La nécrose médullaire, caractérisée par une nécrose des progéniteurs hématopoïétiques, des îlots adipocytaires et de la trame de réticuline, est une pathologie très rare.
Nous rapportons ...l’observation d’une patiente de 62ans admise en réanimation pour une nécrose médullaire étendue compliquant l’évolution d’une thrombocytémie essentielle associée à un choc septique sans germe retrouvé, amenant rapidement au décès dans un contexte de défaillance multiviscérale. Il s’agit, à notre connaissance, du deuxième cas rapporté dans la littérature à ce jour. Sa présentation clinique est aspécifique et associe douleurs osseuses et fièvre, et parfois un syndrome d’insuffisance médullaire. La biologie peut montrer des cytopénies diversement associées, une élévation des LDH et des phosphatases alcalines osseuses. Le diagnostic est histologique, obtenu après biopsie ostéomédullaire. La nécrose est dite étendue si elle concerne plus de 50 % du cylindre biopsique. Cette pathologie est associée dans 90 % des cas à une hémopathie maligne (notamment les leucémies) ou à une tumeur solide le plus souvent gastro-intestinale ou pulmonaire. D’autres étiologies regroupent la drépanocytose ou le syndrome catastrophique des anticorps antiphospholipides, la thrombocytémie essentielle étant exceptionnellement responsable d’une nécrose médullaire.
Toutes causes confondues, le pronostic de la nécrose médullaire étendue est généralement sombre sauf en cas de traitement précoce et intensif, notamment chez les patients drépanocytaires chez qui peut s’observer une régénération médullaire complète.
Bone marrow necrosis is a very rare condition which is characterized by a necrosis of hematopoietic progenitors, adipocytes and reticulin network.
We report a 62-year-old woman admitted to an intensive care unit for an essential thrombocytemia associated with bone marrow necrosis complicated by septic shock and progressive multi-organ failure. To our knowledge, this is the second case reported in the literature. The clinical presentation of bone marrow necrosis includes non-specific symptoms such as fever, bone pain and sometimes a clinically significant medullar insufficiency syndrome. Biology can reveal cytopenias, elevated LDH and alkaline phosphatase serum levels. The diagnosis is confirmed by bone marrow trephine biopsy. Bone marrow necrosis is classified as extensive if more than 50% of the bone marrow biopsy show necrosis. Haematological malignancies (particularly leukaemia), and solid malignant tumours (particularly gastro-intestinal or lung cancers) represent up to 90% of aetiologies and must be actively researched. Also, sickle cell disease and catastrophic anti-phospholipid syndrome must also be investigated. Essential thrombocytemia remains an exceptional cause of bone marrow necrosis.
Overall the prognosis of bone marrow necrosis is poor unless appropriate and intensive treatment, especially for sickle cell disease in which complete medullar regeneration has been observed.
Summary This study examined tap water as a source of Pseudomonas aeruginosa in a medical intensive care setting. We prospectively screened specimens of patients, tap water and hands of healthcare ...workers (HCWs) over a six-month period in a 16-bed medical intensive care unit. Molecular relatedness of P. aeruginosa strains was investigated by pulsed-field gel electrophoresis. A total of 657 tap water samples were collected from 39 faucets and 127 hands of HCWs were sampled. P. aeruginosa was found in 11.4% of 484 tap water samples taken from patients' rooms and in 5.3% of 189 other tap water samples ( P < 0.01). P. aeruginosa was isolated from 38 patients. Typing of 73 non-replicate isolates (water samples, hands of HCWs and patients) revealed 32 major DNA patterns. Eleven (52.4%) of the 21 faucets were contaminated with a patient strain, found before isolation from tap water in the corresponding room in nine cases, or from the neighbouring room in two cases. Among seven P. aeruginosa strains isolated from HCW hands, the genotype obtained was the same as that from the last patient they had touched in six cases, and in the seventh with the last tap water sample used. More than half of P. aeruginosa carriage in patients was acquired via tap water or cross-transmission. Carriage of P. aeruginosa by patients was both the source and the consequence of tap water colonisation. These results emphasise the need for studies on how to control tap water contamination.
Weaning patients with heart failure who have required mechanical ventilation remains challenging. We evaluated echocardiographic indexes and N-terminal pro-brain natriuretic peptide (NT-proBNP) as ...markers of acute cardiac dysfunction before and after spontaneous breathing trials (SBT) in such patients to assess their ability to predict subsequent successful extubation.
Forty-four patients who underwent their first SBT were prospectively included. Plasma levels of NT-proBNP and transthoracic echocardiography indices including cardiac index, E/A ratio and E/Ea ratio were recorded immediately before commencing and just before the end of SBT.
Ten patients (22.7%) failed their SBT. No significant difference was observed concerning baseline echocardiographic data and NT-proBNP level between the patients who succeeded the SBT or those that failed. Cardiac index increased significantly at end-SBT in patients who passed (3.3 3.06-3.77 vs. 3 2.68-3.3 L/min/m(2), P<0.001), whereas it remained unchanged in those that failed. E/Ea ratio (16.8 8.5-27.3 vs. 10.7 6.7-20.5, P=0.006) and NT-proBNP level (8199 3106-10949 vs. 4200 1855-7125 pg/mL, P=0.004) increased significantly in those who failed the SBT, in contrast to the weaning success group where they remained unchanged.
Neither NT-proBNP level nor the studied echocardiographic indices before SBT were able to predict SBT outcome in patients presenting with severe heart failure. Failure to increase the cardiac index and increases in both E/Ea ratio and NT-proBNP levels were seen at end-SBT in patients who failed the SBT, and may reflect failure of myocardial reserve to cope with the stress of SBT.
