Guideline development for prevention of transfusion-associated graft-versus-host disease: reduction of indications for irradiated blood components after prestorage leukodepletion of blood components

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare, commonly fatal complication of transfusion preventable by irradiation of blood units. The revision of the Dutch transfusion guideline addressed the question whether irradiation is still necessary if blood components are prestorage leukodepleted. We searched for published cases of TA-GVHD following transfusion of prestorage leukodepleted blood and through contacting haemovigilance systems. Six presumed cases were found, dating from 1998 to 2013. Four out of six patients had received one or more non-irradiated units despite recognised indications for irradiated blood components. In the countries providing information, over 50 million prestorage leukodepleted, non-irradiated, non-pathogen-reduced cellular components were transfused in a 10-year period. Potential benefits of lifting indications for irradiation were considered. These include reduced irradiation costs (euro 1.5 million annually in the Netherlands) and less donor exposure for neonates. Findings were presented in an invitational expert meeting. Recommendations linked to human leukocyte antigen similarity between donor and recipient or intra-uterine transfusion were left unchanged. Indications linked to long-lasting deep T-cell suppression were defined with durations of 6 or 12 months after end of treatment (e.g. autologous or allogeneic stem cell transplantation). Need for continued alertness to TA-GVHD and haemovigilance reporting of erroneous non-irradiated transfusions was emphasised.Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease

De-identification of primary care electronic medical records free-text data in Ontario, Canada

<p>Abstract</p> <p>Background</p> <p>Electronic medical records (EMRs) represent a potentially rich source of health information for research but the free-text in EMRs often contains identifying information. While de-identification tools have been developed for free-text, none have been developed or tested for the full range of primary care EMR data</p> <p>Methods</p> <p>We used <it>deid </it>open source de-identification software and modified it for an Ontario context for use on primary care EMR data. We developed the modified program on a training set of 1000 free-text records from one group practice and then tested it on two validation sets from a random sample of 700 free-text EMR records from 17 different physicians from 7 different practices in 5 different cities and 500 free-text records from a group practice that was in a different city than the group practice that was used for the training set. We measured the sensitivity/recall, precision, specificity, accuracy and F-measure of the modified tool against manually tagged free-text records to remove patient and physician names, locations, addresses, medical record, health card and telephone numbers.</p> <p>Results</p> <p>We found that the modified training program performed with a sensitivity of 88.3%, specificity of 91.4%, precision of 91.3%, accuracy of 89.9% and F-measure of 0.90. The validations sets had sensitivities of 86.7% and 80.2%, specificities of 91.4% and 87.7%, precisions of 91.1% and 87.4%, accuracies of 89.0% and 83.8% and F-measures of 0.89 and 0.84 for the first and second validation sets respectively.</p> <p>Conclusion</p> <p>The <it>deid </it>program can be modified to reasonably accurately de-identify free-text primary care EMR records while preserving clinical content.</p

Dynamic Cardiolipin Synthesis Is Required for CD8⁺ T Cell Immunity

Mitochondria constantly adapt to the metabolic needs of a cell. This mitochondrial plasticity is critical to T cells, which modulate metabolism depending on antigen-driven signals and environment. We show here that de novo synthesis of the mitochondrial membrane-specific lipid cardiolipin maintains CD8+ T cell function. T cells deficient for the cardiolipin-synthesizing enzyme PTPMT1 had reduced cardiolipin and responded poorly to antigen because basal cardiolipin levels were required for activation. However, neither de novo cardiolipin synthesis, nor its Tafazzin-dependent remodeling, was needed for T cell activation. In contrast, PTPMT1-dependent cardiolipin synthesis was vital when mitochondrial fitness was required, most notably during memory T cell differentiation or nutrient stress. We also found CD8+ T cell defects in a small cohort of patients with Barth syndrome, where TAFAZZIN is mutated, and in a Tafazzin-deficient mouse model. Thus, the dynamic regulation of a single mitochondrial lipid is crucial for CD8+ T cell immunity

