Patient-reported outcomes in HSCT for autoimmune diseases: Considerations on behalf of the EBMT ADWP, PAC, and Nurses Group.

Background: Over the last 3 decades, hematopoietic stem cell transplantation (HSCT) has been successfully used to treat severe and refractory autoimmune diseases (AIDs). A multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists is essential to determine individual suitability for HSCT. Objective: Our aim was to observe that patient-reported outcomes (PROs) and health-related quality of life instruments can capture the unique patient perspective on disease burden and impact of treatment. Methods: Herein, we describe the basis and complexity of end points measuring patient-reported perceptions of efficacy and tolerability used in clinical practice and trials for patients with AIDs undergoing autologous HSCT. Results: PRO measures and patient-reported experience measures are key tools to evaluate the impact and extent of disease burden for patients affected by AIDs. For formal scientific assessment, it is essential that validated general instruments are used, whereas adaptations have resulted in disease-specific instruments that may help guide tailored interventions. An additional approach relates to qualitative evaluations, from carefully structured qualitative research to informal narratives, as patient stories. The patients' subjectively reported responses to HSCT may be influenced by their preprocedure expectations and investment in the HSCT journey. Conclusions: The complexity of AIDs advocates for individualized and multidisciplinary approach to positively affect the patient journey. PROs and health-related quality of life need to be collected using validated instruments in clinical practice and trials to enable robustness of data and to ensure the impact of the intervention is comprehensively assessed, addressing the main questions and needs of the involved stakeholders.

Hematopoietic stem cell transplantation for autoimmune diseases in the time of COVID-19: EBMT guidelines and recommendations.

Coronavirus disease-19 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), represents one of the biggest challenges of 21st century, threatening public health around the globe. Increasing age and presence of co-morbidities are reported risk factors for severe disease and mortality, along with autoimmune diseases (ADs) and immunosuppressive treatments such as haematopoietic stem cell transplantation (HSCT), which are also associated with adverse outcomes. We review the impact of the pandemic on specific groups of patients with neurological, rheumatological, and gastroenterological indications, along with the challenges delivering HSCT in adult and pediatric populations. Moving forward, we developed consensus-based guidelines and recommendations for best practice and quality of patient care in order to support clinicians, scientists, and their multidisciplinary teams, as well as patients and their carers. These guidelines aim to support national and international organizations related to autoimmune diseases and local clinical teams delivering HSCT. Areas of unmet need and future research questions are also highlighted. The waves of the COVID-19 pandemic are predicted to be followed by an "endemic" phase and therefore an ongoing risk within a "new normality". These recommendations reflect currently available evidence, coupled with expert opinion, and will be revised according to necessary modifications in practice.

Taste alterations and cancer treatment.

PURPOSE OF REVIEW: In this review, we explore issues on the physiology of taste and smell and we critically review recent literature of taste and smell changes and the impact on food preferences throughout the cancer treatment trajectory. RECENT FINDINGS: Subjective measurements such as validated questionnaires can be valuable for the clinical setting and many studies describe taste and smell changes by self-report. Because both smell and taste are interrelated, these subjective results are difficult to interpret. Recent studies have looked more specifically at one type of malignancy with a consistent and homogeneous treatment with chemotherapy using objective taste assessment such as electrogustometry, liquid tastants or filter paper strips. SUMMARY: Taste is a combination of different sensations: smell, texture, temperature and saliva play an important role in determining the overall flavor of food. The mechanism for taste and smell abnormalities in cancer patients treated with systemic therapies remains unclear.

Fast and accurate prediction of positive and negative urine cultures by flow cytometry.

BACKGROUND: Urinary tract infection (UTI) is a widespread infectious disease in humans. Urine culture, a huge workload in the microbiology laboratory, is still the standard diagnostic test for UTI, but most of the cultures are negative. A reliable screening method could reduce unnecessary cultures and quicken reporting of negative results. METHODS: We evaluated the usefulness of a flow cytometry (FC) screening method in the prediction of positive urine culture to reduce the number of urine cultures. The urine specimens sent to the laboratory for culture were tested with the flow cytometer Accuri C6. FC bacterial counts were compared to standard urine culture results to assess the best cut-off values. RESULTS: Two hundred nine urine samples were included, of which 79 (37.8 %) were culture positive. On comparing the culture and the FC data in the ROC curve, the FC bacterial counts of ≥10(6) bacteria/mL provided a reliable screening for bacteriuria with a sensitivity and specificity of 99 and 58 %, respectively. All negative FC results (<10(6) bacteria/mL) showed a negative predictive value of 99 % with a negative likelihood ratio of 0.02. The FC bacterial counts of ≥10(8)/mL showed a positive predictive value of 99 % with a positive likelihood ratio of 60.9. CONCLUSIONS: Counting bacteria in human urine samples by the FC is a fast, accurate and cost-effective screening method for bacteriuria. Our results showed that FC is able to rule out UTI, which can lead to a substantial reduction (36 %) of urine cultures. It also demonstrated that this method predicts positive cultures accurately.

Evaluation of Dutch guideline for just-in-time addition of plerixafor to stem cell mobilization in patients who fail with granulocyte-colony-stimulating factor.

