[Kidney injury in COVID-19]. / Atteintes rénales de la COVID-19.

The SARS-CoV-2 virus causes a respiratory distress syndrome, the main symptom of COVID-19 (for "COronaVIrus Disease 2019"). This infectious disease has been causing a major health and socio-economic pandemic since December 2019. The pulmonary alveolus is regarded as the main target of SARS-CoV-2. However, this coronavirus is capable of directly or indirectly affecting other organs, including the kidneys. Here, we summarize the presumed pathophysiology of COVID-19 renal disease. The incidence of acute kidney injury ranges from 0,5 to 22 % of all patients infected with SARS-CoV-2. The need for renal replacement therapy is reported in 5-9 % of patients in intensive care. Histological analysis of renal biopsies mainly shows acute tubular necrosis of varying severity, as well as the congestion of glomerular and peri-tubular capillaries. Endothelitis has been described in few cases. Evidence for a factual inflammation of the glomerulus remains controversial. The medium/long term consequences of COVID-19 nephropathy are unknown and will deserve a tight follow-up.

Le virus SARS-CoV-2 provoque un syndrome de détresse respiratoire aiguë, le symptôme principal de l'infection COVID-19 (pour «COronaVIrus Disease 2019¼). Cette maladie infectieuse provoque une pandémie de gravité sanitaire et socio-économique majeure depuis décembre 2019. La cible principale du SARS-CoV-2 serait l'alvéole pulmonaire. Néanmoins, ce coronavirus est capable d'affecter directement ou indirectement d'autres organes, y compris les reins. Nous résumons ici la physiopathologie présumée de l'atteinte rénale de la COVID-19. L'incidence de l'insuffisance rénale aiguë varie entre 0,5 à 22 % de tous les patients infectés par le SARS-CoV-2. La nécessité d'une épuration extra-rénale est rapportée chez 5-9 % des patients pris en charge aux soins intensifs. L'analyse histologique de biopsies rénales montre, principalement, une nécrose tubulaire aiguë de sévérité variable, ainsi qu'une congestion des capillaires glomérulaires et péri-tubulaires. Une endothélite a parfois été décrite. L'atteinte inflammatoire du glomérule reste débattue. Les conséquences à moyen/long termes de la néphropathie COVID-19 sont inconnues et mériteront un suivi étroit.

[Arguments for a role of the gut microbiota in the pathophysiology of hypertension]. / Arguments en faveur d'un rôle du microbiote intestinal dans la physiopathologie de l'hypertension artérielle.

The gut microbiota refers to the community of microorganisms living in the mammalian digestive tract. Over the past decades, numerous preclinical and clinical studies have suggested that gut microbiota is involved in the physiological homeostasis of the host, particularly in the immune and metabolic systems. Furthermore, the dysfunction of gut microbiota, also called "dysbiosis", has been associated with various diseases, such as the metabolic syndrome or chronic kidney disease. In this review, we summarize the knowledge about the possible role of gut microbiota in the development of arterial hypertension. We detail the pathophysiological mechanisms, namely involving short-chain fatty acids produced by the bacterial fermentation of food carbohydrates. These metabolites are reabsorbed by the intestinal mucosa and interact with a multitude of G-protein coupled receptors at the surface of cells involved in blood pressure regulation, including renal tubular cells. These observations open up innovative diagnostic and therapeutic approaches in arterial hypertension, which is a major public health problem.

Le microbiote intestinal désigne la communauté des micro-organismes vivant dans le tube digestif des mammifères. Au cours des dernières années, de nombreuses études précliniques et cliniques ont suggéré que le microbiote intestinal est impliqué dans la régulation physiologique de l'hôte, notamment au niveau des systèmes immunitaires et métaboliques. Bien plus, le dysfonctionnement du microbiote intestinal, également appelé la dysbiose, a été associé à diverses maladies, telles que le syndrome métabolique ou l'insuffisance rénale chronique. Dans la présente revue, nous résumons l'état des connaissances à propos du possible rôle du microbiote intestinal dans le développement de l'hypertension artérielle. Nous en détaillons les mécanismes physiopathologiques impliquant, notamment, les acides gras à chaîne courte produits par la fermentation bactérienne des hydrates de carbone alimentaires. Ces métabolites sont réabsorbés par la muqueuse intestinale et interagissent avec une multitude de récepteurs couplés aux protéines G présents à la surface des cellules impliquées dans la régulation tensionnelle, telles que les cellules tubulaires rénales. Ces observations ouvrent de nouvelles voies diagnostiques et thérapeutiques dans un domaine de santé publique majeur qu'est l'hypertension artérielle.

