[Reprint of: Severe pre-eclampsia: guidelines for clinical practice from the French Society of anesthesiology and intensive care (SFAR) and the French College of gynaecologists and obstetricians (CNGOF)]. / Republication de : recommandations formalisées d'experts. Prise en charge de la patiente avec une pré-éclampsie sévère­RFE communes Société française d'anesthésie-réanimation (SFAR)­Collège national des gynécologues et obstétriciens français (CGNOF).

OBJECTIVE: To provide national guidelines for the management of women with severe preeclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict of interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasized. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe preeclampsia was published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analyzed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1±), 9 have a moderate level of evidence (GRADE 2±), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe preeclampsia.

[Maternal mortality due to cardiovascular disease in France 2013-2015]. / Mortalité maternelle par maladies cardiovasculaires en France 2013­2015.

Between 2013 and 2015, cardiovascular diseases became one of the two leading causes of maternal mortality, with 36 deaths (13.7% of maternal deaths). The overall maternal mortality ratio for cardiovascular diseases is 1.5 per 100,000 live births, stable compared to the 2010-2012 period. The etiologies in order of decreasing frequency are: pre-existing cardiomyopathies (n=10), aortic dissections (n=9), peripartum cardiomyopathies (n=6), myocardial infarction (n=4), valvular cardiopathies (n=4). Non-optimal care occurred in 72% of cases, increasing since the previous triennium (50%). Similarly, there is a significant increase in the proportion of preventable deaths (possibly or probably) from 35% to 66%. In women with known cardiovascular disease, the lack of multidisciplinary prepregnancy assessment and pregnancy follow-up is most frequent. In patients with unknown cardiovascular disease, the lack of diagnosis of a cardiac event is the most common failure. Cardiovascular conditions or cardiovascular risk factors should be investigated in early pregnancy in order to monitor and refer women to appropriate maternity hospitals. Recent dyspnea, worsening at the end of pregnancy and postpartum, should suggest a cardiac complication. In presence of chest pain, aortic dissection should be considered with the same degree of emergency as myocardial infarction or pulmonary embolism. Cardiac ultrasonography, chest CT, Nt-proBNP and troponin should be considered in case of chest pain or recent dyspnea. Women with cardiac symptoms should be referred to an emergency department (not necessarily to the local maternity) for a complete cardiovascular check-up.

Stromal factors support the expansion of the whole hemopoietic spectrum from bone marrow CD34+DR- cells and of some hemopoietic subsets from CD34+ and CD34+DR+ cells.

Ex vivo expanded bone marrow CD34+DR- cells could offer a graft devoid of malignant cells able to promptly reconstitute hemopoiesis after transplant. We investigated the specific expansion requirements of this subpopulation compared to the more mature CD34+ and CD34+DR+ populations. The role of stromal factors was assessed by comparing the expansion obtained when the cells were cultured in (1) long-term bone marrow culture (LTBMC) medium conditioned by an irradiated human BM stroma (CM), (2) medium supplemented with 15% FBS (FBSM) and (3) non-conditioned LTBMC medium (LTM) for 21 days. The effect of the addition of G-CSF (G) and/or of MIP-1alpha (M) to a combination of IL-3, SCF, IL-6 and IL-11 (3, S, 6, 11) was analyzed. Compared to CD34+DR- cells, CD34+ and CD34+DR+ cells gave rise to a similar number of viable cells and to a lower progenitor expansion. The expansion potential of CD34+ and CD34+DR+ cells was equivalent in CM and in FBSM except for both the emergence of CD61 + megakaryocytic cells and LTC-IC maintenance which were improved by culture in CM. In contrast, expansion from CD34+DR- cells was enhanced by CM for all the parameters tested. Compared to FBSM, CM induced a higher level of CFU-GM and BFU-E expansion and allowed the emergence of CD61+ cells. HPP-CFC were maintained or expanded in CM but decreased in FBSM. Compared to input, the number of LTC-IC remaining after 21 days of CD34+DR- expansion culture was strongly decreased in FBSM and variably maintained or expanded in CM. Comparison with LTM indicated that stroma conditioning is responsible for this effect. G-CSF significantly improved CFU-GM and HPP-CFC expansion from CD34+DR- cells without being detrimental to the LTC-IC pool. The growth of CD61+ cells was significantly enhanced by G-CSF in CM. Addition of MIP-1alpha had no significant effect either on progenitor expansion or on LTC-IC, regardless of culture medium. We conclude that factors present in stroma- conditioned medium are necessary to support the expansion of the whole spectrum of hematopoietic cells from CD34+DR- cells and to support the expansion of cell subsets from CD34+ and CD34+DR+.

