MixedCandida glabrata andCandida albicans disseminated candidiasis in a heroin addict

The case of a white-heroin addict who developed disseminated candidiasis following coinfection byCandida glabrata andCandida albicans is reported. Genomic random amplified polymorphic DNA typing suggested that theCandida glabrata blood isolates originated in the oral cavity of the patient. This case strengthens the evidence thatCandida species other thanCandida albicans can be involved in the pathogenesis of disseminated candidiasis in heroin addicts.     

Serum Aspergillus galactomannan for the management of disseminated histoplasmosis in AIDS

Abstract. Disseminated histoplasmosis is an emerging infection in patients with cellular immune deficiency in non-endemic countries, caused by the migration from endemic regions and the development of travels. Diagnosis can be challenging in this context because rapid diagnostic tools such as Histoplasma antigen detection or appropriate molecular tools are generally unavailable, serology is often negative in immunosuppressed patients, and isolation of the fungus from cultures often takes several weeks. Here, we report the contribution of galactomannan serum detection for the management of an HIV-infected patient with disseminated histoplasmosis.     

Healthcare-associated mucormycosis

Mucormycosis is a severe emerging invasive fungal infection that occurs as a consequence of environmental exposure. We exhaustively reviewed all the cases of mucormycosis (European Organisation for Research and Treatment of Cancer/Mycoses Study Group 2008 criteria) attributed to healthcare procedures that occurred between 1970 and 2008. A total of 169 cases were studied (29% children, 61% male). Major underlying diseases were solid organ transplantation (24%), diabetes mellitus (22%), and severe prematurity (21%). Skin was the most common localization (57%), followed by gastrointestinal tract (15%). Culture results were available in 75% (92% positive), and results of histological examination were positive in 95%. Rhizopus was the most frequent genus (43%). Infection portal of entry included surgery and presence of medical devices such as catheters or adhesive tape. Outbreaks and clusters were related to adhesive bandages (19 cases), wooden tongue depressors (n = 5), ostomy bags (n = 2), water circuitry damage (n = 2), and adjacent building construction (n = 5). Thorough investigations are mandatory to identify healthcare-associated mucormycosis, notably in neonatology, hematological, and transplantation units.     

DROP-OUT FROM CHRONIC PAIN TREATMENT PROGRAMMES: IS RANDOMIZATION JUSTIFIED IN BIOPSYCHOSOCIAL APPROACHES?

ObjectiveTo identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management.PatientsA total of 575 patients were included in the study. Of these, 203 were randomized into 4 treatment groups: self-hypnosis/self-care; music/self-care; self-care; and psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and therefore were termed a “self-hypnosis/self-care demanders” group.MethodsSocio-demographics and behavioural data were included in the analyses. Univariates analyses, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions’ treatment) and continuers were conducted in order to select variables to include in a multivariate logistic regression.ResultsUnivariate analyses yielded 8 variables, out of 18 potential predictors for drop-out, which were eligible for inclusion in the multivariate logistic regression. The model showed that having an intermediate or high educational level protects against dropping out early or late in the pain management process. Having to wait for more than 4 months before starting the treatment increases the risk of never starting it. Being randomized increases the risk of never starting the treatment.ConclusionIn a context in which randomization is considered a “gold standard” in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.LAY ABSTRACTThe aim of this study was to identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management. A total of 575 patients were included in the study. Of these, 203 patients were randomized into 4 treatment groups: self-hypnosis/self-care; music/self-care; self-care; psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and hence formed a “self-hypnosis/self-care demanders” group. Analyses of socio-demographics and behavioural data were conducted, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions’ treatment) and continuers. Results showed that having an intermediate or high educational level protects against dropping out early or late in the management process. Having to wait for more than 4 months before starting the treatment, and being randomized, increases the risk of never starting it. Thus, in a context in which randomization is considered as a “gold standard” in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.Key words: chronic pain, non-pharmacological treatment, randomization, drop-out, loss to follow-up, attrition

