Low subcutaneous adipose deposits on kid carcasses reduce their commercial value. Thus, two experiments were conducted to determine how lipid supplementation can increase fattening in Alpine male kids.In experiment 1, 12 kids received individually, ad libitum a milk replacer (15 % W/V) containing 15.9 (group 1) or 27.0 % (group 2) of fat (especially tallow fat)/DM, from 1 week of age until slaughtering at 7 weeks. In experiment 2, 14 kids were given the same milk replacer (21.5 % fat/DM) until weaning at 6 weeks and from 4 weeks until slaughtering at 14 weeks of age, water, lucerne hay and concentrate were offered ad lib. Concentrate pellets were based on cereals and soyabean-oilmeal in group 3 and on the previous milk replacer powder in group 4. In experiment 1, the level of dry matter intake was higher (6 % : NS) in group 1 than in group 2, but the growth rate was not affected, 213 and 221 g/d (respectively for groups 1 and 2).Body fat of group 1 was the least developed in offals (163 vs 224 g P : NS, 89 vs 161 g P < 0.05, 147 vs 184 g P < 0.10, 13.1 vs 19.7 g P < 0.05 respectively for omental, perirenal, mesenteric and pericardic adipose tissues) and in intermuscular leg adipose tissue (55.8 vs 69.4 g P < 0.10) but there were no differences in the two groups for subcutaneous leg and sternal adipose tissues.During the first 3-week-post weaning period of experiment 2, the level of dry matter intake was lower in group 3 than in group 4 on account of the concentrate intake. In the next period, until slaughtering, the intake of concentrate was similar in the two groups but the hay intake was higher in group 3 than in group 4. Overall growth rate of this post-weaning period was lower in group 3 (185 vs 218 g/d P < 0.10). As
BackgroundChromosomal instability, as reflected by structural or copy-number changes, is a known cancer characteristic but are rarely observed in healthy tissue. Mutations in DNA repair genes disrupt the maintenance of DNA integrity and predispose to hereditary cancer syndromes.ObjectiveTo clinically characterise and genetically diagnose two reportedly unrelated patients with unique cancer syndromes, including multiorgan tumourogenesis (patient 1) and early-onset acute myeloid leukaemia (patient 2), both displaying unique peripheral blood karyotypes.MethodsGenetic analysis in patient 1 included TruSight One panel and whole-exome sequencing, while patient 2 was diagnosed by FoundationOne Heme genomic analysis; Sanger sequencing was used for mutation confirmation in both patients. Karyotype analysis was performed on peripheral blood, bone marrow and other available tissues.ResultsBoth patients were found homozygous for CHEK2 c.499G>A; p.Gly167Arg and exhibited multiple different chromosomal translocations in 30%–60% peripheral blood lymphocytes. This karyotype phenotype was not observed in other tested tissues or in an ovarian cancer patient with a different homozygous missense mutation in CHEK2 (c.1283C>T; p.Ser428Phe).ConclusionsThe multiple chromosomal translocations in patient lymphocytes highlight the role of CHK2 in DNA repair. We suggest that homozygosity for p.Gly167Arg increases patients' susceptibility to non-accurate correction of DNA breaks and possibly explains their increased susceptibility to either multiple primary tumours during their lifetime or early-onset tumourigenesis.
