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Small-molecule nicotinamide for ex vivo expansion of umbilical cord blood.
Islam, P, Horwitz, ME
Experimental hematology. 2019;:11-15
Abstract
Umbilical cord blood transplant is an alternative graft source for patients lacking a human leukocyte antigen-matched donor; however, delayed engraftment times have historically resulted in transplant-related morbidity and mortality from complications such as infections and ineffective hematopoiesis. Recent advances in ex vivo expansion techniques have successfully augmented the initial cell dose delivered from an umbilical cord blood graft, leading to improved immune reconstitution, durable hematopoiesis, decreased transplant-related morbidity and mortality, and better outcomes. Herein we review the data for existing and developing ex vivo expansion techniques, with a focus on the preclinical and clinical data for nicotinamide-mediated cord blood expansion across both malignant and benign hematologic indications.
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2.
Effect of season of birth on cord blood IgE and IgE at birth: A systematic review and meta-analysis.
Susanto, NH, Vicendese, D, Salim, A, Lowe, AJ, Dharmage, SC, Tham, R, Lodge, C, Garden, F, Allen, K, Svanes, C, et al
Environmental research. 2017;:198-205
Abstract
BACKGROUND Elevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE. METHODS We searched Medline, Web of Science, Scopus and ProQuest Health databases, and reviewed reference lists of articles that met the inclusion criteria. All included studies measured IgE as a binary variable using various cut-off values. We performed multivariate-random-effects meta-analysis to handle an exposure with multiple categories of Season of Birth. RESULTS Our search identified 275 records and 10 had sufficient data to be included in a meta-analysis. Relative to summer, winter birth had the greatest odds of high IgE (≥ 0.1IU/ml), meta-analysis OR = 1.24 (95%CI: 1.01-1.52). A similar OR, was found for IgE ≥ 0.5 IU/ml, OR = 1.30 (95%CI: 0.99-1.71). CONCLUSIONS A winter season of birth was associated with statistically significant higher odds of elevated cord blood IgE at cut-off ≥ 0.1IU/ml but borderline at cut-off ≥ 0.5IU/ml. This winter effect is likely to be a marker for a range of other environmental exposures during specific stages of pregnancy, such as aeroallergen exposures, maternal infections and vitamin D levels. Further research is required to support our finding and to identify the exact mechanisms that lead to the winter season of birth effect on circulating IgE levels, as this may have implications for allergic disease prevention.
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3.
[Correlation between serum L-carnitine concentration and neutrophil engraftment in patients treated with cord blood transplantation].
Sano, F, Kondo, T, Matsuhashi, Y, Hyo, R, Koresawa, R, Susuki, S, Hayashi, K, Tasaka, T, Wada, H, Sugihara, T
[Rinsho ketsueki] The Japanese journal of clinical hematology. 2016;(2):165-70
Abstract
In cord blood transplantation (CBT), the amount of time elapsing until hematological engraftment has effects on the transplantation results. Carnitine deficiency has been reported to cause erythropoietin refractory anemia in chronic hemodialysis patients and thrombocytopenia or leukopenia of cirrhosis, and carnitine supplementation can improve hematopoiesis in patients with hepatic or renal failure. Patients who receive CBT may suffer from carnitine deficiency, but no studies have investigated the carnitine status of such patients. Herein, we determined the concentration of free carnitine (FC) and investigated the correlation between FC and engraftment in patients who received CBT. Twenty-three patients who received CBT at our hospital during the period from April 2013 to January 2015 were enrolled in this study. One patient was excluded because of graft failure, such that 22 patients were ultimately evaluable. FC concentrations of the patients were sequentially monitored at 4 time points (before conditioning therapy, day 0, day 7, and day 14), basic laboratory data were collected, and their correlations with engraftment were analyzed. FC concentrations of the patients were generally low (before conditioning therapy: 33.1, day 0: 43.2, day 7: 38.3, and day 14: 37.8 μmol/l). Significant inverse correlations were observed between FC concentrations and the number of days required for neutrophil engraftment on day 0 and day 14 (before conditioning therapy: P=0.15, r=-0.33, day 0: P=0.04, r=-0.43, day 7: P=0.30, r=-0.23, and day 14: P=0.01, r=-0.55). These results suggest carnitine to be an important nutrient that promotes hematopoietic recovery after CBT.
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4.
Maternal and cord blood vitamin D status and childhood infection and allergic disease: a systematic review.