L’anorexie mentale est un trouble du comportement alimentaire engageant le pronostic vital par les troubles hydroélectrolytiques qu’elle provoque, ou plus rarement par une transformation gélatineuse ...de la moelle osseuse hématopoïétique (TGMO) ou une hépatite de dénutrition. Nous rapportons l’observation d’une patiente de 43 ans anorexique mentale, depuis 25 ans, admise en réanimation pour des troubles de la conscience rapidement reliés à une hépatite de dénutrition. Une TGMO était également diagnostiquée, avec notamment, la présence sur le myélogramme de travées fibroblastiques, signe cytologique orientant très fortement vers ce diagnostic. L’association chez un même patient de ces deux complications n’a jamais été rapportée dans le contexte d’une anorexie mentale.
Anorexia nervosa can be a life-threatening eating disorder when complicated with electrolyte disturbance, gelatinous transformation of the bone marrow or starvation induced acute hepatitis. We report a 43-year-old woman suffering from anorexia nervosa for more than 25 years, who was admitted in intensive care unit for a fluctuating level of consciousness related to starvation-induced acute hepatitis. Gelatinous transformation of the bone marrow was also diagnosed. Those two entities are rare and, to our knowledge, have not been previously reported jointly in anorexia nervosa.
Pompe disease (PD) is caused by a deficiency of lysosomal acid α-glucosidase resulting from mutations in the
GAA
gene. The clinical spectrum ranges from a rapidly fatal multisystemic disorder ...(classic PD, onset < 1 year) to a milder adult onset myopathy. The aims of this study were to characterize the
GAA
mutations, to establish the disease epidemiology, and to identify potential genotype-phenotype correlations in French late-onset PD patients (onset ≥ 2 years) diagnosed since the 1970s. Data were collected from the two main laboratories involved in PD diagnosis and from the French Pompe registry. Two hundred forty-six patients (130 females and 116 males) were included, with a mean age at diagnosis of 43 years. Eighty-three different mutations were identified in the
GAA
gene, among which 28 were novel. These variants were spread all over the sequence and included 42 missense (one affecting start codon), 8 nonsense, 15 frameshift, 14 splice mutations, 3 small in-frame deletions, and one large deletion. The common c.-32-13T>G mutation was detected in 151/170 index cases. Other frequent mutations included the exon 18 deletion, the c.525del, and the missense mutations c.1927G>A (p.Gly643Arg) and c.655G>A (p.Gly219Arg). Patients carrying the c.-32-13T>G mutation had an older mean age at onset than patients non-exhibiting this mutation (36 versus 25 years). Patients with the same genotype had a highly variable age at onset. We estimated the frequency of late-onset PD in France around 1/69,927 newborns. In conclusion, we characterized the French cohort of late-onset PD patients through a nationwide study covering more than 40 years.
The efficacy of enzyme replacement therapy (ERT) in patients at an advanced stage of Pompe disease has only been addressed in a few studies. Our objective was to assess the long term effects of ERT ...in a cohort of patients with severe Pompe disease.
We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT. Patients' medical records were collected and reviewed and respiratory and motor functions, before ERT initiation and upon last evaluation were compared.
Twelve patients (7 males) were identified. Median age at symptom onset was 24years IQR=15.5; 36.0. At baseline ventilation was invasive in 11 patients and noninvasive in one, with a median ventilation time of 24h IQR=21.88; 24.00 (min 20; max 24). ERT was initiated at a median age of 52.5years IQR=35.75; 66.50. Median treatment duration was 55months IQR=39.5; 81.0. During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90min and two increased their assisted walking distance, by 80 and 20m.
Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk. ERT can be initiated in these patients in order to retain their current level of independence and ability to perform daily life activities.
•The efficacy of ERT in patients at an advanced stage of Pompe disease, confined in a wheelchair and ventilator dependent, has not been proven in a randomized trial.•We identified patients from the French Pompe Registry with severe respiratory failure and permanent wheelchair use (assisted walk for a few meters was allowed) when starting ERT.•During observational period no adverse reaction to ERT was recorded, five patients (41.67%) died, three decreased their ventilation time by 30, 60 and 90minutes and two increased their assisted walking distance, by 80 and 20meters.•Some patients at a very advanced stage of Pompe disease may show a mild benefit from ERT, in terms of increased time of autonomous ventilation and of enlarged distance in assisted walk.
Immunogenicity of recombinant human acid-alpha glucosidase (rhGAA) in enzyme replacement therapy (ERT) is a safety and efficacy concern in the management of late-onset Pompe disease (LOPD). However, ...long-term effects of ERT on humoral and cellular responses to rhGAA are still poorly understood. To better understand the impact of immunogenicity of rhGAA on the efficacy of ERT, clinical data and blood samples from LOPD patients undergoing ERT for >4 years (n = 28) or untreated (n = 10) were collected and analyzed. In treated LOPD patients, anti-rhGAA antibodies peaked within the first 1000 days of ERT, while long-term exposure to rhGAA resulted in clearance of antibodies with residual production of non-neutralizing IgG. Analysis of T cell responses to rhGAA showed detectable T cell reactivity only after in vitro restimulation. Upregulation of several cytokines and chemokines was detectable in both treated and untreated LOPD subjects, while IL2 secretion was detectable only in subjects who received ERT. These results indicate that long-term ERT in LOPD patients results in a decrease in antibody titers and residual production of non-inhibitory IgGs. Immune responses to GAA following long-term ERT do not seem to affect efficacy of ERT and are consistent with an immunomodulatory effect possibly mediated by regulatory T cells.
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