[Acute myocardial infarction due to polycythemia vera]. / Syndrome coronarien aigu lié à une maladie de Vaquez.

We report the clinical case of a patient presenting with an acute myocardial infarction with ST- segment elevation. The patient is affected by polycythemia vera for many years and doesn't have any other cardiovascular risk factors. The frequency of thrombotic events in polycythemia vera (and more particularly myocardial infarction), their predictive factors, pathophysiology and treatment will be discussed.

Nous présentons le cas clinique d'un patient ayant présenté un infarctus aigu du myocarde avec sus-décalage du segment ST dans un contexte de polycythémie vraie (maladie de Vaquez) diagnostiquée plusieurs années auparavant. Le patient ne présente aucun autre facteur de risque cardio-vasculaire. La fréquence des événements thrombotiques (et plus particulièrement des infarctus du myocarde) chez les patients atteints de polycythémie vraie, les facteurs prédictifs de ces derniers, leur physiopathologie et le traitement à proposer seront discutés.

[Management of hypophosphatemia: a case report]. / Le cas clinique du mois. Prise en charge d'une hypophosphatemia.

Hypophosphatemia is defined by a serum phosphate level lower than 0.8 mmol/l. If hypophosphatemia is chronically maintained, it is associated with muscular, osteous, neurological or cardio-respiratory disorders. We describe a patient with isolated hypophosphatemia, detail the mechanisms of phosphate homeostasis, and envisage the differential diagnosis of hypophosphatemia. Furthermore, we propose a sequential decisional algorithm based on basic biological tests and few complementary investigations. Treatment options are reviewed.

Proteomics applied to transfusion plasma: the beginning of the story.

'Safe blood' is and has always been the major concern in transfusion medicine. Plasma can undergo virus inactivation treatments based on physicochemical, photochemical or thermal methodologies for pathogen inactivation. The validation of these treatments is essentially based on clottability assays and clotting factors' titration; however, their impact on plasma proteins at the molecular level has not yet been evaluated. Proteomics appears as particularly adapted to identify, to localize and, consequently, to correlate these modifications to the biological activity change. At the crossroads of biology and analytical sciences, proteomics is the large-scale study of proteins in tissues, physiological fluids or cells at a given moment and in a precise environment. The proteomic strategy is based on a set of methodologies involving separative techniques like mono- and bidimensional gel electrophoresis and chromatography, analytical techniques, especially mass spectrometry, and bioinformatics. Even if plasma has been extensively studied since the very beginning of proteomics, its application to transfusion medicine has just begun. In the first part of this review, we present the principles of proteomics analysis. Then, we propose a state of the art of proteomics applied to plasma analysis. Finally, the use of proteomics for the evaluation of the impact of storage conditions and pathogen inactivation treatments applied to transfusion plasma and for the evaluation of therapeutic protein fractionated is discussed.

[Tuberculous otomastoiditis: advantage of MRI in the treatment survey]. / Otomastoïdite tuberculeuse: intérêt de l'IRM dans le suivi thérapeutique.

PURPOSE: Mycobacterium tuberculosis is a rare cause of otomastoiditis, accounting for less than a percent of chronic otitis media. The diagnosis is difficult and typically delayed because most physicians are unfamiliar with its presenting features and special laboratory requirements. Such delayed diagnosis leads to delayed treatment onset, and thus, increases complications frequency as irreversible hearing loss, facial palsy or meningo-encephalitis complications. Moreover non specific CT findings do not allow any accurate evaluation of inner ear lesions initially and under treatment. CASE REPORT: We described the first case of MRI of tuberculous mastoiditis and the evolution over a 2-years follow-up period. A patient with a clinical history of chronic otorrhea, resistant to conventional therapy, was referred to our department. CT and MRI permitted to describe the initial lesions and to appreciate the medical treatment efficiency (in order to perform surgery in case of failure or complications). Under medical treatment, MRI showed abscess volume decrease at three months while CT was still unchanged. Remineralization only was observed on CT at 12 months. The patient's healing was obtained after 15 months of antituberculous medication. CONCLUSION: MRI has the advantage over CT to demonstrate directly abscess collections that superimposed to areas of bone destructions within the temporal bone. Initially, MRI allows an accurate evaluation of abscess collections and possible meningo-encephalitis complications. Moreover, MRI precises earlier than CT the improvement of lesions and the efficacy of medical treatment, and thus, permitting us to postpone surgery where it is unnecessary.

[Novel criteria for assessing red blood cell viability in blood banks]. / Nouveaux critères d'évaluation de la viabilité des hématies destinées à la transfusion.