Atypical lymphocytic leukemia and mantle cell lymphoma immunologically very close: flow cytometric distinction by the use of CD20 and CD54 expression.

Integration of morphological and immunophenotypic data is critical in achieving diagnosis accuracy and minimising interobserver interpretative discrepancies. The aim of this work was to compare the immunophenotype and the morphology of chronic lymphocytic leukaemia and mantle cell lymphoma, to help in the differential diagnosis of CD5 positive monoclonal B cells. Frozen/thawed samples from 91 patients were analysed retrospectively. Fresh samples from 17 mixed/atypical CLL and 13 MCL were tested to corroborate the results. Markers were analysed as percentage (%) of positive B lymphocyte subpopulation, and in terms of median fluorescence intensity (MFI). Matutes's CLL score clearly allowed distinguishing between classical CLL on the one hand, and atypical CLL and MCL on the other hand. The percentage of CD54-positive cells and the median fluorescence intensity of CD20 and CD54 were the only parameters which were significantly higher in MCL than in atypical CLL (P < 0.05), allowing an immunological distinction between these two entities. Nevertheless, due to a quenching problem when using CD20 and CD54 together, and because CD18 showed a statistically different expression between classical and atypical CLL, the combination of CD18/CD54 has been preferred and showed a different pattern in the three entities. Immunophenotyping could be helpful in the differential diagnosis of CD5-positive B cell chronic lymphoproliferative disorders with atypical features that do not fit exactly into any of the morphologic proposed groups.

[Management of placenta percreta]. / Prise en charge des placentas percreta.

Placenta percreta is a severe condition associated with maternal morbidity and mortality even when surgery is performed electively. Arteries ligation, embolisation, medical treatment by methotrexate can be appropriate treatment to avoid catastrophic surgery. The purpose of this report is to present a case where the placenta was left in situ to avoid cystectomy at the time of cesarean section, with subsequent failure of the conservative treatment.

[Alternative techniques to labour epidural analgesia]. / Alternatives à l'analgésie péridurale au cours du travail.

Many systemic techniques, so-called "alternatives" to labor epidural analgesia, have been described: they are all poorly effective and some are associated with significant maternal and neonatal side effects. Nonetheless, these techniques can provide good maternal satisfaction. Accordingly, they are indicated when epidural analgesia is contraindicated or unavailable. Administration of systemic opioids mandates maternal respiratory supervision, oxygen supplementation and/or pulse oxymetry. Systemic opioids may also decrease fetal heart rate variability and produce neonatal respiratory depression; naloxone administration to the neonate is therefore widely indicated. Pethidine should be abandoned because it can produce prolonged neonatal respiratory depression. Nalbuphine produces less nausea/vomiting and less long lasting neonatal respiratory depression. Intravenous PCA fentanyl or sufentanil is presently the method of choice during early labor. Alfentanil seems less effective and may produce more neonatal side effects. Intravenous PCA remifentanil is the most effective technique, but safe administration may be problematic during intermittent supervision usually implemented in labour ward. Nitrous oxide 50% provides little pain relief. Nonetheless, it is associated with few side effects, quite good maternal satisfaction and can be quickly implemented during advanced painful labor. It is not recommended to add it to systemic opioid (except under continuous supervision by the anaesthetic team), because of an increased incidence of maternal desaturation. The use of a subanaesthetic concentration of sevoflurane has been described recently; it is more effective than nitrous oxide. However, guidelines for safe implementation in labor ward remain to be determined.

Improved IL-2 detection for determination of helper T lymphocyte precursor frequency in limiting dilution assay.

