[Analysis of causes of destruction of labile blood products in health institutions: A multicentric study]. / Analyse des causes de destruction des produits sanguins labiles dans les établissements de santé : une étude multicentrique.

OBJECTIVE: One of the tasks of haemovigilance correspondents in Health Institutions (HI) is to reduce the destruction of labile blood components (LBC). The objective of this study was to analyse in depth, five years after a first multicentric study, the causes of LBC destruction in order to assess the impact of measures taken and to define new ways of improvement. METHODS: Prospective analysis was carried out throughout 2016. For every LBC destroyed, the following elements were reported: type of LBC, transfusion department, cause of destruction analysed according to a decision tree, subsequently classed as avoidable or unavoidable. RESULTS: The study included 15 HI. A total 3058 LBC were destroyed, representing an average 0.90% of issued LBC, and this analysis concerned 2576 LBC. Sixty-seven percent of LBC were issued for surgery, intensive care or emergencies. Forty percent of the causes of destruction were patient-related (death, clinical worsening, adverse effects or abnormal constants prior to delivery). Thirty percent were prescription-related, mainly cases of excessive prescription for different reasons. Eleven percent were linked to organisational issues. The rate of destruction judged avoidable, all causes combined, was 36%. CONCLUSION: Comparison with the precedent study shows improvement, thus revealing the efficacy of implemented measures (single-dose distribution, return procedures back to the site of distribution, training of participants). In order to further reduce this rate of destruction, we suggest to promote storage procedures and, above all, to continue to raise awareness within healthcare teams.

[Is the research of posttransfusional alloantibodies still relevant?] / Est-ce que la réalisation de la recherche d'anticorps antiérythrocytaires post­transfusionnelle est toujours pertinente ?

The decision of November 6th, 2006 defining the principles of best practices recommends that posttransfusional red cell alloantibodies research is performed after one to three months after. In the University hospital of Brest, the haemovigilance unit takes charge of sending the medical prescription within the required time and centralizing the results. We wished to estimate if the realization of this research still remains relevant. METHODS: A prospective analysis was performed in 2015. We evaluated the realization rate, the red cell alloantibodies rate and the recipient adverse reactions with the diagnostic category: alloimmunization (delayed serological transfusion reaction, DSTR). RESULTS: In 2015, 2162 prescriptions were sent to the 3271 transfused patients. One thousand and eighteen red cell alloantibodies research were done, i.e. a return rate of 61%. Among them, 12 alloantibodies appeared (0.9%) within an average of 56 days. Thirty-three other alloantibodies appeared and were discovered most frequently before a new transfusion. In 10 cases, a posttransfusional research was done that was negative. A survey was conducted among GHCOH members to describe the practices in these health institutions. Twelve questionnaires were analysed. Ten institutions performed a posttransfusional alloantibodies research by issuing a prescription at the patient's exit with a return rate between 0.14 and 16%; 1 institution has a centralized organization with a return rate of 68.3%; 1566 red cell alloantibodies research were performed and among them, 24 alloantibodies appeared (1.53%). CONCLUSION: These results indicate that to be effective, the management of this biological test must be centralized. Despite this, the red cell alloantibodies rate remains very low (0.9 and 1.53%) and raises the question of the relevance of this systematic testing after transfusion, which is in any case mandatory before a new transfusion of red blood cells.

Long-term neurologic and cardiac correction by intrathecal gene therapy in Pompe disease.

Pompe disease is a lysosomal storage disorder caused by acid-α-glucosidase (GAA) deficiency, leading to glycogen storage. The disease manifests as a fatal cardiomyopathy in infantile form. Enzyme replacement therapy (ERT) has recently prolonged the lifespan of these patients, revealing a new natural history. The neurologic phenotype and the persistence of selective muscular weakness in some patients could be attributed to the central nervous system (CNS) storage uncorrected by ERT. GAA-KO 6neo/6neo mice were treated with a single intrathecal administration of adeno-associated recombinant vector (AAV) mediated gene transfer of human GAA at 1 month and their neurologic, neuromuscular, and cardiac function was assessed for 1 year. We demonstrate a significant functional neurologic correction in treated animals from 4 months onward, a neuromuscular improvement from 9 months onward, and a correction of the hypertrophic cardiomyopathy at 12 months. The regions most affected by the disease i.e. the brainstem, spinal cord, and the left cardiac ventricular wall all show enzymatic, biochemical and histological correction. Muscle glycogen storage is not affected by the treatment, thus suggesting that the restoration of muscle functionality is directly related to the CNS correction. This unprecedented global and long-term CNS and cardiac cure offer new perspectives for the management of patients.

Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy.

Sepsis, or systemic inflammatory response syndrome, is the major cause of critical illness resulting in admission to intensive care units. Sepsis is caused by severe infection and is associated with mortality in 60% of cases. Morbidity due to sepsis is complicated by neuromyopathy, and patients face long-term disability due to muscle weakness, energetic dysfunction, proteolysis and muscle wasting. These processes are triggered by pro-inflammatory cytokines and metabolic imbalances and are aggravated by malnutrition and drugs. Skeletal muscle regeneration depends on stem (satellite) cells. Herein we show that mitochondrial and metabolic alterations underlie the sepsis-induced long-term impairment of satellite cells and lead to inefficient muscle regeneration. Engrafting mesenchymal stem cells improves the septic status by decreasing cytokine levels, restoring mitochondrial and metabolic function in satellite cells, and improving muscle strength. These findings indicate that sepsis affects quiescent muscle stem cells and that mesenchymal stem cells might act as a preventive therapeutic approach for sepsis-related morbidity.

[Hospital haemovigilance and adverse events or reactions: who notifies and what?]. / Gestion des évènements indésirables receveurs: le point de vue de l'hémovigilant d'un établissement de santé.

The French haemovigilance system designates a physician in charge of haemovigilance in each hospital. She/he collects the adverse reactions and events reported by medical staff or nurses. In 2010, 7360 (2.42/1000 units) adverse reactions and 518 adverse events (excepted donors) were reported. These results mean that the system is particularly effective in hospitals. This study collected the opinion of physicians in charge of haemovigilance about this organization.

[Suitability of red blood cell transfusion: a multicenter study]. / Évaluation multicentrique de la pertinence des prescriptions de concentrés de globules rouges.

The purpose of this retrospective observational multicenter study was to assess appropriateness of red blood cell (RBC) transfusion, according to the French national guidelines (Agence française de sécurité sanitaire des produits de santé) published in 2002. Six hundred and thirty-nine RBC transfusions from nine institutions have been randomly selected and analysed. The data collected are issued from different specialities. Patients' characteristics, occurrences of transfusion, admission, pre-transfusion, post-transfusion and discharge haemoglobin concentrations have been collected. Two physicians (who are in charge) must evaluate the appropriateness of pre-transfusion, discharged haemoglobin concentrations, quantity and quality of transfused RBC. The mean pre-transfusion haemoglobin concentration was 7.89 ± 1.24, the median number of transfused RBC was two (extremes: 1-16), the mean discharge haemoglobin concentration was 10.14 ± 1.30 (-5 days after the end of transfusion). The pre-transfusion and discharge haemoglobin concentrations were higher if the patient presented a co-morbidity factor. Ninety-three percent of pre-transfusion and 79% of discharge haemoglobin concentrations are in accordance with the guidelines. According to the physicians, the RBC transfusions are too "precocious" when pre-transfusion haemoglobin concentration is above nine and the anaemia is asymptomatic. 50% of RBC transfusion with discharge haemoglobin concentration above 10 is not excessive. In case of acute anaemia, the pre-transfusion and discharge haemoglobin concentrations are higher and RBC transfusion excessive. In this study, the trigger haemoglobin concentration is "restrictive", but the target haemoglobin concentration is "liberal" with a high-discharge haemoglobin concentration. Inappropriate RBC transfusions are mainly due to over-transfusion.