Fried, DA, Rhyu, J, Odato, K, Blunt, H, Karagas, MR, Gilbert-Diamond, D
Nutrition reviews. 2016;(6):387-410
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Abstract
CONTEXT It is unclear how in utero vitamin D deficiency affects the extraskeletal health of children, despite the known risks for adverse pregnancy/birth outcomes. OBJECTIVE This systematic review seeks to assess the effect of in utero vitamin D exposure on childhood allergy and infection outcomes using the PRISMA guidelines. DATA SOURCES MEDLINE, Cochrane Library, and Web of Science databases were searched. STUDY SELECTION Literature published through April 2015 was searched for studies reporting on the association between maternal pregnancy or cord blood vitamin D status and childhood allergy and infection. DATA EXTRACTION Of 4175 articles identified, 43 studies met the inclusion criteria. They examined a wide variety of outcomes, using many different vitamin D cutoff values in their analyses. DATA SYNTHESIS For most outcomes, results were inconsistent, although there appeared to be a protective effect between higher in utero vitamin D status and childhood lower respiratory tract infection (5 of 10 studies). CONCLUSIONS More research is needed on childhood allergy and infection outcomes, and future studies should standardize outcome reporting, especially with regard to cutoff values for vitamin D concentrations. Evidence of a protective association between in utero vitamin D exposure and lower respiratory tract infection was found, while the other outcomes were either understudied or showed inconsistent results.PROSPERO registration no. CRD42013006156.
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Perinatal outcomes of prenatal probiotic and prebiotic administration: an integrative review.
VandeVusse, L, Hanson, L, Safdar, N
The Journal of perinatal & neonatal nursing. 2013;(4):288-301; quiz E1-2
Abstract
The purpose of this integrative review was to identify, critique, and synthesize the maternal and neonatal evidence on the prenatal use of probiotics and prebiotics to inform perinatal health professionals. A comprehensive literature search resulted in 37 studies of prenatal probiotics and 1 on antepartal prebiotics published from 1990 through 2011 that reported maternal, fetal, and/or neonatal outcomes. The methodologic quality of the studies reviewed was high, although investigators used different probiotic combinations and inconsistently reported perinatal clinical outcomes. The extraction of perinatal outcome variables resulted in identification of 9 maternal and 5 neonatal categories. Prenatal probiotics significantly reduced the incidence of bacterial vaginosis, increased colonization with vaginal Lactobacillus and intestinal Lactobacillus rhamnosus, altered immune markers in serum and breast milk, improved maternal glucose metabolism, and reduced the incidence of gestational diabetes and preeclampsia. Antepartally, probiotics were associated with significantly higher counts of Bifidobacterium and Lactococcus lactis (healthy intestinal flora) in neonatal stool. Prenatal prebiotics significantly increased maternal intestinal Bifidobacterium. No adverse events were reported and there was evidence of safety and tolerance of prenatal probiotics and prebiotics in the scientific investigations reviewed. It is recommended that in future investigations of prenatal probiotics researchers explicitly report maternal and neonatal outcomes.
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Thiamine deficiency following umbilical cord blood transplant.
Trueg, A, Borho, T, Srivastava, S, Kiel, P
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2013;(2):223-5
Abstract
A case of Wernicke encephalopathy (WE) in the setting of umbilical cord blood transplant is reported. The patient, originally diagnosed with Philadelphia chromosome-positive acute lymphoblastic leukemia, proceeded to an umbilical cord blood transplant. He presented with altered mental status 149 days following transplant. Prompt magnetic resonance imaging, baseline thiamine level, and immediate intravenous replacement allowed for recovery of most symptoms. Accompanying this case is a review of the known cases of WE in hematopoietic cell transplants and their causative factors. This is the first known adult case of WE independent of parenteral nutrition use in the setting of umbilical cord transplant.
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Carlecortemcel-l: an ex vivo expanded umbilical cord blood cell graft for allogeneic transplantation.
Petropoulos, D, Chan, KW
Expert opinion on biological therapy. 2009;(11):1437-44
Abstract
BACKGROUND Success of umbilical cord blood transplantation (UCBT) is mostly affected by the cell dose infused and its application is limited by the size of the recipient. For most adults and older children it is not possible to find a single UCB unit large enough for reliable engraftment. One strategy to increase the number of progenitor cells available is ex vivo expansion of the unit. The main challenge of ex vivo expansion systems is how not to deplete the self-renewing cell population by driving them into differentiation into committed progenitors. OBJECTIVE Copper modulates basic cell functions, such as survival, proliferation, and differentiation. Reduction of cellular copper in ex vivo culture conditions enabled preferential proliferation of early progenitors and increased engraftment capabilities. The result of a Phase I study of carlecortemcel-l, a product derived from ex vivo expansion of UCB progenitors in the presence of a copper chelator and early-acting cytokines, and the study design for the current pivotal study are presented. METHODS A literature review using PubMed and the investigator's brochure from the manufacturer. CONCLUSIONS Early results suggest that carlecortemcel-l infusion is safe and may be associated with favorable non-relapse mortality rates. A pivotal global study is currently being conducted to evaluate safety and efficacy of this product from centralized manufacturing facilities.