Two novel variants of uncertain significance in GP9 associated with Bernard-Soulier syndrome: Are they true mutations?

Bernard-Soulier syndrome (BSS) is an autosomal recessive major thrombocytopathy, the symptoms of which are mainly marked by mucocutaneous bleeding. This rare disease, initially described in the 1970s, is the result of an abnormal formation of the glycoprotein complex Ib-IX-V (GP Ib-IX-V), a platelet receptor of von Willebrand factor. A large number of mutations, sometimes involving the GP9 gene, have been described as possibly responsible for the disease. We report here the case of a BSS patient who presented with persistent thrombocytopenia (31x109/L) and decreased surface expression of GPIb-IX-V on large platelets with anisocytosis. Thorough molecular analyses disclosed two previously unreported GP9 variants, respectively c.230T>A (p.Leu77Gln) and c.255C>A (p.Asn85Lys). Both are likely to modify the conformation of GP-IX interactions with other glycoproteins of the Ib-IX-V complex and thus proper expression of this complex on the membrane of platelets.

[Efficacy and toxicity of short-course corticosteroid therapy in chronic bronchial diseases]. / Efficacité et toxicité de la corticothérapie en cures courtes dans les pathologies bronchiques chroniques.

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway inflammation. While corticosteroids (CS) are frequently prescribed during exacerbations of these conditions, their repeated use is associated with numerous side effects. The aim of this review is to synthesize the recent literature on the indications, benefits, and risks of short-term CS therapy for these two diseases. French guidelines recommend short-term CS as a first-line treatment during asthma exacerbation (0,5 to 1mg/kg/day, not exceeding 60mg/day, for at least 5 to 7 days) or as a second-line treatment for COPD exacerbation (5 days, 30 to 40mg/day). However, these recommendations are not without limitations; they are primarily based on studies conducted in hospital settings, raising questions about the generalizability of their results to primary care, and as they employ a "one size fits all" strategy, they do not take into account the phenotypic heterogeneity of different patients. Moreover, repeated short-term CS courses generate side effects that even at low doses can appear early in young asthma patients, and they can exacerbate pre-existing comorbidities in COPD patients. The concept of a threshold dose should be employed in routine practice in view of accurately assessing the risk of side effects. In the near future, it will be important to consider recently published data supporting the use of predictive biomarkers for responses to CS, particularly in COPD cases.

[The psychological burden of asthma]. / Le fardeau psychologique de l'asthme.

The experience of living with asthma varies between patients. In some cases, the psychological experience can take a central place and determine the course of asthma. Asthmatic disease can be complicated by adaption disorders that hamper the treatment, or genuine anxiety and depressive disorders that require the intervention of mental health specialists. Even more, the psychological experience can influence the intensity and frequency of the physical symptoms themselves, for example when asthma is associated with a hyperventilation syndrome worsening the functional impact and complicating the treatment. In this article, we underline the significance of the psychological experience through several clinical vignettes of patients suffering from asthma. In particular, we discuss the role of denial, or conversely identification with the status of being a patient, and the importance of the emotional experience associated with the symptoms of asthma. We highlight the relevance of therapeutic education programs as well as cognitive-behavioral therapies and psycho-corporal techniques, such as relaxation, for the psychological care of asthmatic disease. Finally, we detail how to better recognize a hyperventilation syndrome associated with asthma, how it can be approached with the patient and the treatment options. Through these examples, we illustrate the relevance of a comprehensive approach that integrates the psychological experience into the care of asthmatic disease.

Daily multidisciplinary COVID-19 meeting: Experiences from a French university hospital.

OBJECTIVES: In March 2020, the World Health Organization declared the coronavirus disease 2019 (COVID-19) a pandemic. In absence of official recommendations, implementing daily multidisciplinary team (MDT) COVID-19 meetings was urgently needed. Our aim was to describe our initial institutional standard operating procedures for implementing these meetings, and their impact on daily practice. METHODS: All consecutive patients who were hospitalized in our institution due to COVID 19, from March 31 to April 15, 2020, were included. Criteria to be presented at MDT meetings were defined as a proven COVID-19 by PCR or strongly suspected on CT scan, requiring hospitalization and treatment not included in the standard of care. Three investigators identified the patients who met the predefined criteria and compared the treatment and outcomes of patients with predefined criteria that were presented during MDT meeting with those not presented during MDT meeting. COVID-19 MDT meeting implementation and adhesion were also assessed by a hospital medical staff survey. RESULTS: In all, 318 patients with confirmed or suspected COVID-19 were examined in our hospital. Of these, 230 (87%) were hospitalized in a COVID-19 unit, 91 (40%) of whom met predefined MDT meeting criteria. Fifty (55%) patients were presented at a MDT meeting versus 41 (45%) were not. Complementary exploration and inclusion in the CorImmuno cohort were higher in MDT meeting group (respectively 35 vs. 15%, P=0.03 and 80 versus 49%, P=0.0007). Prescription of hydrocortisone hemisuccinate was higher in group of patients not presented during MDT meeting (24 vs. 51%, P=0.007). Almost half of the patients fulfilling the inclusion criteria were not presented at MDT meeting, which can be partly explained by technical software issues. CONCLUSIONS: Multidisciplinary COVID-19 meetings helped implementing a single standard of care, avoided using treatments that were untested or currently being tested, and facilitated the inclusion of patients in prospective cohorts and therapeutic trials.