Mitochondrial Priming by CD28

T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand. Early CD28-dependent mitochondrial engagement is needed for T cells to remodel cristae, develop SRC, and rapidly produce cytokines upon restimulation—cardinal features of protective memory T cells. Our data show that initial CD28 signals during T cell activation prime mitochondria with latent metabolic capacity that is essential for future T cell responses

Long Time to Diagnosis of Medulloblastoma in Children Is Not Associated with Decreased Survival or with Worse Neurological Outcome

International audienceBACKGROUND: The long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae. PATIENTS AND METHODS: This retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome. RESULTS: The median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31-121, range 3-457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup. CONCLUSIONS: We found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims

Potential impact of encounter patient decision aids on the patient-clinician dialogue: a qualitative study on Dutch and American medical specialists' experiences

OBJECTIVES: To examine the experiences among Dutch and American clinicians on the impact of using encounter patient decision aids (ePDAs) on their clinical practice, and subsequently to formulate recommendations for sustained ePDA use in clinical practice. DESIGN: Qualitative study using semi-structured interviews with clinicians who used 11 different ePDAs (applicable to their specialty) for 3 months after a short training. The verbatim transcribed interviews were coded with thematic analysis by six researchers via ATLAS.ti. SETTING: Nine hospitals in the Netherlands and two hospitals in the USA. PARTICIPANTS: Twenty-five clinicians were interviewed: 16 Dutch medical specialists from four different disciplines (gynaecologists, ear-nose-throat specialists, neurologists and orthopaedic surgeon), 5 American gynaecologists and 4 American gynaecology medical trainees. RESULTS: The interviews showed that the ePDA potentially impacted the patient-clinician dialogue in several ways. We identified six themes that illustrate this: that is, (1) communication style, for example, structuring the conversation; (2) the patient's role, for example, encouraging patients to ask more questions; (3) the clinician's role, for example, prompting clinicians to discuss more information; (4) workflow, for example, familiarity with the ePDA's content helped to integrate it into practice; (5) shared decision-making (SDM), for example, mixed experiences whether the ePDA contributed to SDM; and (6) content of the ePDA. Recommendations to possibly improve ePDA use based on the clinician's experiences: (1) add pictorial health information to the ePDA instead of text only and (2) instruct clinicians how to use the ePDA in a flexible (depending on their discipline and setting) and personalised way adapting the ePDA to the patients' needs (e.g., mark off irrelevant options). CONCLUSIONS: ePDAs contributed to the patient-clinician dialogue in several ways according to medical specialists. A flexible and personalised approach appeared appropriate to integrate the use of ePDAs into the clinician's workflow, and customise their use to individual patients' needs

Asthma and Chronic Obstructive Pulmonary Disease (COPD) Prevalence and Health Services Use in Ontario Metis: A Population-Based Cohort Study

INTRODUCTION: Chronic respiratory diseases cause a significant health and economic burden around the world. In Canada, Aboriginal populations are at increased risk of asthma and chronic obstructive pulmonary disease (COPD). There is little known, however, about these diseases in the Canadian Métis population, who have mixed Aboriginal and European ancestry. A population-based study was conducted to quantify asthma and COPD prevalence and health services use in the Métis population of Ontario, Canada's largest province. METHODS: The Métis Nation of Ontario Citizenship Registry was linked to provincial health administrative databases to measure and compare burden of asthma and COPD between the Métis and non-Métis populations of Ontario between 2009 and 2012. Asthma and COPD prevalence, health services use (general physician and specialist visits, emergency department visits, hospitalizations), and mortality were measured. RESULTS: Prevalences of asthma and COPD were 30% and 70% higher, respectively, in the Métis compared to the general Ontario population (p<0.001). General physician and specialist visits were significantly lower in Métis with asthma, while general physician visits for COPD were significantly higher. Emergency department visits and hospitalizations were generally higher for Métis compared to non-Métis with either disease. All-cause mortality in Métis with COPD was 1.3 times higher compared to non-Métis with COPD (p = 0.01). CONCLUSION: There is a high burden of asthma and COPD in Ontario Métis, with significant prevalence and acute health services use related to these diseases. Lower rates of physician visits suggest barriers in access to primary care services