Patient-reported outcomes in the Translational Breast Cancer Research Consortium

Members of the Translational Breast Cancer Research Consortium conducted an expert-driven literature review to identify a list of domains and to evaluate potential measures of these domains for inclusion in a list of preferred measures. Measures were included if they were easily available, free of charge, and had acceptable psychometrics based on published peer-reviewed analyses. A total of 22 domains and 52 measures were identified during the selection process. Taken together, these measures form a reliable and validated list of measurement tools that are easily available and used in multiple cancer trials to assess patient-reported outcomes in relevant patients.     

Primitive human hematopoietic cells displaying differential efflux of the rhodamine 123 dye have distinct biological activities

Human bone marrow (BM) CD34+ cells were stained with the vital dye, rhodamine 123 (Rh123), and analyzed for their biological properties based on the level of dye retention. Heterogeneous rhodamine staining is seen within the CD34+ population, and the staining patterns differ dramatically between fetal BM (FBM), adult BM (ABM) and mobilized peripheral blood (MPB). Kinetic analysis of the efflux of Rh123 from ABM CD34+ cells showed that efflux of Rh123 was most rapid from the most primitive Thy-1+ subset. The efflux of Rh123 could be inhibited by verapamil, suggesting that rhodamine efflux from primitive hematopoietic cells is primarily due to the P-glycoprotein (P-gp) pump or another intracellular transport system affected by verapamil. When four CD34+ subpopulations were plated onto SyS1 BM stromal cell cocultures after 1 to 2 weeks, only wells plated with CD34+ Thy- 1+Rh123lo (low-level Rh123 retention) or CD34+Thy-1+Rh123mid (mid-level Rh123 retention) cells maintained greater than 50% of cells in an uncommitted CD34+33- stage. CD34+Lin- (lineage-negative) cells were fractionated based on Rh123 dye staining into Rh123hi (high-level Rh123 retention), Rh123mid, and Rh123lo and deposited as single cells into long-term SyS1 BM stromal cell cultures. The Rh123mid fraction had immense early proliferative activity in vitro, but lost the ability to form cobblestone areas after 5 to 6 weeks in culture. In contrast, the Rh123lo fraction proliferated more slowly but sustained long-term in vitro hematopoiesis as evidenced by continued cobblestone area-forming cells (CAFC) activity for at least 6 weeks. The Rh123hi fraction showed a plating efficiency similar to that of the Rh123lo or Rh1123mid fractions but did not extensively proliferative in vitro and did not show evidence of CAFC activity. We predicted from these in vitro results that the Rh123lo subsets possesses long-term engrafting potential. Indeed, on transplantation into the SCID-hu bone assay, all long-term engrafting potential and multilineage differentiation potential resided within the Rh123lo-mid but not Rh123hi subset. Furthermore, human marrow subpopulations derived from chimeric sheep after in utero transplantation with CD34+Thy-1+Lin- cells were reisolated based on Rh123 staining. Again, CD34+Lin- subsets showing Rh123lo-mid had long-term growth in culture, whereas Rh123hiCD34+Lin- cells did not. These results show that, after injection of CD34+Thy- 1+Lin- cells into an in utero microenvironment, primitive CD34+ cells maintain a Rh123 phenotype that correlates with their in vitro CAFC activity. Thus, Rh123 staining is an effective way to define functional subsets of primitive hematopoietic cell populations.     

Parvovirus B19 infection and Diamond-Blackfan anaemia

It is the purpose of the study to report the frequency of parvovirus in children with a diagnosis of Diamond-Blackfan anaemia and to discuss the possible aetiological role of parvovirus in Diamond-Blackfan anaemia. We found parvovirus DNA in 3 of 11 bone marrow smears. Giant pronormoblasts showed low sensitivity (33%) and poor specificity (75%). The presence of giant pronormoblasts was associated with a very high myeloid: erythroid ratio, and may not be specific for parvovirus infection, but a feature of severely suppressed erythropoiesis. The three parvovirus-positive patients were the only children who experienced a remission, and who are free of medication. The seven surviving parvovirus-negative patients are all currently on steroid treatment.     

Protein restriction in chronic renal failure

The aim of the study was to investigate the effect of a protein restricted diet on renal function and growth of children with chronic renal failure. In a multicentre prospective study 56 children (aged 2-18 years) with chronic renal failure were randomly assigned to the protein restricted (0.8-1.1 g/kg/day) or the control group. All children were followed up by the same paediatrician and dietitian. After a follow up period of three years there was no significant difference in glomerular filtration rate between children on a protein restricted diet and children of the control group. There was no significant difference in weight with respect to height and height SD score between the protein restricted and the control group. Compliance with the protein restricted diet, as indicated by the prospective diet diaries and the serum urea:creatinine ratio, was good. This study shows that children with chronic renal failure do not benefit from a protein restricted diet.     

