Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.     

Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of human bone marrow cells

Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by the k-fgf/hst oncogene, stimulates the growth of a variety of cells of mesenchymal and neuroectodermal origin. Addition of FGF-4 to human long-term bone marrow cultures increased both the cell density of the stromal layer and the number of hematopoietic colony forming cells in the cultures in a dose-dependent manner. Hematopoiesis in the stromal layer persisted for up to 8 months. Erythropoiesis was maintained for up to 4 weeks, but granulocytes were the predominant nonadherent cell type. Cultures treated with FGF had increased numbers of monocytes compared with control cultures and some CD14+, CD45+ monocytes could still be detected after 8 months of continuous culture. The addition of the growth factor increased the rate of growth of the stromal layer and appeared to delay its senescence. Subcultures made in the presence of FGF-4 had up to 10-fold increases in plating efficiency and grew as relatively uniform monolayers. These subcultures retained the capacity to support hematopoiesis for several months, while untreated subcultures, made without FGF-4, grew erratically and generally lost the capacity to support hematopoiesis within 4 to 6 weeks. The improved growth after subculture greatly enhanced the reliability of limit- dilution assays of multipotential hematopoietic stem cells that use stromal cell monolayers. The primary effect of FGF-4 appeared to be on the stromal cells of the long-term bone marrow cultures, but a direct effect on hematopoietic progenitors could not be ruled out.     

Comparative effectiveness of a bioengineered living cellular construct vs. a dehydrated human amniotic membrane allograft for the treatment of diabetic foot ulcers in a real world setting

We evaluated the comparative effectiveness of a bioengineered living cellular construct (BLCC) and a dehydrated human amnion/chorion membrane allograft (dHACM) for the treatment of diabetic foot ulcers (DFUs). Using a wound care–specific electronic medical record database, we assessed real‐world outcomes in 218 patients with 226 DFUs receiving treatment in 2014 at 99 wound care centers. The analysis included DFUs ≥1 and <25 cm² with duration <=1 year and area reduction ≤20% in 14 days prior to treatment (N=163, BLCC; N=63, dHACM). The average baseline areas and durations were 6.0 cm² and 4.4 months for BLCC and 5.2 cm² and 4.6 months for dHACM, respectively. Patients treated with dHACM had more applications compared to those treated with BLCC (median 3.0 vs. 2.0) (p=0.003). A Cox model adjusted for key covariates including area and duration found the median time to closure for BLCC was 13.3 weeks compared to 26 weeks for dHACM, and the proportion of wounds healed were significantly higher for BLCC by 12 weeks (48% vs. 28%) and 24 weeks (72% vs. 47%) (p=0.01). Treatment with a bioengineered living cellular technology increased the probability of healing by 97% compared with a dehydrated amniotic membrane (hazard ratio = 1.97 [95% confidence interval 1.17, 3.33], p=0.01).     

Treat the patient or treat the disease?

Our therapeutic goals for the treatment of ulcerative colitis and Crohn's disease are evolving. Until the last decade the goals were primarily the treatment of symptoms. Regulatory approval for ulcerative colitis therapies have been based on short-term improvements in clinical indices and, most recently, the ability to heal the colonic mucosa, whereas approval for Crohn's disease therapies have been based on reductions in the CDAI (Crohn's Disease Activity Index). Over the past decade there has been increasing evidence in favor of more 'objective' measures of biologic disease activity including biomarkers such as C-reactive protein and mucosal healing in Crohn's disease and the histologic resolution of active inflammation in ulcerative colitis. The objective changes have provided expanded therapeutic goals based on longer-term maintenance therapies with the potential to modify the chronic disease behavior and to reduce pharmacoeconomic costs (reductions in hospitalizations, surgeries and neoplasia).