No Evidence that CD33 rs12459419 Polymorphism Predicts Gemtuzumab Ozogamicin Response in Consolidation Treatment of Acute Myeloid Leukemia Patients: Experience of the PETHEMA Group.

Gemtuzumab ozogamicin (GO) is a conjugate of a monoclonal antibody and calicheamicin, which has been reapproved for the treatment of acute myeloid leukemia (AML). AML patients with the CD33 rs12459419 CC genotype might benefit from the addition of GO to intensive treatment in contrast to patients with CT/TT genotypes. Nevertheless, contradictory results have been reported. We sought to shed light on the prediction of GO response in AML patients with rs12459419 polymorphism who were treated with GO in the consolidation (n = 70) or reinduction (n = 20) phase. The frequency distribution of the rs12459419 polymorphism in the complete cohort of patients was 44.4% (n = 40), 50% (n = 45), and 5.6% (n = 5) for CC, CT, and TT genotypes, respectively. Regarding the patients treated with GO for consolidation, we performed a Kaplan-Meier analysis of overall survival and relapse-free survival according to the rs12459419 polymorphism (CC vs. CT/TT patients) and genetic risk using the European Leukemia Net (ELN) 2010 risk score. We also carried out a Cox regression analysis for the prediction of overall survival, with age and ELN 2010 as covariates. We found no statistical significance in the univariate or multivariate analysis. Additionally, we performed a global Kaplan-Meier analysis for the patients treated with GO for reinduction and did not find significant differences; however, our cohort was too small to draw any conclusion from this analysis. The use of GO in consolidation treatment is included in the approval of the compound; however, evidence regarding its efficacy in this setting is lacking. Rs12459419 polymorphism could help in the selection of patients who might benefit from GO. Regrettably, in our cohort, the rs12459419 polymorphism does not seem to be an adequate tool for the selection of patients who might benefit from the addition of GO in consolidation cycles.

Spontaneous Remission of Acute Myeloid Leukemia: A Case Report.

Spontaneous remissions (SRs) in acute myeloid leukemia (AML) are infrequent, poorly documented and transient. Similarly, morphological and cytogenetic complete remissions (CR) under azacitidine treatment are scarce. We report a 71-year-old man with a secondary AML arising from essential thrombocythemia (ET), who developed an SR after discontinuation of azacitidine following a respiratory infection (four courses were administered). The distinctive feature of our case is the depth of the achieved CR, documented by next-generation sequencing (NGS) techniques. We also detected persistence of molecular lesions that might already have been present in the previous ET clone. Our patient relapsed 5 months after achieving CR. We conclude that our patient showed a spontaneous remission of his AML rather than an exquisite response to azacitidine. We hypothesize that the concurrent respiratory infection, or any other unknown trigger, might have activated his immune system forcing the leukemic stem cell to enter a quiescent state through a yet unexplained mechanism.

Fault Detection of Planetary Gears Based on Signal Space Constellations.

A new method to process the vibration signal acquired by an accelerometer placed in a planetary gearbox housing is proposed, which is useful to detect potential faults. The method is based on the phenomenological model and consists of the projection of the healthy vibration signals onto an orthonormal basis. Low pass components representation and Gram-Schmidt's method are conveniently used to obtain such a basis. Thus, the measured signals can be represented by a set of scalars that provide information on the gear state. If these scalars are within a predefined range, then the gear can be diagnosed as correct; in the opposite case, it will require further evaluation. The method is validated using measured vibration signals obtained from a laboratory test bench.

Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens.

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability.

Effects of Orange Pulp Conservation Methods (Dehydrated or Ensiled Sun-Dried) on the Nutritional Value for Finishing Pigs and Implications on Potential Gaseous Emissions from Slurry.

The inclusion of orange pulp (OP) in pig diets may promote the circular economy, but drying procedures might influence its nutritional value and environmental impact. The purpose of this study was to determine the energy value and nutrient digestibility of dehydrated (DOP) and ensiled sun dried (ESDOP) orange pulp. The potential ammonia (NH3) and methane (CH4) emissions derived from slurry were also measured. Digestible energies of 14.2 and 13.2 MJ/kg DM for DOP and ESDOP, respectively, were estimated by difference after a 500 g/kg substitution of a basal diet with OPs. A high fiber digestion efficiency was observed for both OPs. Pigs fed the basal diet showed a higher intake and a greater excretion of urine N than pigs fed with OP, but fecal N excretion did not differ among diets. A higher benzoic and hippuric acid content in urine was observed in OP than in basal diet. Altogether, these findings explained a lower pH in slurry of OP diets and a reduction of potential NH3 emissions. The biochemical CH4 potential also decreased, especially with ESDOP. Overall, both OP are relevant sources of energy for pig diets. Their inclusion in feeds generate favorable changes of slurry characteristics that reduce potential NH3 and CH4 emissions.