In the context of allogeneic bone marrow transplantation, an accurate estimate of the risk of developing graft-versus-host disease (GVHD) is of major interest. The pre-transplant frequency of donor's helper T-lymphocyte precursors (HTLp) directed against host's antigens may be helpful in predicting this risk. This technique relies on an indirect measurement of interleukin-2 (IL-2) secreted by the HTLp, as assessed by the proliferation of an IL-2 dependent cell line. Many authors use the murine CTLL-2 cell line in this assay, but these cells do not respond to the presence of minute amounts of IL-2 in the culture medium, and thus do not discriminate between the absence or the presence of very low levels of IL-2. We therefore decided to compare CTLL-2 with another IL-2 dependent cell line, the murine A9.12 cell line. A comparison was made using serial dilutions of recombinant human IL-2, limiting dilutions of baby hamster kidney (BHK) cells transfected with human IL-2 gene and in the context of clinical tests performed for the detection of pre-transplant HTLp. Both the sensitivity and reliability of the tests were better using A9.12. We conclude that the A9.12 cell line might be a more suitable tool for pre-transplant HTLp determinations before allogeneic bone marrow transplantation or whenever low IL-2 levels are to be measured.

Reference values for peripheral blood B-lymphocyte subpopulations: a basis for multiparametric immunophenotyping of abnormal lymphocytes.

BACKGROUND AND OBJECTIVES: Immunophenotyping has become a useful tool for the differential diagnosis of chronic B-cell lymphoproliferative disorders. The aim of this work was to determine reference values of normal B-cell subpopulations. MATERIAL AND METHODS: Blood samples from 38 healthy volunteers were analyzed by multidimensional flow cytometry, using a panel of directly conjugated antibodies. Results were expressed as percent of positive B cells and as median fluorescence intensity, an indirect assessment of the expression level. RESULTS: CD20, CD22, CD24, CD40, CD79a, CD79b, FMC7, CD11a, CD18, CD44 were positive in the whole B cell population, whereas CD10, CD86, CD103, CD154 and FasL were almost absent from the B-lymphocyte population. 75% were IgD positive. The kappa/lambda ratio was 1.5. CD5, CD23, CD25, CD38, CD43, CD54, CD62L, CD80 and CD95 were positive in different B-cell subpopulations. The utility of all these markers in the differential diagnosis of chronic B-cell lymphoproliferative disorders is discussed. CONCLUSION: In order to interpret a pathological immunophenotype, it is necessary to refer to quantitative and qualitative values of normal B-cell subpopulations.

Impact of cryopreservation on B cell chronic lymphocytic leukaemia phenotype.

BACKGROUND AND OBJECTIVES: Freezing is a practical approach for cell preservation for retrospective studies. The aim of this work was to check the cryopreservation impact on B cell chronic lymphocytic leukaemia phenotype. MATERIAL AND METHODS: Blood samples from 15 CLL patients were analyzed freshly and after freezing at -196 degrees C, without separation, and thawing. Results were compared by Student's paired t-test. RESULTS: The phenotype of fresh CLL cells was as follows: CD19+, CD5+, faint CD20, CD23+/-, weak CD22 and sIg, CD37+, HLA-DR+, FMC7-. After cryopreservation, the percentage of CD5 and CD23 positive cells decreased, whereas HLA-DR positive cells increased moderately. The CLL Matutes's score was modified in 6 cases out of 15 (40%). CONCLUSION: Cryopreservation modifies B cell chronic lymphocytic leukaemia phenotype, by decreasing CD5 and CD23 expression.

The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients.

It is widely believed that multiple sclerosis is a T-cell mediated autoimmune disease associated with abnormalities in immunoregulation. This large, prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS patients, divided clinically into a remitting/relapsing group (n = 176) and a progressive group (n = 70), and compared their results to those of 117 healthy controls. All patients were found to have significantly elevated percentage and absolute numbers of IL2R+CD3+ cells as well as depressed percentages of CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide (CY) versus no treatment or treatment with other agents was used to group patients, dramatic declines in both percentages and absolute numbers of CD45RA+CD4+ cells were discovered. These declines were associated specifically with CY and and could be explained by this factor independent of the clinical state of the patient. The effects were seen in patients undergoing current treatment or in those exposed to CY in the near or remote past. These findings highlight the confounding effect of specific treatments on the immune profile of MS patients groups and suggest that there may be important implications for cellular function and clinical outcome in these and other patient groups.

Intracellular cytokine profile of cord and adult blood monocytes.