[Assessment of knowledge in blood transfusion of medical staff in 14 state-run hospitals]. / Evaluation des connaissances médicales transfusionnelles dans 14 établissements publics de santé

UNLABELLED: This multi-centre study aimed to assess the knowledge in blood transfusion of medical staff in 14 state-run hospitals. MATERIALS AND METHODS: A questionnaire was distributed to all potential prescribers of blood products. It contained 35 questions concerning various subjects: blood products, immuno-haematology, prescription of blood products, transfusion practice, interpretation of the final bedside controls. The rate of correct answers (RCA) was obtained for each question, for each subject, and for nine questions defined as essential for patient safety. A weighted score was also calculated by ranking each question between one and six according to its importance. RESULTS: Six hundred and ninety four questionnaires were analysed (rate of return 15%). The RCA ranged from 14 to 89%, according to the questions. The RCA ranged from 47 to 78% for seven of the nine essential safety questions, and 82% and 83% for the two questions concerning the interpretation of incompatible final bedside controls: there were 9% of wrong answers, which validated an incompatible blood transfusion. The mean weighted score was 62%. Both the RCA and the weighted score were higher for those that regularly prescribe blood products than for that only prescribe them occasionally. There were no significant differences between hospitals. CONCLUSION: This study has confirmed that medical staff have deficiencies in their knowledge of blood transfusion, deficiencies which are acknowledged by medical staff. These first results will help the members of the study group to develop and prioritize various actions to improve this state of affairs, and to follow the effects of the training given.

Sarcoplasmic reticulum function in newborn ferret cremaster skeletal muscles.

A study of the properties of the sarcoplasmic reticulum was performed with newborn ferret cremaster muscles at two different development stages: at 8 and 21 days. The effects of extracellular Ca2+, caffeine and cyclopiazonic acid, a specific sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, were examined on intact cremaster skeletal muscles. The uptake and release of Ca2+ were explored on saponin-skinned fibres with or without cyclopiazonic acid and some results obtained were compared with those obtained with adult cremaster muscle. The results have shown that skeletal muscle sarcoplasmic reticulum of newborn animals possesses the ability to accumulate and release Ca2+. Furthermore, application of cyclopiazonic acid modified the twitch, the caffeine responses and decreased the amount of Ca2+ taken up by the sarcoplasmic reticulum in saponin-skinned fibres. In contrast to adult skeletal muscle, in newborn cremaster muscles, the Ca2+ dependence of the twitch suggests that the Ca2+ influx at the sarcolemma level was mainly involved in the activation of the contraction. Furthermore, the results obtained in the presence of cyclopiazonic acid were in favour, as in adult muscle, of a participation of the sarcoplasmic reticulum in the relaxation process.

Effect of cyclopiazonic acid on contractile responses in slow and fast bundles of cremaster skeletal muscle from the ferret.

The effects of cyclopiazonic acid (CPA) on twitch force, calcium (Ca2+) uptake and release by the sarcoplasmic reticulum (SR), and Ca2+ sensitivity of contractile apparatus were studied using intact and chemically skinned cremaster fibers and compared with those on the extensor digitorum longus and soleus. In cremaster muscles treated with CPA (0.5-5 microM) a potentiation of the twitch was observed, associated with an increase in time to peak and in time of relaxation. In Triton-skinned fibers, CPA, at concentrations less than 10 microM, exerted no significant effect on the contractile apparatus of either slow- or fast-twitch fibers. In slow-twitch fibers, a dose-dependent increase in Ca2+ sensitivity was associated with a decrease in maximal tension, at CPA concentrations > 10 microM. In saponin-skinned fibers, during the uptake phase, CPA at > 10 microM induced a dose-dependent decrease in caffeine contracture. The possibility of an action on the SR Ca2+ release channel was excluded by testing the effect of CPA during the releasing phase. The enhancing effect of CPA (0.5-5 microM) on mechanical activity could be explained by an inhibition of the SR Ca2+ ATPase in skeletal muscle cells without an effect on the contractile proteins. Our results strongly suggest that CPA (< 10 microM) has a highly specific effect on the SR Ca2+ pump in the fast- and slow-twitch fibers and therefore could be a good tool to study the mechanisms of Ca2+ regulation in skeletal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cyclopiazonic acid on Ca(2+)-activated tension production in skinned skeletal muscle fibres of the ferret.