Introduction: Mutations of the NPM1 gene (NPM1mut) are considered a favorable prognostic marker in acute myeloid leukemia (AML). Data from a prospective randomized trial have shown that in young AML patients with NPM1mut upfront allogeneic stem cell transplantation (allo-SCT) performed in first complete remission (CR1) may lead to a significantly improved overall survival (OS) (Dohner K, Blood 2005). However, due to considerable allo-SCT-associated morbidity and mortality and a relatively favorable outcome of these patients outside the transplant setting, many physicians are reluctant to refer NPM1mut AML patients to allo-SCT in CR1. Recently, quantitative NPM1 testing has been adopted in patient selection for allo-SCT; yet, evidence to support such practice is scant. The current single-center retrospective study compared the outcome of fit NPM1mut AML patients before and after the introduction of quantitative PCR monitoring to the routine practice at the Rambam Leukemia Unit. Methods: This retrospective cohort analysis included NPM1mut AML patients who were considered fit for intensive chemotherapy. FLT3 positivity was not an exclusion criterion. The cohort incorporated patients treated between 2011-2014 whose minimal residual disease (MRD) status was not evaluated (n=31) and patients treated between 2015-2019 who underwent MRD assessment as part of their routine follow-up (n= 38). All patients (n=69) received intensive chemotherapy (the "3+7" regimen). In the former period, our practice was to recommend allo-SCT for any NPM1mut fit patient with an available donor. Starting from 2015, bone marrow samples of all patients have been monitored for MRD both post-induction and after each consolidation cycle, using quantitative PCR. Presently, only patients failing to achieve a 3-log reduction in the NPM1mut relative expression level (NPM1/ABL) after the first consolidation are recommended to proceed to allo-SCT during CR1. In case of molecular relapse identified in former MRDneg patients, the aim is to immediately perform allo-SCT in an attempt to avoid morphological relapse. Patient demographics, comorbidities, cytogentic and molecular risk factors were compared. Survival curves were calculated with and without censoring at time of SCT. Results: Comparison of the pre-MRD monitoring cohort with the MRD-evaluated cohort revealed no difference in age (53.5 years and 56.2 years, respectively), comorbidities (ischemic heart disease, insulin-dependent diabetes mellitus, chronic kidney disease grade >2, chronic obstructive pulmonary disease and cirrhosis), high risk features such as FLT3 positive status, complex karyotype or P53 positive (38.8% and 39.5%, respectively) and extramedullary involvement (3.2% and 15.8%, respectively; P=0.12). More women were treated in the earlier period (64.5% and 39.5%, respectively; P=0.053). The use of intensified induction (daunorubicin 90mg/m2 or re-induction) was significantly more prevalent in the second cohort (50%, n=19) than in the first one (12.9%, n=4). Patients were generally prescribed the daunorubicin dose of ≥60mg/m2 or similar, apart from one patient in each group who received high-dose Ara-C as induction therapy. The use of MRD quantitative monitoring allowed reducing the portion of patients transplanted in CR1 from 61% (n=19/31) to 47.3% (n=18/38). Four patients who had not been transplanted in first molecular remission were successfully transplanted at time of molecular relapse without requiring salvage chemotherapy and prior to morphological relapse. To date, these four patients are alive and in remission at a follow-up of 1,8, 17 and 26 months from relapse. The 1- and 2-year OS was identical in the two cohorts (1 year: 77.3% vs. 86.7%; 2 years: 66.3% vs 74.4%, respectively) (Fig 1a). There was no significant change without censoring at time of SCT (Fig 1b). Conclusions: The present analysis demonstrates that in clinical practice quantitative NPM1 monitoring may be safely used for precise selection of NPM1mut fit AML patients for allo-SCT. This approach may allow avoiding transplantation in patients who may have a prolonged remission outside the transplant setting, while reserving allo-SCT for the time when such patients experience molecular relapse. The use of MRD monitoring as decision making tool in the hematologist armamentarium should be evaluated in lager patient cohorts.
Background Advances in treatment for multiple myeloma (MM) patients entail a high risk for opportunistic infections such as invasive pulmonary aspergillosis (IPA). Objectives This study was conducted to describe the patient's profile, clinical manifestations, diagnosis and outcome of MM patients with IPA, in our large haemato‐oncology centre. Patients/Methods We retrospectively analysed patients with MM who underwent Broncho alveolar lavage for pneumonia at Rambam Hospital during a 13‐year period from July 2005 to February 2018. We focused on those with Aspergillus pneumonia. Results Of the 669 patients with multiple myeloma, mean age 62.6 (±7.6) years, forty‐two patients (6.2%) were diagnosed with IPA. Among them, 60% had a probable diagnosis and 40% possible. Clinical presentation was similar for IPA and other pulmonary infections. Compared to those with other pulmonary infections, IPA was more commonly diagnosed in patients with long‐standing disease (p = .00012) and among patients receiving 3 or more lines of myeloma therapies (p = .04). Thirty‐day mortality rates following diagnostic bronchoscopy did not differ between IPA and non‐IPA patients. (p = .85). Conclusions Multiple myeloma patients had an increased risk for IPA, most notably in patients with 3 or more lines of anti‐myeloma treatment and more advanced disease. This clearly emphasises the vigilance needed for IPA in these patients.
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