Homing of human cells in the fetal sheep model: modulation by antibodies activating or inhibiting very late activation antigen-4-dependent function.

The mechanisms by which intravenously (IV)-administered hematopoietic cells home to the bone marrow (BM) are poorly defined. Although insightful information has been obtained in mice, our knowledge about homing of human cells is very limited. In the present study, we investigated the importance of very late activation antigen (VLA)-4 in the early phases of lodgment of human CD34(+) progenitors into the sheep hematopoietic compartment after in utero transplantation. We have found that preincubation of donor cells with anti-VLA-4 blocking antibodies resulted in a profound reduction of human cell lodgment in the fetal BM at 24 and 48 hours after transplantation, with a corresponding increase of human cells in the peripheral circulation. Furthermore, IV infusion of the anti-VLA-4 antibody at later times (posttransplantation days 21 to 24) resulted in redistribution or mobilization of human progenitors from the BM to the peripheral blood. In an attempt to positively modulate homing, we also pretreated human donor cells with an activating antibody to beta1 integrins. This treatment resulted in increased lodgment of donor cells in the fetal liver, presumably for hemodynamic reasons, at the expense of the BM. Given previous involvement of the VLA-4/vascular cell adhesion molecule (VCAM)-1 adhesion pathway in homing and mobilization in the murine system, our present data suggest that cross-reacting ligands (likely VCAM-1) for human VLA-4 exist in sheep BM, thereby implicating conservation of molecular mechanisms of homing and mobilization across disparate species barriers. Thus, information from xenogeneic models of human hematopoiesis and specifically, the human/sheep model of in utero transplantation, may provide valuable insights into human hematopoietic transplantation biology.     

Life Satisfaction and Subsequent Physical,Behavioral, and Psychosocial Health in Older Adults

Policy Points

• Several intergovernmental organizations (Organisation for Economic Co‐operation and Development, World Health Organization, United Nations) are urging countries to use well‐being indicators (e.g., life satisfaction) in addition to traditional economic indicators when making important policy decisions.
• As the number of governments implementing this new approach grows, so does the need to continue evaluating the health and well‐being outcomes we might observe from policies aimed at improving life satisfaction.
• The results of this study suggest that life satisfaction is a valuable target for policies aiming to enhance several indicators of psychosocial well‐being, health behaviors, and physical health outcomes.

ContextSeveral intergovernmental organizations (Organisation for Economic Co‐operation and Development, World Health Organization, United Nations) are urging countries to use well‐being indicators (e.g., life satisfaction) in addition to traditional economic indicators when making important policy decisions. As the number of governments implementing this new approach grows, so does the need to continue evaluating the health and well‐being outcomes we might observe from policies aimed at improving life satisfaction.MethodsWe evaluated whether positive change in life satisfaction (between t₀;2006/2008 and t₁;2010/2012) was associated with better outcomes on 35 indicators of physical, behavioral, and psychosocial health and well‐being (in t₂;2014/2016). Data were from 12,998 participants in the University of Michigan''s Health and Retirement Study—a prospective and nationally representative cohort of US adults over age 50.FindingsParticipants with the highest (versus lowest) life satisfaction had better subsequent outcomes on some physical health indicators (lower risk of pain, physical functioning limitations, and mortality; lower number of chronic conditions; and higher self‐rated health) and health behaviors (lower risk of sleep problems and more frequent physical activity), and nearly all psychosocial indicators (higher positive affect, optimism, purpose in life, mastery, health mastery, financial mastery, and likelihood of living with spouse/partner; and lower depression, depressive symptoms, hopelessness, negative affect, perceived constraints, and loneliness) over the 4‐year follow‐up period. However, life satisfaction was not subsequently associated with many specific health conditions (i.e., diabetes, hypertension, stroke, cancer, heart disease, lung disease, arthritis, overweight/obesity, or cognitive impairment), other health behaviors (i.e., binge drinking or smoking), or frequency of contact with children, family, or friends.ConclusionsThese results suggest that life satisfaction is a valuable target for policies aiming to enhance several indicators of psychosocial well‐being, health behaviors, and physical health outcomes.     

Parastomal evisceration as an extremely rare complication of a common procedure

The creation of an abdominal stoma is a common procedure performed as part of the treatment for many conditions. Common complications include poor stoma siting, high output, skin irritation, ischaemia, retraction, parastomal hernia and prolapse. An extremely rare stoma complication is parastomal evisceration. We present a case of a 48-year-old woman who presented to us with parastomal evisceration as a late complication of a transverse colostomy. It is the second case reported as acomplication of this procedure but the first that occurred after such a long postoperative period (almost 18 months).