UNLABELLED: In light of recent results on the mechanism of programmed cell death of human red blood cells (RBC), the aim of the present study was to solve the enigma of the rapid clearance of transfused RBCs. MATERIALS AND METHODS: We describe new criteria of RBC viability founded on the use of flow cytometry. They were applied, in association with the classical ones: ATP and hemolysis measurements, to RBCs stored in SAGM medium for 42 days. RESULTS AND CONCLUSIONS: Application of an original method of flow cytometric quantitation of in vitro erythrophagocytosis showed that an important proportion of stored RBCs were phagocytized although the following classical signals for phagocytosis were absent, i.e.: desialylation, phosphatidylserine exposure in the outer leaflet of the RBC membrane, loss of CD47 receptor, an antiphagocytosis signal. In addition, ATP was still present and hemolysis was very low. This enigma was solved by the use of scanning electron microscopy, which showed the disappearance of discocytes and the presence of an important proportion of spheroechinocytes, which are the phagocytable forms of RBCs. The mechanism of this dramatic morphological transformation remains to be elucidated.

Two red blood cell units collected in SAG-M additive solution with the ALYX component collection system.

The first protocol available for the new ALYX component system (Baxter Healthcare Inc.) allows automated collection of two Red Blood Cell (RBC) units from one donor. The primary objective of our evaluation was to assess donor safety, comfort and to check the quality of blood products collected. 30 procedures were performed on eligible donors according to French best donation practices. Eligibility criteria were defined in order to ensure a post donation hemoglobin concentration of 11 g/dL minimum. Pre donation ferritin level was also checked. 360 ml of absolute RBC were collected from each donor. Donors physiological parameters and haematological profile were measured immediately before and after donation. Adverse events and donors were observed during the procedure and followed daily during 5 days after donation. Hemolysis in RBC was followed until of shelf life (<0.8% on 42 days storage). The evaluation of different parameters during storage show no difference if we compare with the manual technique. The concentration of hemoglobin is good and all ou concentrates are conform. No serious adverse effects were reported during and after donation. All donors confirmed they would agree to donate 2 RBC units again with this system. We have seen a good quality of RBC products. This evaluation indicates that 2 RBC donation is feasible on the ALYX system, comfortable and safe for eligible donors.

[Ethics, motivations of plasmapheresis donors]. / Ethiques, motivations des donneurs d'aphérèse plasmatique.

For 50 years, the French Blood Transfusion Service has been developing ethical concepts of anonymous, voluntary and non-profit donation. The subject of this work is the study of ethical aspects and motivations of plasmapheresis donors. Three hundred donors were questioned on these subjects. The questionnaire was created after analysing the semi-orientated interviews of ten donors. The donors are male, aged over 35, with relatively high social and professional backgrounds. The main reason given for the first donation is the request by a relative or another person. With regards to further donations, solidarity with patients is mentioned as a reason. Even if the majority of the donors are aware of the ethical aspects of donation, over 50% of them accept to give plasmapheresis regardless of these principles. Plasmapheresis donors are primarily motivated by solidarity reasons. Thereby, they are fully active in the evolution of society.

Chromatographic purification and properties of a therapeutic human protein C concentrate.

Protein C deficiency (inherited and acquired) has a relatively high incidence rate in the general population worldwide. For many years, protein C deficient patients have been treated with fresh frozen plasma, prothrombin complex concentrates, heparin or oral anticoagulants, which all have clinical drawbacks. We report the production process of a highly purified human protein C concentrate from 1500 l of cryo-poor plasma by a four-step chromatographic procedure. After DEAE-Sephadex adsorption, protein C was separated from clotting factors II, VII and IX by DEAE-Sepharose FF and further purified, using a new strategy, by an on-line chromatographic system combining DMAE-Fractogel and heparin-Sepharose CL-6B. In addition, the product was treated against viral risks by solvent-detergent and nanofiltration on 15-nm membranes. The protein C concentrate was essentially free of other vitamin K-dependent proteins. Proteolytic activity was undetectable. Neither activated protein C, prekallikrein activator, nor activated vitamin K-dependent clotting factors were found resulting in good stability of the protein C activity. In vitro and in vivo animal tests did not reveal any sign of potential thrombogenicity. The final freeze-dried product had a mean protein C concentration of 58 IU/ml and a mean specific activity of 215 IU/mg protein, corresponding to over 12000-fold purification from plasma. Therefore, this concentrate appears to be of potential benefit for the treatment of protein C deficiency.