Cord blood (CB) transplantations are associated with low graft-versus-host disease (GVHD). The pathophysiology of GVHD involves interaction and activation of different cell types, as lymphocytes and monocytes, and results in a cascade of cytokine production. After antigen or mitogen stimulation, CB monocytes release lower levels of cytokines than adult blood (AB) monocytes. In this study, the detection of intracellular IL-1 beta and TNF-alpha produced by monocytes was evaluated in response to tuberculin PPD to investigate whether the reduced capacity of CB monocytes to secrete cytokines could be related to an impaired functional activity and to a particular phenotypic profile. Results showed that the percentage of CD64(+)monocytes producing intracellular IL-1 beta and TNF-alpha was significantly lower in CB and that the phenotypic profile of CB monocytes producing these cytokine (CD64(+)CD14(+)) was different to that of AB monocytes (CD64(+)CD14(+), CD64(+)CD33(+) and CD64(+) CD45RO(+)). These results suggest that the lower capacity of CB monocyte populations to produce IL-1 beta and TNF-alpha might be due to a functional immaturity of CB monocytes at the cellular level as reflected by the different phenotypic profile of CB monocytes.

Bone marrow transplantation from an unrelated donor for Fanconi's anaemia: two unusual complications.

An eight-year-old boy with Fanconi's anaemia received a bone marrow transplantation from an unrelated donor. Sustained engraftment was achieved, but he developed major complications including acute grade III graft-versus-host disease, autoimmune haemolytic anaemia with positive Coombs' test and free antibodies against Rhesus group, and a virus-associated haemophagocytic syndrome; this latter complication was successfully treated with acyclovir. Sixteen months after transplantation he has full haematopoietic reconstitution, but with persisting mild autoimmune haemolysis.

Allogeneic or autologous bone marrow transplantation for acute non-lymphocytic leukemia in first remission.

One hundred and seven consecutive patients with acute non-lymphocytic leukemia (ANL) aged less than 56 years were allocated to receive either allogeneic (allo-BMT) or autologous bone marrow transplantation (auto-BMT) when first complete remission (CR1) was achieved. CR was obtained in 96 patients. Twenty-four patients had an HLA-identical sibling donor and 20 of these (83%) had an allograft in CR1. Thirty-three patients (44% of the CR1 patients without donor) had an autograft in CR1. The reasons for not transplanting patients in CR1 were early relapse (nine patients), refusal (11 patients) or medical problems (23 patients). The 4-year leukemia-free survival (LFS) probability for all the CR1 patients was 25%. For the allo-BMT patients, the 4-year LFS was 71%, and for the auto-BMT patients 31% (log-rank p = 0.028). The relapse probabilities were 33% and 48% respectively (p = 0.40). If the results are analysed according to the intent of the protocol, patients with a donor had an LFS of 53%, and patients without a donor an LFS of 16% (p = 0.003). This study confirms the value of allo-BMT for consolidation of ANL in CR1. The attempt to autograft all CR1 patients without a compatible donor has not resulted in any marked improvement of LFS.

Long-term culture of autologous transplanted bone marrow for acute myeloid leukaemia: evidence for an in vitro haemopoietic defect and lack of correlation with the speed of engraftment.

Haematological recovery after autologous bone marrow transplantation (BMT) for acute myeloid leukaemia (AML) is often delayed and available laboratory assays cannot accurately predict speed of engraftment. By using the long-term bone marrow culture (LTBMC) method, we attempted to define the haemopoietic defect underlying this slow engraftment, and assessed the usefulness of LTBMC in predicting engraftment. Cryopreserved bone marrow (BM) harvested from three different groups (AML autografts, n = 18; autografts for non-leukaemic diseases, n = 23; normal donors. n = 10) were cultured and their growth was compared and correlated with the speed of engraftment. In the AML autografts, non-adherent and adherent progenitor production was significantly reduced compared with normal BM during the whole culture period (P < 0.01). None of the LTBMC parameters was found to correlate with engraftment after autologous BMT. The non-leukaemic autografts showed progenitor production intermediate between normal and AML autografts. Their progenitor content at the end of the culture period (reflecting the stem cell pool) was not statistically different from normal BM. In this group, most of the progenitor cell contents, during LTBMC correlated with neutrophil (rs = -0.618 to -0.879, P < 0.01) and platelet (rs = -0.479 to -0.707, P < 0.02) recovery. The conclusion drawn from these results is that AML autografts are defective in their ability to sustain in vitro haemopoiesis, but this in vivo defect does not correlate with the slow haemopoietic recovery after autologous BMT. In contrast, LTBMC of autografts for non-leukaemic diseases, whose defect affects the stem cell pool to a lesser extent than BM in AML correlates with the speed of engraftment.

