Genotyping of a family with a novel deleterious DPYD mutation supports the pretherapeutic screening of DPD deficiency with dihydrouracil/uracil ratio.

Despite the growing evidence that dihydropyrimidine dehydrogenase deficiency (DPD, encoded by the DPYD gene) confers a higher risk of developing severe toxicity, most patients are not screened for DPD deficiency before fluoropyrimidine treatment. We report here the genetic and phenotypic analyses of DPD in a family related to a patient who died after a first cycle of 5-fluorouracil and in 15 additional retrospective patients having a partial DPD deficiency (as measured by plasma dihydrouracil/uracil ratio). The patient with lethal toxicity was found to be a compound heterozygote for two DPYD mutations: a novel 8-bp duplication (c.168_175dupGAATAATT, p.Phe59Ter) and c.1679T>G (Ile560Ser). The patient's dihydrouracil/uracil ratio indicates complete DPD deficiency. The novel mutation was found in two members of the patient's family. Deleterious DPYD mutations were identified in 9 out of the 15 patients. The relationship between genotype and dihydrouracil/uracil values in the 22 patients of the present study was significant (P = 0.01).

Impact of contact isolation for multidrug-resistant organisms on the occurrence of medical errors and adverse events.

UNLABELLED: Contact isolation of infected or colonised hospitalised patients is instrumental to interrupting multidrug-resistant organism (MDRO) cross-transmission. Many studies suggest an increased rate of adverse events associated with isolation. We aimed to compare isolated to non-isolated patients in intensive care units (ICUs) for the occurrence of adverse events and medical errors. METHODS: We used the large database of the Iatroref III study that included consecutive patients from three ICUs to compare the occurrence of pre-defined medical errors and adverse events among isolated vs. non-isolated patients. A subdistribution hazard regression model with careful adjustment on confounding factors was used to assess the effect of patient isolation on the occurrence of medical errors and adverse events. RESULTS: Two centres of the Iatroref III study were eligible, an 18-bed and a 10-bed ICU (nurse-to-bed ratio 2.8 and 2.5, respectively), with a total of 1,221 patients. After exclusion of the neutropenic and graft transplant patients, a total of 170 isolated patients were compared to 980 non-isolated patients. Errors in insulin administration and anticoagulant prescription were more frequent in isolated patients. Adverse events such as hypo- or hyperglycaemia, thromboembolic events, haemorrhage, and MDRO ventilator-associated pneumonia (VAP) were also more frequent with isolation. After careful adjustment of confounders, errors in anticoagulant prescription [subdistribution hazard ratio (sHR) = 1.7, p = 0.04], hypoglycaemia (sHR = 1.5, p = 0.01), hyperglycaemia (sHR = 1.5, p = 0.004), and MDRO VAP (sHR = 2.1, p = 0.001) remain more frequent in isolated patients. CONCLUSION: Contact isolation of ICU patients is associated with an increased rate of some medical errors and adverse events, including non-infectious ones.

[Severe infection following arteriotomy with Angio-Seal]. / Infection grave compliquant une angioplastie avec utilisation d'Angio-Seal((R)).

Diagnostic or interventional femoral artery catheterizations are more and more commonly practiced, so are haemostatic puncture closure devices, used to prevent bleeding complications and decrease hospital length of stay. Complications, such as infections, have been reported after using haemostatic puncture closure devices. We report the case of a female patient presenting with severe infection after Angio-Seal use: femoral artery infection with sepsis and multiple organ failure, septic embolism with embolic skin abscesses, bacterial arthritis and inferior limb necrosis. Studies comparing the infectious risk of manual compression versus haemostatic puncture closure devices are contradictory. Nevertheless, aseptic rules must be strictly observed. Indications for these devices concern only patients with high risk of hemorrhage and should be discussed for immunodepressed, diabetic, or obese patients.

[Non-fatal disseminated mucormycosis in a solid organ transplant]. / Mucormycose disséminée d'évolution favorable chez une greffée pulmonaire.