The effect of cyclopiazonic acid, an inhibitor of sarcoplasmic reticulum Ca(2+)-ATPase, was investigated on force generation by the contractile apparatus in Triton-skinned fibres from extensor digitorum longus and soleus. Concentrations of cyclopiazonic acid lower than 10 microM were without effect on Ca(2+)-activated tension in both types of muscles. In contrast, in soleus, cyclopiazonic acid (20, 50, 100 microM) was found to shift reversibly the relation-tension pCa (-log[Ca2+]) towards lower free Ca2+ and to decrease maximal Ca(2+)-activated tension, in a dose-dependent manner. In extensor digitorum longus, the Ca2+ sensitivity was significantly increased only at a high cyclopiazonic acid concentration (100 microM) and for all the concentrations tested between 5 to 100 microM maximal Ca(2+)-activated tension was unchanged. These results suggest that cyclopiazonic acid has a direct effect on contractile proteins, in a dose-dependent manner. Ca2+ sensitivity and Ca(2+)-activated maximal tension of the contractile apparatus were differentially affected in fast- (extensor digitorum longus) and slow-twitch (soleus) fibres from ferret skeletal muscle.

Calcium sensitivity of skinned ferret EDL, soleus, and cremaster fibers.

The properties of the contractile system at different times of the year in the ferret extensor digitorum longus (EDL), soleus and cremaster muscles were examined by using chemically skinned (Triton X-100) preparations. The results show clear differences in calcium sensitivity between these skeletal muscles. The apparent calcium threshold for activation was lower in soleus than in EDL, while calcium concentrations ([Ca2+]) required to obtain the half-maximal tension, expressed as pCa50 (-log[Ca2+]), was lower in EDL than in soleus muscle. In fact, pCa50 obtained in fast and slow fibers by fitting the experimental data points by a modified Hill equation was 5.92 +/- 0.02 (n = 9) and 6.09 +/- 0.03 (n = 11) respectively. So EDL appears to be a typical fast-twitch muscle and soleus a typical slow-twitch muscle. Adult ferret cremaster muscle was composed of two types of fibers during the quiescent period similar to EDL and soleus, and only one type that was intermediate between EDL and soleus in the breeding period, as assessed by pCa50 values. These annual modifications in calcium activation of adult ferret cremaster muscle could be related to changes in the function of these muscles and may be correlated with seasonal variations of sexual activity.

Activation of two types of fibres in ferret, Mustela putorius furo, cremaster muscle.

Some contractile, histochemical, morphological and electrophysiological properties of ferret, Mustela putorius furo, cremaster muscle have been estimated. Histochemical fibre typing revealed the presence of two types of fibres (type I 66.2%, type II 33.8%). Morphometry performed on ATPase-stained transverse sections showed that type I was composed of a large amount (40%) of small (less than 1400 microns2) cells. In mammalian Ringer two groups of fibres could be recognized on the basis of the values of resting potential (-69.7 mV and -59.1 mV) intracellular sodium activity (8.3 mmol.l-1 and 14.1 mmol.l-1, respectively). In experiments on fibre bundles, the elevation of extracellular potassium concentration to 15-200 mmol.l-1 produced contractures that consisted of a well-defined transient or phasic tension followed by a sustained or tonic tension. Properties of activation and inactivation of the tension analysed in small bundles of cut fibres (lengths 0.5-1.0 cm) were of fast- and slow-twitch type for phasic and tonic phase, respectively. In contrast to the phasic component of K contractures, the tonic phase was abolished by Ca2+ withdrawal and inhibited by Ni2+, Cd2+, Co2+, Gd3+ and gallopamil (D600). In Ca(2+)-free medium the sustained tension was restored by adding Sr2+. It is concluded that in ferret cremaster muscle the presence of slow-twitch fibres would give rise to the tonic component of the K contracture in which an extracellular source of activator Ca2+ is involved. The ability of these fibres to contract with a maintained tension for prolonged periods of time might participate in the temperature regulation of the testes.

Effects of reduced external sodium concentration and multivalent cations on caffeine contractures in young ferret atrial trabeculae.