BACKGROUND: Plerixafor in combination with granulocyte-colony-stimulating factor (G-CSF) is approved for the use of stem cell collection in patients who fail to mobilize on G-CSF. In 2009 the Stem Cell Working Party of the Dutch-Belgian Cooperative Trial group for Hematology Oncology (HOVON) composed a guideline for the use of plerixafor. According to this guideline it is recommended to add plerixafor to G-CSF in patients with circulating CD34+ cell counts of fewer than 20 × 10(6) /L on 2 consecutive days accompanied by increasing white blood cells. STUDY DESIGN AND METHODS: In this analysis we evaluated retrospectively the outcome of the use of this guideline in the Netherlands. In total 111 patients received plerixafor with a median one administration (range, one to four administrations). Of these patients 55.8% had non-Hodgkin lymphoma, 31.5% multiple myeloma, 8.1% Hodgkin lymphoma, and 4.5% nonhematologic malignancies. RESULTS: In 63.9% patients sufficient numbers of CD34+ cells were collected. In patients with multiple myeloma more successful mobilizations with plerixafor were observed compared to patients with non-Hodgkin lymphoma (71.4% vs. 61.3%). In patients with circulating CD34+ cell counts of at least 2.0 × 10(6) /L before administration of plerixafor a successful mobilization was achieved in 76.5%, and in the patients with very low (0-1 × 10(6) /L) circulating CD34+ cell counts the success rate was 44.2%. CONCLUSION: Application of the HOVON guideline on the just-in-time administration of plerixafor is effective for mobilization of hematopoietic stem cells in the majority of patients. Stem cell yield in patients with non-Hodgkin lymphoma was lower compared to patients with multiple myeloma. Also patients with very low circulating CD34+ cells before addition of plerixafor might benefit from this approach.

ZAP70 in B-CLL cells related to the expression in NK cells is a surrogate marker for mutational status.

The strongest prognostic factor in chronic B-cell lymphocytic leukemia (CLL) is the mutational status of the immunoglobulin heavy chain variable region (IGHV) genes. Determination of this mutational status is laborious and therefore not applied in routine diagnostics. A search for "surrogate markers" has been conducted over the past few years. One of the most promising surrogate markers is ZAP70, but standardization of the measurement of ZAP70 has proven to be difficult. Conventionally, ZAP70 expression in CLL cells is related to ZAP70 expression in T cells. We propose a new method in which ZAP70 expression in NK cells is used as reference (new NK-MFI method). We have measured ZAP70 expression in samples of 45 previously untreated CLL patients. ZAP70 in CLL cells related to ZAP70 in NK cells correlated better to cytogenetic risk profile and mutational status than the conventional methods. Negativity of both ZAP70 (new NK-MFI method) and CD38 resulted in a probability of 90% for mutated IGHV genes. In conclusion, ZAP70 expression in CLL cells related to ZAP70 expression in NK cells is a better surrogate marker for mutational status than the conventional T cell related methods.

ZAP70 in B-CLL cells related to the expression in NK cells is a surrogate marker for mutational status.

The strongest prognostic factor in chronic B-cell lymphocytic leukaemia (CLL) is the mutational status of the immunoglobulin heavy chain variable region (IGHV) genes. Determination of this mutational status is laborious and therefore not applied in routine diagnostics. A search for 'surrogate markers' has been conducted over the past few years. One of the most promising surrogate markers is ZAP70, but standardisation of the measurement of ZAP70 has proven to be difficult. Conventionally, ZAP70 expression in CLL cells is related to ZAP70 expression in T cells. We propose a new method in which ZAP70 expression in NK cells is used as reference (new NK-MFI method). We have measured ZAP70 expression in samples of 45 previously untreated CLL patients. ZAP70 in CLL cells related to ZAP70 in NK cells correlated better to cytogenetic risk profile and mutational status than the conventional methods. Negativity of both ZAP70 (new NK-MFI method) and CD38 resulted in a probability of 90% for mutated IGHV genes. In conclusion, ZAP70 expression in CLL cells related to ZAP70 expression in NK cells is a better surrogate marker for mutational status than the conventional T cell related methods. © 2013 Clinical Cytometry Society.

Relationship of physical fitness to prevalence and incidence of overweight among schoolchildren.

OBJECTIVES: We examined the relationship between comprehensive fitness tests and overweight using a school surveillance system in a racially diverse city in the United States. RESEARCH METHODS AND PROCEDURES: Trained physical education teachers measured weight, height, and fitness annually from 2001 to 2003. We compiled data for a cross-sectional analysis (11,845 measurements on 6297 students, 5 to 14 years of age) and a 1-year prospective analysis (4215 measurements on 2927 students not overweight at baseline, 5 to 13 years of age). Overweight was defined as a BMI > or =95th percentile (Centers for Disease Control and Prevention 2000 growth charts), and underfit was defined as failing at least one of five fitness tests: endurance run, abdominal strength, flexibility, upper body strength, and agility (Amateur Athletic Union and Fitnessgram). Associations between fitness and overweight were examined using multivariate logistic regression models, adjusting for sociodemographic status and repeated measurements over time. RESULTS: The mean number of fitness tests passed was lower among students with a BMI above the 80th percentile. Overweight incidence over 1 year was 7% and 2% for underfit and fit girls, respectively (odds ratio, 3.3; 95% confidence interval, 2.0 to 5.6). Not passing either the endurance run or upper body strength test was associated with overweight incidence in both boys and girls. After adjusting for baseline BMI, the endurance run remained a significant predictor of incident overweight among girls (odds ratio, 2.0; 95% confidence interval, 1.1 to 3.5). DISCUSSION: Findings support a cross-sectional inverse relationship between physical fitness and overweight among school-aged children. The direction of causation between fitness and overweight is not clearly established and merits further study.