Chronic pain is a complex disorder in which pain appears persistent and prolonged (> 3 months) and includes biological, psychological and socio-professional factors that undermine patients’ everyday life. Patients and healthcare providers are increasingly turning to non-pharmacological treatments, such as hypnosis and music therapy, combined with cognitive behavioural therapy (CBT) (1). The efficacy of these treatment in managing chronic pain has been demonstrated (2–4).A major problem in clinical research is drop-out, which ranges from 5% to 46%, in chronic pain management, depending on the study (5). The first issue concerns the definition of drop-out, since this varies between authors: some regard drop-out as patients ending therapy before the agreed-end-of-treatment (6), others consider it as not attending therapy sessions even though patients have agreed to attend (7). The second issue is that few clinical studies in the field of chronic pain take drop-out into account, thus generating a bias in the overall results of clinical trials investigating the efficacy of such treatments (8). The lack of studies and the disagreement regarding definitions lead to a range of results in the study of drop-out predictors in chronic pain. Some authors have highlighted that a low educational level increases the risk of dropping out from therapy (cohort study (9)), while others have shown the contrary (randomized trial (10)). The same controversy can be seen when considering age, sex and personality (systematic review (5); randomized trial (10); retrospective study (11); non-randomized trial (12)). Predictors outside of patient-related factors have mostly been studied in the mental health literature. As the management of chronic pain and mental health is relatively similar, consideration of these factors seems relevant. A meta-analysis showed that, in psychotherapy settings, the therapist expertise had an influence on drop-out. The results demonstrated that when trainees (pre-degree attainment) lead the group therapy, patients tended to be more likely to drop-out (13). Another meta-analysis showed that patients’ motivational level predicted drop-out from psychotherapy (14). A further barrier to completing treatments is the waiting period between initial contact and the effective start of the treatment (retrospective study (15)). Another retrospective study highlighted that the longer the patients in a substance abuse treatment programme had to wait until the onset of treatment (≥8 days), the more likely they were not to attend the first session of the programme (16).Given the lack of consensus, a better understanding of the profile of drop-outs and contextual risk factors, is essential in order to prevent this phenomenon, enhance treatment adherence and, consequently, ameliorate the study of treatment efficacy in chronic pain.The aim of this study was to retrospectively identify patient- and context-related factors to explain drop-out from randomized biopsychosocial-based treatment programmes.     

Matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry for fast and accurate identification of clinically relevant Aspergillus species

New Aspergillus species have recently been described with the use of multilocus sequencing in refractory cases of invasive aspergillosis. The classical phenotypic identification methods routinely used in clinical laboratories failed to identify them adequately. Some of these Aspergillus species have specific patterns of susceptibility to antifungal agents, and misidentification may lead to inappropriate therapy. We developed a matrix‐assisted laser desorption ionization time‐of‐flight (MALDI‐TOF) mass spectrometry (MS)‐based strategy to adequately identify Aspergillus species to the species level. A database including the reference spectra of 28 clinically relevant species from seven Aspergillus sections (five common and 23 unusual species) was engineered. The profiles of young and mature colonies were analysed for each reference strain, and species‐specific spectral fingerprints were identified. The performance of the database was then tested on 124 clinical and 16 environmental isolates previously characterized by partial sequencing of the β‐tubulin and calmodulin genes. One hundred and thirty‐eight isolates of 140 (98.6%) were correctly identified. Two atypical isolates could not be identified, but no isolate was misidentified (specificity: 100%). The database, including species‐specific spectral fingerprints of young and mature colonies of the reference strains, allowed identification regardless of the maturity of the clinical isolate. These results indicate that MALDI‐TOF MS is a powerful tool for rapid and accurate identification of both common and unusual species of Aspergillus. It can give better results than morphological identification in clinical laboratories.     

Differential subcellular distribution of mitoxantrone in relation to chemosensitization in two human breast cancer cell lines.

