in MES buffer, in skim milk or in a liquid medium simulating cooked ham brine and treated by HP at 500 MPa for 10 min at 50 °C or 20 °C. Nisin (20 or 50 IU/mL) was added at three different points during treatment: during HP, during and or in the plating medium of enumeration. In the latter two cases, a high synergy was observed with the inhibition of the spores of Bacillus spp. The evaluation of the germinated fraction of Bacillus spp. spores after HP revealed that this synergy was likely due to the action of nisin on HP-sensitized spores, rather than on HP-germinated spores. Thus, the combination of nisin and HP can lead to Bacillus spp. spore inhibition at 20 °C. And Nisin can act on HP-treated spores, even if they are not germinated. This paper provides new information about the inhibition of spores by the combination of HP and nisin. The high synergy observed at low temperature has not been reported yet and could allow food preservation without the use of any thermal process.

Convergence of Bigelow and Arrhenius models over a wide range of heating temperatures.

The heat resistance of the bacterial spores of Moorella thermoacetica, Clostridium sporogenes, Geobacillus stearothermophilus and Bacillus coagulans was determined over a wide range of temperatures using the capillary method and thermoresistometer Mastia. The results showed that the two experimental methods gave similar heat resistance values excepted for Geobacillus stearothermophilus. The effect of temperature on thermal resistance was evaluated using the Arrhenius and Bigelow models. The fit of the heat sensitivity parameters of the Arrhenius and Bigelow models on the heat resistance parameter values obtained over a wide temperature range was equally good. Despite the apparent mathematical incompatibility of the two equations, it is recognized that they yield the same goodness of fit. This paper finds a mathematical reason for this convergence and explains why inside a temperature range of at least 100 °C, no significant difference in the quality of fit between these two models can be found.

Liver transplantation in patients with liver failure related to exertional heatstroke.

BACKGROUND & AIMS: Severe acute liver injury is a grave complication of exertional heatstroke. Liver transplantation (LT) may be a therapeutic option, but the criteria for LT and the optimal timing of LT have not been clearly established. The aim of this study was to define the profile of patients who require transplantation in this context. METHODS: This was a multicentre, retrospective study of patients admitted with a diagnosis of exertional heatstroke-related severe acute liver injury with a prothrombin time (PT) of less than 50%. A total of 24 male patients were studied. RESULTS: Fifteen of the 24 patients (median nadir PT: 35% [29.5-40.5]) improved under medical therapy alone and survived. Nine of the 24 were listed for emergency LT. At the time of registration, the median PT was 10% (5-12) and all had numerous dysfunctional organs. Five patients (nadir PT: 12% [9-12]) were withdrawn from the list because of an elevation of PT values that mainly occurred between day 2 and day 3. Ultimately, 4 patients underwent transplantation as their PT persisted at <10%, 3 days (2.75-3.25) after the onset of exertional heatstroke, and they had more than 3 organ dysfunctions. Of these 4 patients, 3 were still alive 1 year later. Histological analysis of the 4 explanted livers demonstrated massive or sub-massive necrosis, and little potential for effective mitoses, characterised by a "mitonecrotic" appearance. CONCLUSION: The first-line treatment for exertional heatstroke-related severe acute liver injury is medical therapy. LT is only a rare alternative and such a decision should not be taken too hastily. A persistence of PT <10%, without any signs of elevation after a median period of 3  days following the onset of heatstroke, was the trigger that prompted LT, was the trigger adopted in order to decide upon LT. LAY SUMMARY: Acute liver injury due to heatstroke can progress to acute liver failure with organ dysfunction despite medical treatment; in such situations, liver transplantation (LT) may offer a therapeutic option. The classic criteria for LT appear to be poorly adapted to heatstroke-related acute liver failure. We confirmed thatmedication is the first-line therapy acute liver injury caused by heatstroke, with LT only rarely necessary. A decision to perform LT should not be made hastily. Fluctuations in prothrombin time and the patient's clinical status should be considered even in the event of severe liver failure.

Temperature impacts the sporulation capacities and spore resistance of Moorella thermoacetica.

Temperatures encountered in cannery allow growth of thermophilic spore-forming bacteria, including the strictly anaerobe Moorella thermoacetica, which grows optimally from 55 °C to 65 °C and is the main cause of spoilage of low-acid canned foods (LACFs) at high temperature. Resistance to wet-heat, biocides and UV-C of spores formed at different temperatures was assessed either for a selection of M. thermoacetica strains or for the strain M. thermoacetica ATCC 39073. Spores formed at 45 °C were significantly more sensitive to wet-heat than spores produced at 55 °C, while spores produced at 65 °C were as heat-resistant as spores produced at 55 °C. Spores of M. thermoacetica ATCC 39073 produced at 45 °C were significantly less resistant to peracetic acid than spores formed at 55 °C, while no difference in sensitivity to H2O2 or to UV-C treatment was observed whatever the sporulation temperature. However, both types of treatment enabled at least a 3.3 log CFU/mL reduction of M. thermoacetica ATCC 39073 spores. M. thermoacetica spores thus showed higher resistance properties when sporulation temperature was close to optimal growth temperature. These findings suggest food spoilage due to M. thermoacetica species could be controllable by holding temperatures below optimal growth temperature from the blanching step to the can filling step.