Incidence and remission rates of overweight among children aged 5 to 13 years in a district-wide school surveillance system.

OBJECTIVES: To monitor annual changes in weight status, we determined incidence and remission rates of overweight among school-aged children with longitudinal school-based surveillance. METHODS: We estimated 1-year changes in weight status among students enrolled in public schools in Cambridge, Mass. Physical education teachers measured height and weight annually. Adjusted odds ratios (ORs) were estimated via multivariate logistic regression, accounting for repeated observations of individual children across years. RESULTS: The 1-year incidence of overweight was 4%, and the remission rate was 15%. Among overweight children, 85% remained overweight at a 1-year follow-up, while 18% of children at risk for overweight became overweight. Overweight incidence rates were higher among children aged 7 and 8 years than among those aged 11 to 13 years (boys: OR=1.68; 95% confidence interval [CI]=1.14, 2.47; girls: OR=1.86; 95% CI=1.25, 2.77). CONCLUSIONS: Both incidence and remission rates were higher among younger children. Children who were at risk for overweight were more likely to change their weight status than those who were already overweight. Our results support targeting overweight prevention efforts toward younger children and children at risk for overweight.

Defining and understanding healthy lifestyles choices for adolescents.

PURPOSE: To: (a) establish criteria for defining positive health behaviors and lifestyle; and (b) identify characteristics of adolescents who practice a healthy lifestyle. METHODS: Responses from a 1998 survey via questionnaire, of 1487 students, from a public high school, Cambridge, Massachusetts, were used to assess correlates of healthy lifestyle choices. Strict and broad assessments of healthy behaviors were defined for students: use of alcohol, tobacco, and illegal drugs; sexual behavior; attempted suicide. Whereas the "strict" criteria included only those adolescents who did not practice any of the behaviors in question, the broad criteria reflected experimentation and moderate risk-taking. The prevalence of positive behaviors was assessed by demographic and student characteristics. In addition, logistic regression models were created to predict determinants of teenagers' healthy lifestyles using both strict and broad definitions. RESULTS: Using strict criteria of healthy lifestyle, significant predictors were being female, born outside the United States, higher academic performance, and fewer stressful life events. Using a broad definition of a healthy lifestyle, significant predictors were being non-Caucasian, in the lower grade levels at the school, higher academic performance, and fewer stressful life events. In both models, peers' approval of risky behaviors negatively influenced teens' lifestyles, whereas parents' disapproval of risky behaviors was a positive influence. CONCLUSIONS: These results reinforce the importance of school, peer, and parent support of positive behaviors. It is important for public health workers and families to understand and define healthy lifestyles choices for adolescents.

Promoting healthy weight among elementary school children via a health report card approach.

BACKGROUND: As overweight continues to rise among children, schools seek effective and sensitive ways to engage parents in promoting healthy weight. OBJECTIVE: To evaluate a school-based health report card on the family awareness of and concern about the child weight status, plans for weight control, and preventive behaviors. DESIGN: Quasi-experimental field trial with a personalized weight and fitness health report card intervention (PI), a general-information intervention (GI), and a control group (CG). Outcomes were assessed using a postintervention telephone survey, including process and outcome measures. PARTICIPANTS: The intervention included 1396 ethnically diverse students at 4 elementary schools in an urban area. Telephone surveys were completed by 399 families from an evaluation sample of 793. Intervention Families were randomly assigned to the PI, GI, or CG and mailed intervention materials. The CG was mailed GI materials after the survey. MAIN OUTCOME MEASURES: Parent awareness of child weight status, concerns, weight-control plans, and preventive behaviors. Group effects were significantly different by the child's weight status, so results were stratified. RESULTS: Among overweight students, intervention parents were more likely to know their child's weight status (PI, 44%; GI, 41%; CG, 23%) (P =.02). The PI parents planned medical help (PI, 25%; GI, 7%; CG, 9%) (P =.004), dieting activities (PI, 19%; GI and CG, <5 cases) (P =.02) and physical activities (PI, 42%; GI, 27%; CG, 13%) (P<.001) for their overweight children. No group effect on concern or preventive behaviors was detected. Most parents of overweight children who read materials requested annual weight and health information on their child (PI, 91%; GI, 67%). CONCLUSIONS: Among overweight children, the PI was associated with increased parental awareness of their child's weight status. Although parents wanted PI for their children, more research is needed to test this approach on children's self-esteem and plans for weight control.