The present work investigates the relationship between cancer cell chemosensitivity and subcellular distribution, molecular interaction, and metabolism of an anticancer drug. To get insights into this relationship, we took advantage of the differential sensitivity of two breast cancer cell lines, MDA-MB-231 and MCF-7, to anthracyclines, along with the property of docosahexaenoic acid (DHA, 22:6n-3), to differentially enhance their cytotoxic activity. The fluorescent drug mitoxantrone (MTX) was used because of the possibility to study its subcellular accumulation by confocal spectral imaging (CSI). The use of CSI allowed us to obtain semiquantitative maps of four intracellular species: nuclear MTX bound to DNA, MTX oxidative metabolite in endoplasmic reticulum, cytosolic MTX, and finally, MTX in a low polarity environment characteristic of membranes. MDA-MB-231 cells were found to be more sensitive to MTX (IC50 = 18 nM) than MCF-7 cells (IC50 = 196 nM). According to fluorescence levels, the nuclear and cytosolic MTX content was higher in MCF-7 than in MDA-MB-231 cells, indicating that mechanisms other than nuclear MTX accumulation account for chemosensitivity. In the cytosol, the relative proportion of oxidized MTX was higher in MDA-MB-231 (60%) than in MCF-7 (7%) cells. DHA sensitized MDA-MB-231 (approximately 4-fold) but not MCF-7 cells to MTX and increased MTX accumulation by 1.5-fold in MDA-MB-231 cells only. The DHA-stimulated accumulation of MTX was attributed mainly to the oxidative metabolite. Antioxidant N-acetyl-L-cysteine inhibited the DHA effect on both metabolite accumulation and cell sensitization to MTX. We conclude that drug metabolism and compartmentalization are associated with cell chemosensitization, and the related cytotoxicity mechanisms may involve oxidative stress.     

N-3 and N-6 fatty acids in breast adipose tissue and relative risk of breast cancer in a case-control study in Tours, France

Experimental studies have indicated that n-3 fatty acids, including alpha-linolenic acid (18:3 n-3) and long-chain n-3 polyunsaturated fatty acids inhibit mammary tumor growth and metastasis. Earlier epidemiological studies have given inconclusive results about a potential protective effect of dietary n-3 polyunsaturated fatty acids on breast cancer risk, possibly because of methodological issues inherent to nutritional epidemiology. To evaluate the hypothesis that n-3 fatty acids protect against breast cancer, we examined the fatty acid composition in adipose tissue from 241 patients with invasive, nonmetastatic breast carcinoma and from 88 patients with benign breast disease, in a case-control study in Tours, central France. Fatty acid composition in breast adipose tissue was used as a qualitative biomarker of past dietary intake of fatty acids. Biopsies of adipose tissue were obtained at the time of surgery. Individual fatty acids were measured as a percentage of total fatty acids, using capillary gas chromatography. Unconditional logistic regression modeling was used to obtain odds ratio estimates while adjusting for age, height, menopausal status and body mass index. We found inverse associations between breast cancer-risk and n-3 fatty acid levels in breast adipose tissue. Women in the highest tertile of alpha-linolenic acid (18:3 n-3) had an odds ratio of 0.39 (95% confidence intervals [CI] = 0.19-0.78) compared to women in the lowest tertile (trend p = 0.01). In a similar way, women in the highest tertile of docosahexaenoic acid (22:6 n-3) had an odds ratio of 0.31 (95% CI = 0.13-0.75) compared to women in the lowest tertile (trend p = 0.016). Women in the highest tertile of the long-chain n-3/total n-6 ratio had an odds ratio of 0.33 (95% confidence interval = 0.17-0.66) compared to women in the lowest tertile (trend p = 0.0002). In conclusion, our data based on fatty acids levels in breast adipose tissue suggest a protective effect of n-3 fatty acids on breast cancer risk and support the hypothesis that the balance between n-3 and n-6 fatty acids plays a role in breast cancer.     

Brain function in the vegetative state

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However, this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction.     

Diet, cancer, and the lipidome.

The potential for dietary fat to interfere with the development of breast cancer by delaying its occurrence makes the identification of defined molecules a mandatory step in cancer prevention. In order to circumvent the limitations and/or bias of dietary exposure assessment tools, biomarkers of past lipid intake such as the fatty acid composition of white adipose tissue have been used. When considered separately, candidate fatty acids identified as favorable on the basis of their association with breast cancer risk have usually led to inconsistent results in animal intervention studies. This inconsistency indicates that any approach based on a single fatty acid should be abandoned for an integrated view over the complex lipid interactions which finally determines the lipidome, the lipid profile that is found in individuals. This article presents a reappraisal of the role of the lipid profile through a comprehensive reanalysis of adipose tissue fatty acid composition obtained in patients with benign or malignant breast tumors as well as in experimental animals during dietary interventions. Rather than a single fatty acid, a composite indicator combining elevated monounsaturates and low omega6/omega3 fatty acid ratio was associated with breast cancer protection. This lipidome may become the template for identifying breast cancer risk related to diet, and for designing proper dietary modifications to delay the occurrence of breast cancer, although the universality of the findings cannot be assessed from a single study.