[From the perinatal period to adolescence: the three stages of coordination]. / De la périnatalité à l'adolescence : trois temps d'articulation.

The need for coordinated organisation between infant-child psychiatry and adult psychiatry is highlighted through key periods, with the aid of a clinical case: the perinatal period and the hospitalisation of a mother with her child; the psychiatric support of the unwell mother and that of her daughter; then the transition for the 16-year-old teenager towards adult psychiatry. Taking into consideration the mother-child bond is essential and requires collaborative care projects, the creation of opportunities for joint reflection and organisation, and the acknowledgement that internal institutional divisions exist which are too often denied.

Spore-forming bacteria responsible for food spoilage.

This review explores the main spore-forming bacteria involved in the spoilage of various processed foods. Bakery products are specifically spoiled by Bacillus species, the dominant one being Bacillus amyloliquefaciens, while different Clostridium species classically contaminate refrigerated vacuum-packed meats. These two genera have also been isolated from milk products, even when milk is pasteurized, sterilized, dehydrated or fermented, according to heat treatment and storage temperature. Finally, the most heat-resistant microorganisms are isolated in low-acid canned foods, the three predominant species being Geobacillus stearothermophilus, Moorella thermoacetica and Thermoanaerobacterium spp.

Risk assessment of proteolytic Clostridium botulinum in canned foie gras.

In this study, a risk assessment of proteolytic Clostridium botulinum in canned foie gras was performed, the number of illnesses per year in France due to C. botulinum in foie gras was estimated. Data on initial level in raw materials were collected at manufacturers and analysed using a Negative Binomial distribution. The effect of the usual foie gras heat treatment (equivalent time at 121 °C: F0=0.5 min) was considered at two levels: first, it led to an inactivation (estimated to 2.3 log); second it led to a spore injury and then to a spore inhibition. This latter effect was assessed by analysing data from a challenge test study carried out with Clostridium sporogenes spores in the foie gras product. The probability of spore recovering after thermal inhibition was estimated to 9.5×10(-8) (corresponding to 7.0 log). The data on the consumption pattern were collected on the French market. The Quantitative Microbiological Risk Assessment (QMRA) model and all the assumptions are reported in detail in the study. The initial contamination of raw materials, effect of thermal treatment on microbial inactivation and spore inhibition were handled mathematically using a probabilistic framework, considering only the variability dimension. The model was implemented in Excel and run through Monte Carlo simulation, using @Risk software. In parallel, epidemiological data collected from the French Institute for Public Health Surveillance during the period 2001-2012 were used to estimate an Appropriate Level Of Protection (ALOP) and then a Food Safety Objective (FSO): ALOP equalled to 2.5×10(-3) illnesses per million inhabitant per year, FSO equalled to 1.4×10(-9) foie gras portions containing C. botulinum spore (expressed in decimal logarithm, FSO=-8.9). The QMRA model output values were smaller, but on the same order of magnitude as these two figures: 8.0×10(-4) illnesses per million inhabitants per year, and, 4.5×10(-10) (-9.3 log) foie gras portions containing C. botulinum spores able to recover. It was then possible to conclude that the current practices regarding thermal treatment of canned foie gras are sufficient to control the risk of C. botulinum in foie gras in France.

Contamination pathways of spore-forming bacteria in a vegetable cannery.

Spoilage of low-acid canned food during prolonged storage at high temperatures is caused by heat resistant thermophilic spores of strict or facultative bacteria. Here, we performed a bacterial survey over two consecutive years on the processing line of a French company manufacturing canned mixed green peas and carrots. In total, 341 samples were collected, including raw vegetables, green peas and carrots at different steps of processing, cover brine, and process environment samples. Thermophilic and highly-heat-resistant thermophilic spores growing anaerobically were counted. During vegetable preparation, anaerobic spore counts were significantly decreased, and tended to remain unchanged further downstream in the process. Large variation of spore levels in products immediately before the sterilization process could be explained by occasionally high spore levels on surfaces and in debris of vegetable combined with long residence times in conditions suitable for growth and sporulation. Vegetable processing was also associated with an increase in the prevalence of highly-heat-resistant species, probably due to cross-contamination of peas via blanching water. Geobacillus stearothermophilus M13-PCR genotypic profiling on 112 isolates determined 23 profile-types and confirmed process-driven cross-contamination. Taken together, these findings clarify the scheme of contamination pathway by thermophilic spore-forming bacteria in a vegetable cannery.

