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Liver biopsy was performed in 38 patients with fulminant hepatitis and coma and repeated in 22. Stereological estimation of hepatocyte volume was correlated with levels of clotting factors. Early liver biopsy allowed prognosis in 55% of the cases. All patients with a hepatocyte volume of <35% and thromboplastin time ≤10% died; all patients but two with hepatocyte volume ≥35% and thromboplastin time >10% recovered consciousness (n = 9) or at least showed evidence of marked liver regeneration (n = 2). On serial liver biopsy a significant increase in hepatocyte volume and clotting factors was only observed in patients who recovered consciousness. The estimated liver cell mass after regeneration in patients who recovered consciousness was ≥45% and <45% in the patients who did not. [ABSTRACT FROM PUBLISHER]

Acinetobacter baumannii, classified as priority number one by the World Health Organization (WHO), is an opportunistic pathogen responsible for infection and is able to develop antibiotic resistance easily. Membranes are bacteria's first line of defense against external aggression, such as antibiotics. A chemical modification of a lipid family or a change in lipid composition can lead to resistance to antibiotics. In this work, we analyzed different A. baumannii strains from various environments with different antibiotic resistance profiles, using matrix-assisted laser desorption ionization-Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FT-ICR MS). This study shows that it is possible to describe the main lipidome (phospholipids and lipid A) from the simple preparation of lysed cells, and that despite the complexity of the mixture. This ultra-high resolution mass spectrometry technique enables the separation of isobaric ion, to report a new class of lipids. Given its performance, this technique can be used to quickly and reliably characterize the lipidome of clinical strains from different environments., Competing Interests: Declaration of competing interest The authors declare no competing interest concerning the research authorship and or publication of this article., (Copyright © 2024 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Persister cells constitute a bacterial subpopulation able to survive to high concentrations of antibiotics. This phenotype is temporary and reversible, and thus could be involved in the recurrence of infections and emergence of antibiotic resistance. To better understand how persister cells survive to such high antibiotic concentration, we examined changes in their lipid composition. We thus compared the lipidome of Acinetobacter baumannii ATCC 19606 T persister cells formed under ciprofloxacin treatment with the lipidome of control cells grown without antibiotic. Using matrix assisted laser desorption ionisation-Fourier transform ion cyclotron resonance mass spectrometry, we observed a higher abundance of short chains and secondary chains without hydroxylation for lipid A in persister cells. Using liquid chromatography-tandem mass spectrometry, we found that persister cells produced particular phosphatidylglycerols, as LPAGPE and PAGPE, but also lipids with particular acyl chains containing additional hydroxyl group or uncommon di-unsaturation on C18 and C16 acyl chains. In order to determine the impact of these multiple lipidome modifications on membrane fluidity, fluorescence anisotropy assays were performed. They showed an increase of rigidity for the membrane of persister cells, inducing likely a decrease membrane permeability to protect cells during dormancy. Finally, we highlighted that A. baumannii persister cells also produced particular wax esters, composed of two fatty acids and a fatty diol. These uncommon storage lipids are key metabolites allowing a rapid bacterial regrow when antibiotic pressure disappears. These overall changes in persister lipidome may constitute new therapeutic targets to combat these particular dormant cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The emergence of multi-drug resistant pathogens is a major public health problem, leading us to rethink and innovate our bacterial control strategies. Here, we explore the antibiofilm and antivirulence activities of nineteen 6-polyaminosterol derivatives (squalamine-based), presenting a modulation of their polyamine side chain on four major pathogens, i.e., carbapenem-resistant A. baumannii (CRAB) and P. aeruginosa (CRPA), methicillin-resistant S. aureus (MRSA), and vancomycin-resistant E. faecium (VRE) strains. We screened the effect of these derivatives on biofilm formation and eradication. Derivatives 4e (for CRAB, VRE, and MRSA) and 4f (for all the strains) were the most potent ones and displayed activities as good as those of conventional antibiotics. We also identified 11 compounds able to decrease by more than 40% the production of pyocyanin, a major virulence factor of P. aeruginosa . We demonstrated that 4f treatment acts against bacterial infections in Galleria mellonella and significantly prolonged larvae survival (from 50% to 80%) after 24 h of CRAB, VRE, and MRSA infections. As shown by proteomic studies, 4f triggered distinct cellular responses depending on the bacterial species but essentially linked to cell envelope. Its interesting antibiofilm and antivirulence properties make it a promising a candidate for use in therapeutics.