The characteristics of caffeine (1.25-80 mM) transient contractures have been examined in small atrial trabeculae (diameters 50-250 microns) isolated from young (1-1.5 months) ferret hearts. In the control medium, the half-saturation constant and the maximum contracture strength (at infinite caffeine concentration) were 37.8 +/- 10.2 mM and 0.9 +/- 0.2 kN.kg-1 (n = 11), respectively. The contractile response to caffeine was markedly enhanced following reduction of external sodium (70-0 mM). The perfusion of young ferret trabeculae with the sodium-free medium (up to 3 min) decreased the half-saturation constant by a factor of three (12.4 +/- 1.6 mM, n = 8) with an increase in maximum contracture strength (1.09 +/- 0.3 kN.kg-1, n = 8). The effects of various divalent and trivalent cations have been tested on the 10 mM caffeine contracture in trabeculae perfused with Na-containing (140 mM) solution. The order of cation effectiveness is Gd3+ (half effect 0.04-0.07 mM) greater than Cd2+ (0.15-0.25 mM) greater than Ni2+ (2-2.5 mM) greater than Co2+ (7-7.5 mM) much greater than Mn2+. In conclusion, the present work has shown that in atrial trabeculae isolated from young ferret hearts, the strength of the caffeine contracture was markedly affected by the activity of the sarcolemmal Na-Ca exchange.

[2 cases of the HELLP (Hemolysis Elevated Liver Low Platelet) syndrome]. / A propos de deux observations de "HELLP (Hemolysis Elevated Liver Low Platelet) syndrome".

Recently described by Weinstein, the "HELLP syndrome" is an entity of the pre-toxemic syndrome; its precise physiopathological mechanism, related to a thrombotic micro-angiopathy, is still not clearly established. Therefore, the treatment remains symptomatic, associated with the treatment of the toxemia. Two cases occurring in twin pregnancies are reported.

[Ante-partum administration of preventive treatment of Rh-D immunization in rhesus-negative women. Parallel evaluation of transplacental passage of fetal blood cells. Results of a multicenter study carried out in the Paris region]. / Application anté-partum du traitement préventif d'immunisation rhésus D chez les femmes rhésus négatif. Evaluation parallèle des passages transplacentaires d'hématies foetales. Résultats d'une étude multicentrique menée en région parisienne.

1,969 non immunized rhesus negative primiparous women were followed up in 23 maternity units in the geographical region of Paris. 1,882 could be retained to study antepartum protection and 1,884 to study transplacental passage of fetal blood cells. Two groups were defined according to whether they were born in even or uneven years, so that: 955 were the "control" group who delivered 590 rhesus D positive infants, and 927 were the "treated" group who delivered 599 rhesus D positive infants. The "control" group were used as controls at the 28th and 34th weeks of pregnancy, while the "treated" group received two injections of anti-D immunoglobulin given on the same dates after taking the necessary tests. Immunological testing at the time of the delivery and after the delivery showed that 7 women had become Rh D immunized in the "control" group whereas only one in the "treated" group. This difference, which is statistically significant, confirms the results of other authors about the efficiency of antepartum rhesus disease prevention. The incidence of immunisation during or immediately after the first pregnancy in women who had no previous story of blood transfusions or of terminations of pregnancy is 1.11%, which is a figure relatively low as compared with studies of series carried out in North America, but close to those carried out in other European centres. When primipara of all categories are lumped together the frequency rises to 1.5%. A study of the passage of fetal red blood cells into the maternal circulation shows that at the 29th week of pregnancy out of 1,884 cases there were 5.5% positive kleihauer tests, without a large volume of blood being detected and at the 34th week of pregnancy when 957 tests were carried out, 7% were positive with one of them being of a massive transfusion of blood from the fetus to the mother, which was life-threatening for the fetus. It may be that the incidence had been under-estimated and that the positive results in the two groups, control and treated, show that there is a statistically significant difference that demonstrates that antepartum treatment in the trial has eliminated a worthwhile percentage of positive kleihauer tests which arose from the transfusion of small quantities of blood.(ABSTRACT TRUNCATED AT 400 WORDS)