BACKGROUND: Mucormycosis is a rare fungal infection occurring most frequently in immunocompromised patients. The pathogens are filamentous fungi, order of Mucorales. Disseminated mucormycosis is a severe, life treating disease. Early diagnosis is a major determinant for prognosis, however, it remains difficult. The management consists in an early antifungal therapy using lipid formulation of amphotericin B associated with an extensive surgical debridement. Despite this therapeutic of choice, the mortality of disseminated mucormycosis remains high. OBSERVATION: We report the case of disseminated mucormycosis in a 25 years old woman 9 months after a pulmonary transplantation. The clinical presentation included pulmonary and thyroid localization and the pathogen was Absidia corymbifera. The patient survived thanks to a large surgical debridement, and an early antifungal bitherapy by lipid formulation of amphotericin B and posaconazole. CONCLUSION: The re-emergence and the high mortality of mucormycosis in solid organ transplant receiver show the necessity to find new therapeutic approaches. Posaconazole associated with liposomal amphotericin B could be an interesting option to treat disseminated mucormycosis and improve their outcome.

[Does red blood cell storage time still influence ICU survival?]. / L'âge des culots globulaires transfusés influence-t-il toujours le pronostic des patients en réanimation ?

OBJECTIVE: Few studies have shown that aged packed red blood cells (RBC) transfusion negatively influenced the outcome of ICU patients, probably related to storage lesions which could be decreased by leukodepletion of RBC. The purpose of this study was to evaluate the impact of aged leukodepleted-RBC pack, on the outcome of ICU patients. DESIGN: Retrospective, observational, cohort study in a Medical Intensive Care Unit. PATIENTS: Consecutive patients admitted during the years 2005 and 2006, and requiring a transfusion. We recorded patient's demographic data, number of RBC unit and age of each RBC, length of ICU, mortality during ICU stay. RESULTS: Five hundred and thirty-four patients were included with global mortality was 26.6%, length of stay in ICU six days (3-14) and SAPS II 48 (35-62). RBC equaling to 5.9 were transfused per patients (22.7%<14 days and 57.3%<21 days). The number of RBC was significantly higher in the dead patients group, but the rate of RBC stored less than 21 days was not different (54% versus 60%; p=0.21). In a multivariate logistic model, independent predictors of ICU death were SAPS II (OR=1.02 per point, p<0.001), number of RBC (OR=1.08 per RBC, p<0.001), length of stay in ICU (p<0.001). Similar results were obtained while introducing the age of RBC as time dependent covariates in a multivariate Cox's model. CONCLUSIONS: RBC transfused in our ICU are old. The ICU outcome is independently associated with the number of leucodepleted RBC transfused, but not with their age.

[Cardiogenic shock due to acute myocarditis complicating leptospirosis]. / Choc cardiogénique par myocardite aiguë révélant une leptospirose.

A 48 year old man was admitted to the intensive care unit with septicaemic shock associated with febrile jaundice and anuric renal failure. Within hours, he developed cardiogenic shock with multi-organ failure due to an acute myocarditis refractory to catecholamines and requiring intra-aortic balloon pumping. The diagnosis was an ictero-haemorrhagic leptospirosis, the outcome of which was finally favourable. Myocarditis is an underestimated complication of leptospirosis because it is often symptomless. The main signs are arrhythmias, conduction defects and ST-T wave abnormalities which have little clinical expression. The disease may progress and is sometimes fatal. Leptospirosis myocarditis should therefore be carefully considered because of its potential severity and its reversibility with appropriate antibiotic therapy and also the necessity of initial management in a specific infrastructure.

[Aspergillus flavus endocarditis on a native valve]. / Endocardite à Aspergillus flavus sur valve native. A propos d' un cas.