[Gadolinium in arteriography and interventional radiology: 39 patients]. / Le gadolinium en artériographie et en radiologie interventionnelle: à propos de 39 patients.

OBJECTIVE: To report the experience of using various Gadolinium chelates as contrast media in digital subtraction angiography in patients with relative or absolute contraindications for iodinated contrast agents. MATERIAL: and Methods. Forty-two arteriograms were performed in 39 consecutive patients using Gadolinium chelates (gadoteridol, gadodiamide, and gadopentetate dimeglumine). The vasculature of the brain, of the upper and lower limbs and the renal arteries were examined. Among these 39 patients, 17 were treated by various endovascular procedures. RESULTS: In 40 examinations out of 42, the angiographic result was satisfactory, allowing either a diagnostic evaluation or an endovascular therapeutic procedure. Clinical tolerance was excellent. In one case of renal failure that was reported after angiography, the patient had received both iodine and gadolinum-based contrast agents. CONCLUSION: Gadolinium appears to be an interesting alternative for arteriography in patients with absolute or relative contraindication to iodinated contrast agents, and also seems to demonstrate efficacy during endovascular therapeutic procedures.

[Protocol of cleft lip and palate by Saint-Vincent-de-Paul team]. / Fentes labiales et palatines: la prise en charge de l'équipe de Saint-Vincent-de-Paul.

The treatment of cleft lip and palate at Saint-Vincent-de-Paul hospital is realized by a multidisciplinary team. The calendar of the primary treatment is adapted according to the eventual antenatal diagnosis: it may be early and in two sessions, or late at 4 months but in one session. The calendar of the secondary treatment is more classical.

Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria.

Human mature erythrocytes have been considered as unable to undergo programmed cell death (PCD), due to their lack of mitochondria, nucleus and other organelles, and to the finding that they survive two conditions that induce PCD in vitro in all human nucleated cells, treatment with staurosporine and serum deprivation. Here we report that mature erythrocytes can undergo a rapid self-destruction process sharing several features with apoptosis, including cell shrinkage, plasma membrane microvesiculation, phosphatidylserine externalization, and leading to erythrocyte disintegration, or, in the presence of macrophages, to macrophage ingestion of dying erythrocytes. This regulated form of PCD was induced by Ca(2+) influx, and prevented by cysteine protease inhibitors that allowed erythrocyte survival in vitro and in vivo. The cysteine proteinases involved seem not to be caspases, since (i) proforms of caspase 3, while present in erythrocytes, were not activated during erythrocyte death; (ii) cytochrome c, a critical component of the apoptosome, was lacking; and (iii) cell-free assays did not detect activated effectors of nuclear apoptosis in dying erythrocytes. Our findings provide the first identification that a death program can operate in the absence of mitochondria. They indicate that mature erythrocytes share with all other mammalian cell types the capacity to self-destruct in response to environmental signals, and imply that erythrocyte survival may be modulated by therapeutic intervention.

Improved storage of erythrocytes by prior leukodepletion: flow cytometric evaluation of stored erythrocytes.

In vivo phagocytosis of senescent red blood cells (RBCs) by macrophages occurs 120 days after their release into the circulation. It depends on two sequential signals that trigger phagocytosis: (1) desialylation of membrane glycoconjugates with the exposure of the penultimate beta-galactosyl residues and (2) exposure of phosphatidylserine in the membrane outer leaflet. Leukodepleted and nonleukodepleted RBCs were compared using flow cytometric procedures to determine whether the in vitro deterioration of RBCs during storage might be attributable to an identical mechanism of desialylation induced by leukocyte neuraminidases, resulting in exposure of beta-galactosyl and subsequently phosphatidylserine residues - signals of senescent RBCs. Without prior leukodepletion, stored RBCs showed an increased population of senescent RBCs (using light scatter measurements), extensive desialylation with the exposure of beta-galactosyl residues (using specific fluorescein isothiocyanate [FITC]-lectins), significant exposure of phosphatidylserine in the outer leaflet of the RBC membrane (using FITC-annexin V), and extensive in vitro phagocytosis (using PKH-26-labeled RBCs). There were minimal changes observed with the leukodepleted RBCs. These results lead to the conclusion that leukocyte enzymes, including neuraminidases, are definitive contributers to the desialylation of RBCs during storage and to the exposure of phosphatidylserine residues. These deleterious effects resulting from highly active leukocyte enzymes are preventable by prior leukodepletion of the stored RBCs. Previously developed flow cytometric procedures to detect in vivo "RBC senescence" have been applied and proved to be reliable criteria to monitor the viability of stored RBCs.

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). CONCLUSION: Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.