Re-emergence of Corynebacterium diphtheriae.

BACKGROUND: Diphtheria is re-emerging in Europe. A total of 36 cases were reported in Europe in 2015 versus 53 cases between 2000 and 2009. PATIENTS: We report two cases of Corynebacterium diphtheriae infection in a French hospital in 2016: a cutaneous infection with negative toxin testing in a French traveller, and a respiratory diphtheria carriage with positive toxin testing in an Afghan refugee diagnosed with pulmonary tuberculosis. The vaccination history of the Afghan patient could not be retrieved.

Lymphocyte expansion after unrelated cord blood allogeneic stem cell transplantation in adults.

Limited information is available regarding the incidence and features of lymphocyte expansions after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Large granular lymphocytes (LGL) expansions have been reported after bone marrow or peripheral blood, but not after unrelated cord blood (UCB) allo-HSCT, associated with indolent clinical courses and favorable outcomes. Here, we considered 85 recipients of UCB allo-HSCT to more broadly define the impact of lymphocytosis, not limited to LGL. Sustained lymphocytosis was observed in 21 (25%) patients at a median onset of 12.6 months and with a median duration of 12 months. Immunophenotypic analysis showed predominantly CD8+ T and/or polyclonal B-cell expansions. Three patients only had monoclonal T-cell expansion. CMV reactivation was significantly more frequent in the group of patients with lymphocytosis (76% vs 28%, P=0.0001), but was not associated with survival. Conversely, 2-year disease-free survival and overall survival were significantly higher for lymphocytosis patients (85% vs 55%, P=0.01 and 85% vs 63%, P=0.03, respectively). In conclusion, expansion of T or B lymphocytes after UCB allo-HSCT in adults is not a rare event. Although occurring relatively late after transplant, this feature is predictive of a better outcome for the patients.

Neurally adjusted ventilatory assist as an alternative to pressure support ventilation in adults: a French multicentre randomized trial.

PURPOSE: Neurally adjusted ventilatory assist (NAVA) is a ventilatory mode that tailors the level of assistance delivered by the ventilator to the electromyographic activity of the diaphragm. The objective of this study was to compare NAVA and pressure support ventilation (PSV) in the early phase of weaning from mechanical ventilation. METHODS: A multicentre randomized controlled trial of 128 intubated adults recovering from acute respiratory failure was conducted in 11 intensive care units. Patients were randomly assigned to NAVA or PSV. The primary outcome was the probability of remaining in a partial ventilatory mode (either NAVA or PSV) throughout the first 48 h without any return to assist-control ventilation. Secondary outcomes included asynchrony index, ventilator-free days and mortality. RESULTS: In the NAVA and PSV groups respectively, the proportion of patients remaining in partial ventilatory mode throughout the first 48 h was 67.2 vs. 63.3 % (P = 0.66), the asynchrony index was 14.7 vs. 26.7 % (P < 0.001), the ventilator-free days at day 7 were 1.0 day [1.0-4.0] vs. 0.0 days [0.0-1.0] (P < 0.01), the ventilator-free days at day 28 were 21 days [4-25] vs. 17 days [0-23] (P = 0.12), the day-28 mortality rate was 15.0 vs. 22.7 % (P = 0.21) and the rate of use of post-extubation noninvasive mechanical ventilation was 43.5 vs. 66.6 % (P < 0.01). CONCLUSIONS: NAVA is safe and feasible over a prolonged period of time but does not increase the probability of remaining in a partial ventilatory mode. However, NAVA decreases patient-ventilator asynchrony and is associated with less frequent application of post-extubation noninvasive mechanical ventilation. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02018666.

Flow cytometric detection of dyserythropoiesis: a sensitive and powerful diagnostic tool for myelodysplastic syndromes.

Several groups have published flow cytometry scores useful for the diagnosis or prognosis of myelodysplastic syndromes (MDS), mainly based on the detection of immunophenotypic abnormalities in the maturation of granulocytic/monocytic and lymphoid lineages. As anemia is the most frequent symptom of early MDS, the aim of this study was to identify markers of dyserythropoiesis relevant for the diagnosis of MDS analyzed by selecting erythroblasts in a whole no-lysis bone marrow strategy by using a nuclear dye. This prospective study included 163 patients, including 126 with cytopenias leading to MDS suspicion and 46 controls without MDS. In a learning cohort of 53 unequivocal MDS with specific markers, there was a significant difference between the coefficients of variation of mean fluorescence intensities of CD71 and CD36 in MDS patients compared with controls. These two parameters and the hemoglobin level were used to build a RED-score strongly suggestive of MDS if ≥ 3. Using the RED-score in the whole cohort, 80% of MDS or non-MDS patients were correctly classified. When combined with the flow score described by Ogata et al., this strategy allowed to reach a very high sensitivity of 88% of patients correctly classified.