A 33 year old female had febrile aplasia following a first chemotherapy treatment for acute T lymphoid leukaemia. She was transferred to intensive care for acute respiratory distress due to bilateral pneumonia with Stenotrophomonas maltophilia septicaemic shock. After an initial improvement with antibiotic treatment, she developed multiple necrotic cutaneous lesions. A skin biopsy showed the presence of Aspergillus flavus in large quantities in the vascular lumina. Echocardiography revealed a voluminous vegetation on the mitral valve supporting aspergillus endocarditis. Despite antifungal treatment, shock and coma developed rapidly. Cerebral CT scan suggested multiple septic emboli. Within several hours, the scenario progressed towards multiorgan failure leading the death of the patient. Aspergillus endocarditis is exceptional and usually only occurs in immunosuppressed patients. The diagnosis is difficult, and the prognosis is appalling with a mortality greater than 90% despite treatment.

A simplified cytomegalovirus pp65 antigenemia assay procedure.

A simplified cytomegalovirus (CMV) pp65 antigenemia assay using a one-step erythrocyte lysis, fixation and permeabilization process was compared with a standard protocol, the CMV CINAkit (Argene Biosoft) assay. The results were comparable, both quantitatively and qualitatively. The new method saves time. It also provides flexibility because the cell suspension can be stored so that test completion can be deferred if so desired.

[What's new in vaccines against herpes simplex infections?]. / Où en sont les vaccins contre les infections à herpès simplex?

Herpes simplex viruses (HSV) can cause a variety of infections, including genital herpes. Despite effective antiviral therapy HSV infections remain a public health problem. Vaccines offer the possibility for controlling the spread and limiting HSV disease, two strategies for herpes vaccination: prophylactic immunization or therapeutic immunization. The article discusses the results of different studies, in particular, concerning recombinant vaccines, DISC vaccines and DNA vaccines.

[Allergic bronchopulmonary aspergillosis disclosing mucoviscidosis]. / Aspergillose bronchopulmonaire allergique révélatrice d'une mucoviscidose.

In predisposed patients, allergic bronchopulmonary aspergillosis (ABPA) can arise from aspergillus bronchial colonization. We report the case of a young woman who presented with a right basal pneumonia, ground glass opacities and mediastinal adenopathies on CT scan. Biological, radiological and clinical criteria, as well as an history of childhood asthma, allowed the initial diagnosis of ABPA. However, the unusual coexistence of an additional infection with Pseudomonas Aeruginosa evoked the diagnosis of cystic fibrosis, confirmed by a sweat test and genetic analysis. Under corticosteroid and antifungal therapy and antibiotics, the clinical and radiological evolution was favourable but immuno-allergic sensitisation persisted. The ABPA-cystic fibrosis association is not rare with an estimated prevalence of 2% to 11% according to previous studies. This variability is partly explained by the difficulty of the diagnosis due to confounding clinical, radiological, and biological signs between ABPA and cystic fibrosis. Many predictive development factors of ABPA in the context of cystic fibrosis have been reported, including respiratory function, personal or familial atopy, colonization with Pseudomonas Aeruginosa and age. As in non cystic fibrosis patients, the treatment requires systemic corticotherapy and itraconazole. ABPA is still often under diagnosed and should be evoked in the context of cystic fibrosis.

[Immunoallergic reaction with hepatitis induced by minocycline]. / Réaction immuno-allergique avec hépatitite induite par la minocycline.

We report the case of a 19-year old black West Indian woman who had been treated for acne for two years with oral minocycline (50 mg per day) and topical of benzoyle peroxide (5%). She was admitted for fatigue, arthralgia, myalgia and widespread pruritus. We observed several skin lesions of hyperpigmentation, biological signs of hepatitis, and significant levels of antinuclear, anti-mitochondrial and anti-smooth muscle antibodies. Minocycline was immediately stopped. Two months later, all of the biological abnormalities had disappeared but the skin lesions seemed to be irreversible. Minocycline is largely used for the treatment of acne and may induce severe immuno-allergic reactions. Several cases of induced lupus, autoimmune hepatitis, eosinophilic pneumonia, hypersensitivity syndrome, serum-sickness-like illness and Sweet's syndrome have already been described. These side effects are rare but may be life-threatening. So, minocycline should be used as a second-line treatment for acne and should be avoided in black people whom seem to be at risk of such reactions. If, despite those precautions, minocycline-induced immuno-allergic reactions occur, the treatment should be immediately stopped and never prescribed again.