The aberrant asynchronous replication — characterizing lymphocytes of cancer patients — is erased following stem cell transplantation

<p>Abstract</p> <p>Background</p> <p>Aberrations of allelic replication timing are epigenetic markers observed in peripheral blood cells of cancer patients. The aberrant markers are non-cancer-type-specific and are accompanied by increased levels of sporadic aneuploidy. The study aimed at following the epigenetic markers and aneuploidy levels in cells of patients with haematological malignancies from diagnosis to full remission, as achieved by allogeneic stem cell transplantation (alloSCT).</p> <p>Methods</p> <p><it>TP53 </it>(a tumor suppressor gene assigned to chromosome 17), <it>AML1 </it>(a gene assigned to chromosome 21 and involved in the leukaemia-abundant 8;21 translocation) and the pericentomeric satellite sequence of chromosome 17 (<it>CEN17</it>) were used for replication timing assessments. Aneuploidy was monitored by enumerating the copy numbers of chromosomes 17 and 21. Replication timing and aneuploidy were detected cytogenetically using fluorescence <it>in situ </it>hybridization (FISH) technology applied to phytohemagglutinin (PHA)-stimulated lymphocytes.</p> <p>Results</p> <p>We show that aberrant epigenetic markers are detected in patients with hematological malignancies from the time of diagnosis through to when they are scheduled to undergo alloSCT. These aberrations are unaffected by the clinical status of the disease and are displayed both during accelerated stages as well as in remission. Yet, these markers are eradicated completely following stem cell transplantation. In contrast, the increased levels of aneuploidy (irreversible genetic alterations) displayed in blood lymphocytes at various stages of disease are not eliminated following transplantation. However, they do not elevate and remain unchanged (stable state). A demethylating anti-cancer drug, 5-azacytidine, applied in vitro to lymphocytes of patients prior to transplantation mimics the effect of transplantation: the epigenetic aberrations disappear while aneuploidy stays unchanged.</p> <p>Conclusions</p> <p>The reversible nature of the replication aberrations may serve as potential epigenetic blood markers for evaluating the success of transplant or other treatments and for long-term follow up of the patients who have overcome a hematological malignancy.</p

Implementation of a patient blood management program in an Australian private hospital orthopedic unit

Paul N Morgan,1 Patrick L Coleman,2 Cintia Mayel Martinez-Garduno,3 Anoja W Gunaratne,3 Elizabeth McInnes,3 Sandy Middleton3 1Quality Improvement Unit, The Mater Private Hospital (Sydney), St. Vincent&rsquo;s Health Australia, North Sydney, NSW, Australia; 2Dale Street Medical Specialists Pty Ltd, Brookvale, NSW, Australia; 3Nursing Research Institute, St Vincent&rsquo;s Health Australia (Sydney) and the Australian Catholic University School of Nursing, Midwifery and Paramedicine, Australian Catholic University, Sydney, NSW, Australia Background: Preoperative anemia in surgical patients has been linked to increased rates of allogeneic blood transfusion (ABT) and associated adverse patient outcomes such as prolonged ventilation in intensive care, increased length of hospital stay, and infections. We conducted a multifaceted implementation for orthopedic surgeons to improve preoperative patient assessment of anemia and iron deficiency to reduce perioperative blood transfusions. Materials and methods: Using a before-and-after study design of independent samples, we recruited a convenience sample of surgeons who performed primary total hip arthroplasty at 1 Australian private hospital. Our implementation intervention consisted of: executive support, interactive education, and peer-to-peer support to encourage adherence to the National Blood Authority&rsquo;s Patient Blood Management Program (PBMP) guidelines. We also used monthly reminders, e-learning access, and posters. Pre and post medical record audits evaluated preoperative blood tests, preoperative anemia, and number of blood units transfused between day of surgery until discharge. The primary outcome was an increase in the proportion of patients with preoperative blood tests undertaken prior to total hip arthroplasty surgery as recommended by the PBMP guidelines. Results: Audits from 239 pre- and 263 postimplementation patients from 3 surgeons were conducted. Our primary outcome showed a significantly increased proportion of patients who had all the required preoperative tests postimplementation (0% to 94.6%; P&lt;0.0001). Administration of ABT significantly decreased (pre: 9.2%, n=22; post: 2.3%, n=6; P=0.001) as well as the standard 2 blood units transfused (pre: 73%, n=16; post:17%, n=1; P=0.022). The time between preoperative tests and day of surgery increased from 16 to 20 days (P&lt;0.0001), allowing more time for physician&rsquo;s review of test results. Conclusion: Our results demonstrated successful implementation of a targeted PBMP to improve preoperative assessment to diagnose and treat anemia and/or iron deficiency prior to orthopedic surgery. This avoided unnecessary ABT and therefore mitigated potential risk to the patient. Keywords: anemia, allogeneic blood transfusion, iron deficiency, patient blood management, clinician behavior change, implementation researc

Preventing food allergy in infancy and childhood: systematic review of randomised controlled trials

BACKGROUND: This systematic review of ways to prevent immediate-onset/IgE-mediated food allergy will inform guidelines by the European Academy of Allergy and Immunology (EAACI).METHODS: The GRADE approach was used. Eleven databases were searched from 1946 to October 2019 for randomised controlled trials (and large prospective cohort studies in the case of breastfeeding). The studies included heterogeneous interventions, populations and outcomes so were summarised narratively.RESULTS: Forty-six studies examined interventions to reduce the risk of food allergy in infancy (up to one year) or early childhood. The following interventions for pregnant or breastfeeding women and/or infants may have little to no effect on preventing food allergy but the evidence is very uncertain: dietary avoidance of food allergens, vitamin supplements, fish oil, probiotics, prebiotics, synbiotics and emollients. Breastfeeding, hydrolysed formulas and avoiding cow's milk formula may not reduce the risk of cow's milk protein allergy, however temporary supplementation with cow's milk formula in the first week of life may increase the risk of cow's milk allergy. Introducing well-cooked egg, but not pasteurised raw egg, from four to six months probably reduces the risk of hen's egg allergy. Introducing regular peanut consumption into the diet of an infant at increased risk beginning from four to 11 months probably results in a large reduction in peanut allergy in countries with a high prevalence. These conclusions are based on moderate certainty evidence, from single trials in high-income countries.CONCLUSIONS: Sixty percent of the included studies were published in the last ten years, but much still remains to be understood about preventing food allergy. In particular, there is a need to validate the potential benefits of early introduction of food allergens in a wider range of populations.</p