A series of 6-polyaminosteroid analogues of squalamine were synthesized with moderate to good yields and evaluated for their in vitro antimicrobial properties against both susceptible and resistant Gram-positive (vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus ) and Gram-negative (carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains. Minimum inhibitory concentrations against Gram-positive bacteria ranged from 4 to 16 µg/mL for the most effective compounds, 4k and 4n , and showed an additive or synergistic effect with vancomycin or oxacillin. On the other hand, the derivative 4f , which carries a spermine moiety like that of the natural trodusquemine molecule, was found to be the most active derivative against all the resistant Gram-negative bacteria tested, with an MIC value of 16 µg/mL. Our results suggest that 6-polyaminosteroid analogues of squalamine are interesting candidates for Gram-positive bacterial infection treatments, as well as potent adjuvants to fight Gram-negative bacterial resistance.

Acinetobacter baumannii has emerged as one of the most problematic bacterial pathogens responsible for hospital-acquired and community infections worldwide. Besides its high capacity to acquire antibiotic resistance mechanisms, it also presents high adhesion abilities on inert and living surfaces leading to biofilm development. This lifestyle confers additional protection against various treatments and allows it to persist for long periods in various hospital niches. Due to their remarkable antimicrobial tolerance, A. baumannii biofilms are difficult to control and ultimately eradicate. Further insights into the mechanism of biofilm development will help to overcome this challenge and to develop novel antibiofilm strategies. To unravel critical determinants of this sessile lifestyle, the proteomic profiles of two A. baumannii strains (ATTC17978 and SDF) grown in planktonic stationary phase or in mature solid-liquid (S-L) biofilm were compared using a semiquantitative proteomic study. Of interest, among the 69 common proteins determinants accumulated in the two strains at the S-L interface, we sorted out the MacAB-TolC system. This tripartite efflux pump played a role in A. baumannii biofilm formation as demonstrated by using Δ macAB-tolC deletion mutant. Complementary approaches allowed us to get an overview of the impact of macAB-tolC deletion in A. baumannii physiology. Indeed, this efflux pump appeared to be involved in the envelope stress response occurring in mature biofilm. It contributes to maintain wild type (WT) membrane rigidity and provides tolerance to high osmolarity conditions. In addition, this system is probably involved in the maintenance of iron and sulfur homeostasis. MacAB-TolC might help this pathogen face and adapt to deleterious conditions occurring in mature biofilms. Increasing our knowledge of A. baumannii biofilm formation will undoubtedly help us develop new therapeutic strategies to tackle this emerging threat to human health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Robin, Nicol, Le, Tahrioui, Schaumann, Vuillemenot, Vergoz, Lesouhaitier, Jouenne, Hardouin, Potron, Perrot and Dé.)

This procedure is well known, there were 2 000 cases reported in the literature with a very small number of complications. Is autotransfusion really efficacious? According to the author's results in 9 cases of hemoperitoneum, the red cells obtained by this method are quantitatively valid, but hemolysis starts early (6 hours) and the disappearance of the platelets and coagulation factors occurs even more early (2 hours). However, clinical tolerance is perfect, thus confirming the good experimental results obtained in animals. The true limits are hemolysis and the risk of contamination but, with appropriate apparatus and precise indications, and unsoiled blood, less than 24 hours old, autotransfusion is a good method which may provide a solution in certain emergencies.

In phlebology, an anticoagulant treatment is usually called for in the fight against thrombosis. The favourable short-term development of most phlebites means that an anticoagulant treatment should not be used unless there are serious risks involved in the various complications observed. This treatment may therefore be used, on condition that diagnosis is certain, that the risks involved are serious enough; the least restrictive, least expensive form of treatment is preferable, provided that it is as effective, of course; the conditions of applications should be scrupulously upheld: no contraindications, the cooperation of the patient, quality of the biological controls etc. If these conditions are respected, the anticoagulant treatment combines efficiency and safety to a degree which places it foremost among anti-thrombotic methods, after physiotherapy.

Pseudo-tumoral blood collections in haemophiliacs are uncommon but must be borne in mind because of their severity and of the need for timely and appropriate treatment. Surgical excision appears to be required as soon as the tendency towards enlargement is recognized and before the volume and complications of the tumour increase the difficulties, particularly in the iliac fossa. Other treatments, especially puncture-aspiration, seem to be ineffective and/or dangerous. A better knowledge of the pathogenic processes involved might lead to new therapeutic approaches.

Antivitamins K remain the anticoagulant of choice when treatment lasts several days, because they can be ingested orally, and they require relatively in frequent laboratory tests, and because of the absence of any superior haematological treatments for thrombosis. Physiological studies have explained the effects on the anticoagulant action of the antivitamins K, of imbalance of the intestinal microbial flora and of pathological changes in diuresis. This knowledge is indispensable for national treatment. Surveillance by means of laboratory tests remains indispensable but continues to pose practical problems, as non-specialized biologists have difficulty in achieving the necessary basic conditions (quality of venous puncture, control and test...). Determination of the Quick time remains the most practical method. Laboratory determination of the different constituents of the prothrombin complex makes it possible to regulate perfectly the treatment with antivitamins K of a patient who is also receiving heparin.