Meta-analysis of D-values of proteolytic Clostridium botulinum and its surrogate strain Clostridium sporogenes PA 3679.

Foodborne botulism is a serious disease resulting from ingestion of preformed Clostridium botulinum neurotoxin in foodstuff. Since the 19th century, the heat resistance of this spore forming bacteria has been extensively studied in order to guarantee the public health associated with low acidic, ambient stable products. The most largely used heat resistance parameters in thermal settings of such products are the D121.1°C values (time required to have a 10-fold decrease of the spore count, at 121.1°C) and the z-values (temperature increase to have a 10-fold decrease of D-values). To determine D121.1°C and z-values of proteolytic C. botulinum and its nontoxigenic surrogate strain C. sporogenes PA3679, a dataset of 911 D-values was collected from 38 scientific studies. Within a meta-analysis framework, a mixed-effect linear model was developed with the log D-value (min) as response and the heat treatment temperature as explicative variable. The studies (38), the C. botulinum strains (11), and the heat treatment media (liquid media and various food matrices, split into nine categories in total) were considered as co-variables having a random effect. The species (C. botulinum and C. sporogenes) and the pH (five categories) were considered as co-variables having a fixed effect. Overall, the model gave satisfactory results with a residual standard deviation of 0.22. The heat resistance of proteolytic C. botulinum was found significantly lower than the C. sporogenes PA 3679 one: the mean D-values at the reference temperature of 121.1°C, in liquid media and pH neutral, were estimated to 0.19 and 1.28min for C. botulinum and C. sporogenes, respectively. On the other hand, the mean z-values of the two species were similar: 11.3 and 11.1°C for C. botulinum and C. sporogenes, respectively. These results will be applied to thermal settings of low-acid ambient stable products.

Quantitative assessment of the risk of microbial spoilage in foods. Prediction of non-stability at 55 °C caused by Geobacillus stearothermophilus in canned green beans.

Microbial spoilage of canned foods by thermophilic and highly heat-resistant spore-forming bacteria, such as Geobacillus stearothermophilus, is a persistent problem in the food industry. An incubation test at 55 °C for 7 days, then validation of biological stability, is used as an indicator of compliance with good manufacturing practices. We propose a microbial risk assessment model predicting the percentage of non-stability due to G. stearothermophilus in canned green beans manufactured by a French company. The model accounts for initial microbial contaminations of fresh unprocessed green beans with G. stearothermophilus, cross-contaminations in the processing chain, inactivation processes and probability of survival and growth. The sterilization process is modeled by an equivalent heating time depending on sterilization value F0 and on G. stearothermophilus resistance parameter z(T). Following the recommendations of international organizations, second order Monte-Carlo simulations are used, separately propagating uncertainty and variability on parameters. As a result of the model, the mean predicted non-stability rate is of 0.5%, with a 95% uncertainty interval of [0.1%; 1.2%], which is highly similar to data communicated by the French industry. A sensitivity analysis based on Sobol indices and some scenario tests underline the importance of cross-contamination at the blanching step, in addition to inactivation due to the sterilization process.

[Partnership around difficult teenagers in Brest]. / Partenariat autour des adolescents difficiles à Brest.

The issues surrounding difficult teenagers results in professionals formalising a partnership. Certain areas of focus are identified such as getting to know each other better in order to understand each other better, working in a "common language", understanding professional identities, or embracing long term partnership. Pressure to assess and rationalise spending, as well as political challenges, must be taken into consideration.

[Suicidal behavior in children]. / Conduites suicidaires chez l'enfant.

Because of the rarity of suicide and attempted suicide in young children the subject is not commonly studied and is quite poorly understood. Indeed, we have longed denied the possibility of a young child's enactment of a suicidal desire. The myth of total childhood innocence paired with societal views on death and mourning make suicide at this age unacceptable and furthermore, unthinkable. Everything is positioned towards denial; however suicidal behaviour does exist in children and we can identify specifics surrounding the methods used, and their meaning in both the social and environmental contexts in which they take place. Within the following we will suggest and provide tools for prevention and treatment.

[Bipolar disorders in children and adolescents]. / Trouble bipolaire de l'enfant et de l'adolescent.

While difficult, early detection of bipolar disorders in children and adolescents is crucial. Depending on age, diagnosis may be more or less difficult. Family history and the environment must also be taken into account.