[Blood donation. Job description of the function of a physicion in a district subdivision]. / Don du sang. Fiche de définition de fonction d'un médecin d'arrondissement de collecte.

Following the 1995 national reorganization of the transfusion system, the Nord Pas de Calais blood transfusion center has modified its blood collection organization, with the creation of four districts divided into three or four subdivisions. This change was part of Quality Assurance implementation in the center. This article provides the job description for a physician in charge of such a subdivision as well as the method chosen to design this description (inspired by the diagram of Hijman). This job was conceived as an association of human skills knowledge with the strategy of the blood center. In addition to his medical activity, the district subdivision physician becomes a manager and an organizer. The method used highlights the participation of all disciplines involved in blood donation.

Plateletpheresis concentrates produced with the COMTEC cell separator: the French experience.

The latest generation of cell separators such as Trima (Gambro), Amicus (Baxter) and AS-TEC 204 (Fresenius), allow the collection of leucocyte-reduced platelet concentrates without secondary filtration. Fresenius has recently developed the COMTEC cell separator whose performance has been evaluated by several teams in France. This new cell separator is an improved version of the Fresenius AS-TEC 204 cell separator, designed to allow more efficient platelet collections. This study reports on the experience of six French teams (from Bordeaux, Clermont-Ferrand, Creteil, Dijon, Lille and Nancy) who obtained 696 leucocyte-reduced plateletpheresis concentrates in the course of collection using the new Fresenius COMTEC cell separator. All healthy volunteer donors fulfilled French selection criteria for platelet apheresis. Donors were eligible if they had suitable venous accesses, if their bodyweight was *50 kg and if their pre-apheresis platelet count was >150 x 10(9) l(-1). Between 4606 and 5229 ml of blood were processed. The mean volume of the platelet concentrates was between 439 and 493 ml (mean 460 +/- 63 ml). The platelet yield was of the order of 5.18 +/- 1.02 x 10(11) with only one platelet concentrate below the norm of 2 x 10(11) platelets (0.91 x 10(11)). No plausible explanation for this was found. The residual leucocyte levels conform to current norms. The platelet concentrates contained less than 1 x 10(6) leucocytes per concentrate (mean 0.233 +/- 0.150 x 10(6) leucocytes) in more than 97% of the components produced with >95% statistical confidence. The efficacy of the cell separator (52.44 +/- 7.35%) is comparable to that of other separators. The Fresenius COMTEC cell separator makes it possible to obtain leucocyte-reduced platelet concentrates which comply with current standards both in terms of platelet content and residual leucocyte level.

Linac radiosurgery for cerebral arteriovenous malformations: results in 169 patients.

PURPOSE: To present the SALT group results using Linac radiosurgery (RS) for AVM in 169 evaluable patients treated from January 1990 thru December 1993. METHODS AND MATERIALS: Median age was 33 years (range 6-68 years). Irradiation was the only treatment in 55% patients. Other treatment modalities had been used prior to RS in 45%: one or more embolizations in 36%, surgery in 6%, and embolization and surgery in 3% patients. Nidus were supratentorial in 94% patients, infratentorial in 6% patients. Circular 15 MV x-ray minibeams (6-20 mm) were delivered in coronal arcs by a GE-CGR Saturne 43 Linac. Patient set-up included a Betti arm-chair, a Talairach frame. Prescribed peripheral dose was 25 Gy on the 60%-70% isodose (max dose 100%). Arteriographic results were reassessed in December 1997 at 48 to 96 months follow-up. RESULTS: The overall obliteration rate (OR) was 64% (108/169). AVM volumes ranged from 280 to 19,920 mm(3), median 2460 mm(3). OR was 70% for AVM

[Bacterial contamination of platelet concentrates by Propionibacterium acnes]. / Contamination bactérienne de concentrés de plaquettes à Propionibacterium acnes.

In this study, three incidents of platelet contamination by Proprionibacterium acnes and an investigation of the transfusion process have been reported, which occurred at the Nord-Pas-de-Calais Blood Center over a period of several months. P. acnes is a bacterium that is present in the cutaneous flora; it does not produce any toxin, and is rarely considered as a pathogenic agent; its occurrence is widespread, in particular in those regions that are rich in sebum (face, back, scalp), and it is extremely apparent during adolescence. The three incidents occurred following the transfusion of a pool of leucodepleted platelet concentrates obtained from immunodeficient patients. The clinical outcome was in all cases positive. It was considered that the bacterial contamination of platelet concentrates could reflect insufficient skin disinfection at the site of the venipuncture and a minimal bacterial risk involving the blood collection procedure.