There are, as well as the more common coagulopathies such as deficiency in antithrombin III or Protein C, certain rare disorders complicated simultaneously by haemorrhage and thrombosis--such as dysfibrinogenemia--which can present very special therapeutic problems.

Giant haemangiomas combined with a haemostasis disorder of the Kasabach-Meritt type are rare and even more rare are the problems posed during labour when vulvo-vagino-uterine sites are involved. Two cases are reported. After summary of the clinical and biochemical studies, the authors report attempts to improve the haemostasis disorder, first with heparin and then with antifibrinolytic preparations, and to improve the angiomas with antifibrinolytic preparations in the hope of stimulating intrasacular thrombosis. In particular, the obstetric and surgical problems are discussed in the context of labour. In one case the outcome of labour was successful only moderate transfusion being required, and in the other the outcome was fatal despite the use of about 100 bottles of blood in the first 24 hours. In both cases the infants were normal.

Two cases of resistance to the heparin treatment, induced by large consumption of antithrombin III, are reported. Normally small, this consumption does not automatically call for the systematic dosage of Antithrombin III for each treatment using heparin. On the other hand, any clinical or biological resistance to higher doses of heparin, any personal or family history of thrombosis necessitate the administration of Antithrombin III. Where there is an acquired or congenital deficit, an injection of Antithrombin III corrects the disorder and reduces the risk of thrombosis. In the case of a heparin-antivitamin K relay, it is essential to achieve complete biological effectiveness of the antivitamins K to interrupt the administration of the heparin.

The authors report the case of a young woman aged 29, mother of 2 children, presenting a post-phlebitic syndrome with hyperalgic capillaritic ulcer, a 10 year history of serious thrombophlebitic episodes with repeated pulmonary embolism despite heparin therapy, and reports of similar episodes in the family, some of which proved fatal. Haematological study showed a clear diminution in progressive antithrombin activity. A discussion follows on the clinical and haematological aspects of this constitutional and familial deficiency, which has been known since 1965 (Egelberg). The relative rarity of this condition should not prevent the routine search (by combined functional, immunological and chromogenic estimation) in the presence of repeated thrombosis, and when the thrombosis is biologically resistant to heparin : in such cases, the indication for long term treatment with vitamin K antagonists is undeniable.

Therapeutic fibrinolysis represents the only logical means of curing thromboses, by assuring the destruction of the thrombus. This kind of therapy, which was introduced clincally over 10 years ago, has been used on only a limited scale because of the high risk of haemorrhage and the need for highly specialized laboratory control tests. Different methods of administration, overcoming one or other of these disadvantages, have resulted recently in its wider use but this has been accompanied by a reduction in efficacity. The very satisfactory clinical results obtained in some cases remain limited and thus in this context the indications should not be restricted.

Progress made in the field of haemostasis 30 years ago was essentially to do with the identification of the different activators of coagulation, the deficits of which provoke hemorrhage. Over the last ten years, progress has been made which is of benefit to research into thrombosis. This wave of progress, still in its infancy, aids both the understanding of the mechanisms involved, and the treatment of thrombosis. The role of the deficits reducing coagulation in the occurrence of thromboses is the most distinctive if not unique, fact. The molecular study of the factors of coagulation constitutes another aspect of recent progress; this gives a better understanding of the pathological phenomena and anticoagulant behaviour. Examples are given of this progress in molecular study and in the aetiological diagnosis of thrombosis.

Major mesenteric venous thrombosis in a young man who had already had spontaneous thromboembolic accidents prompted the diagnosis in 1982 of 'Antithromin III' deficiency. The initial reduction of this inhibitor proved to be secondary to a consumption raised abnormally by Heparin. Research into the family antecedents made it possible in 1983 to discover a constitutional 'Protein C' deficiency without stopping the antivitamins K for this patient.

Clinical and biological studies were carried out in 21 subjects one to twenty-three years after the injured spleen had been removed. Asplenia did not give rise to clinical symptoms, did not facilitate infections and had no effect on growth. Laboratory investigations revealed a decrease in IgM in 6 subjects and minor quantitative and qualitative platelet abnormalities. The absence of Jolly's bodies in 7 subjects was suggestive of spleen regeneration, which was confirmed by scintigraphy in 2 cases. The significance of these findings in discussed.