Circadian and seasonal variations of hematopoiesis in cord blood.

Cord blood hematopoietic progenitors undergo circadian and seasonal variations. The lowest values are obtained between 4:00 and 12:00, as well as between May and August. This represents the first observation of such rhythms before birth.

HLA antigens and progression of multiple sclerosis. Part II.

The HLA-A, -B, -C and -D were determined in 200 multiple sclerosis (MS) patients, 64 of whom underwent a CSF examination. Their frequencies were correlated with the rate of disease progression and with factors thought to influence disease progression, including onset age, type of clinical course and intrathecal IgG synthesis. No correlation was found between HLA haplotypes and progression rate or type of disease course. Patients starting MS after age 31 years carried the DR2 determinant more frequently (P = 0.016) than patients with onset before this median age. Although the greatest proportion of patients with an IgG index greater than 1.5 or more than 15 oligoclonal bands in their CSF were DR2 carriers, no statistical difference was found in the intrathecal IgG synthesis of HLA-DR2 (+) and (-) patients.

Breakpoints of 11q25 in three similar cases of B non Hodgkin's lymphoma.

We report three cases of small B cell non Hodgkins lymphoma, two with plasmacytoid differentiation, presenting with a similar clinical picture and identical immunophenotype, who cytogenetically had breakpoints involving band 11q25. We suggest that this breakpoint may define a group of lymphomas closely related to the diffuse small cleaved cell lymphomas with t(11;14)(q13;q32).

Increased "in vivo" lymphocyte blastogenesis in the peripheral blood of patients with atopic dermatitis and allergic contact dermatitis.

The spontaneous 3H-thymidine (3HT) labelling of some lymphocyte subpopulations has been studied in the peripheral blood of five patients with atopic dermatitis and five with widespread allergic contact dermatitis and compared with that in 10 healthy subjects. One hour after addition of 3HT to heparinized blood, lymphocytes were separated and processed with two different rosetting techniques (E-rosette test and Active E-rosette test). The cell suspensions were cytocentrifugated and autoradiography undertaken. An increased number of 3HT labelled lymphocytes was observed in the peripheral blood of patients with dermatitis as compared to controls. These labelled lymphocytes were E-rosette-forming cells (T cells) and E-non-rosette-forming cells (non-rosette-forming T cells and non-T cells). The ratio between the labelling index (LI) of E-rosette- to the LI of non-E-rosette-forming cells was in favour of T cells in allergic contact dermatitis (ratio = 3.09) whereas in atopic dermatitis (ratio = 0.93) the DNA synthesis was relatively greater in the non-rosette-forming cells. It is suggested that this increased LI of peripheral blood lymphocytes could be related to the increased derman mononuclear cell 3HT-labelling that has been reported previously in these inflammatory skin diseases.

Neuromuscular disorders associated with D-penicillamine treatment for rheumatoid arthritis.

Three cases of D-penicillamine (DPA) induced myasthenia gravis (MG) and one case of DPA-induced polymyositis (PM) are reported among four patients suffering from seropositive rheumatoid arthritis. The cumulative doses responsible for the three DPA-induced MG cases amounted respectively to 73, 117 and 467 g. The cumulative dose responsible for the DPA-induced PM case amounted to 465 g. All the patients were HLA DR1. All four cases healed completely after withdrawal of DPA. The aetiology of the cases is discussed and the literature is reviewed. These cases represent further instances of DPA-induced neuromuscular disorders.

The SANGUIS Study in Belgium: an overview of methods and results. Safe and good use of blood in surgery.

SANGUIS was multicentric European study involving more than 7,000 patients in 43 teaching hospitals during a one year period. The goal of the study was to describe current transfusion practice for elective surgery in adult. The present paper summarizes the data collected on the 1,193 patients enrolled in Belgium. It also introduces the final report of the SANGUIS study in Belgium, which will be published as a special issue of the Acta Chirurgica Belgica.