Influence of storage time and processing on chemical composition and in vitro ruminal fermentation of olive cake.

Olive oil extraction generates olive cake (OC) that could be used in ruminant feeding. However, the chemical composition of OC is affected by multiple factors, being therefore highly variable. The objective of this study was to analyse the influence of storage time and further processing: crude, exhausted (subjected to a second oil extraction) and cyclone (obtained from a cyclone separator) on nutritive value of OC samples. Twelve samples (six crude and six exhausted) were obtained monthly from the same pond from 1 to 6 storage months, and nine samples (three crude, three exhausted and three cyclone) were obtained monthly from a different pond from 6 to 9 months storage. Chemical composition was analysed, and OC samples were fermented in vitro with sheep rumen fluid. Increasing storage time up to 6 months decreased sugars and total soluble polyphenols content but increased fibre content in OC. Dry matter effective degradability (DMED) decreased linearly (p < 0.001) by 35.9 and 45.5% as storage time augmented from 1 to 6 months for crude and exhausted OC, respectively. Crude OC had lower DMED values than exhausted OC (averaged values 0.255 and 0.294 g/g, respectively). Both potential production and rate of gas production were lower (p ≤ 0.018) in crude compared with exhausted OC, which was attributed to the high fat content of crude OC (≥86 g/kg dry matter). For samples stored longer than 6 months, cyclone had greater (p < 0.05) DMED than crude and exhausted OC (averaged values 0.207, 0.164 and 0.164 g/g, respectively). The results indicate that ruminal degradability of OC is reduced with advancing storage time, but only subtle changes were observed during the first two months. Cyclone showed greater degradability than crude and exhausted OC, but differences between crude and exhausted OC became negligible after five storage months.

Mortality after osteoporotic hip fracture: incidence, trends, and associated factors.

BACKGROUND: It is known that mortality after hip fracture increases compared to the general population; the trend in mortality is a controversial issue. The objective of this study is to examine incidence, trends, and factors associated with mortality in patients with osteoporotic hip fractures. METHODS: This is a retrospective cohort study that uses the Registry for Hospital Discharges of the National Health System of our hospital. Patients older than 45 having an osteoporotic hip fracture between 1999 and 2015 were identified. Demographic data and comorbidities were obtained. A survival analysis was performed (Cox regression and Kaplan-Meier). Incidence rate, standardized death rate (SDR), trend (Poisson regression), and risk (hazard ratio) were calculated. RESULTS: During 1999-2015, in our hospital, there were a total of 3992 patients admitted due to osteoporotic hip fracture. Out of these 3992 patients, 3109 patients (77.9%) were women with an average age of 84.47 years (SD 8.45) and 803 (22.1%) were men with an average age of 81.64 years (SD 10.08). The cumulative incidence of mortality was 69.38%. The cumulative mortality rate for 12 months was 33%. The annual mortality was 144.9/1000 patients/year. The 1-year mortality rate increased significantly by 2% per year (IRR 1.020, CI95% 1.008-1.033). The median overall survival was 886 days (CI95% 836-951). The probability of mortality density for a period of 10 years following a hip fracture was 16% for women and 25% for men (first 90 days). The SDR was 8.3 (CI95% 7.98-8.59). Variables that showed statistically significant association with mortality were aged over 75, masculine, institutionalization, mild to severe liver disease, chronic kidney disease, COPD, dementia, heart failure, diabetes, the Charlson Index > 2 , presence of vision disorders and hearing impairment, incontinence, and Downton scale. CONCLUSIONS: For the last 17 years, an increase of mortality for patients with hip fracture and a higher mortality rate in men than in women were observed. Institutionalization combined with comorbidities is associated with a higher mortality.

Variability in the Chemical Composition and In Vitro Ruminal Fermentation of Olive Cake By-Products.

The objective of this study was to determine the variability in the chemical composition and in vitro ruminal fermentation of olive cake (OC) by-products. Forty-two OC samples with different storage times (1⁻14 months) and processing (25 crude (COC), 9 exhausted (EOC) and 9 cyclone (CYOC)) were fermented in vitro with sheep ruminal fluid. Exhausted OC samples had a lower ether extract content than COC and CYOC (15.9, 110 and 157 g/kg dry matter (DM), respectively), but greater neutral detergent fiber (NDF; 645, 570 and 441 g/kg DM) and acid insoluble nitrogen (9.76, 8.10 and 8.05 g/kg DM) content. Exhausted OC had the greatest (p < 0.05) average gas production rate (AGPR), whereas the greatest fermented organic matter (FOM) was obtained for EOC and CYOC. The best single predictor of the AGPR was total sugars content (R² = 0.898), whereas NDF was the best one for FOM (R² = 0.767; p < 0.001). Statistical models using storage time as a predictor variable had lower accuracy and R² values than those from the chemical composition. In summary, the nutritive value of OC was highly dependent on its processing, but its ether extract content did not negatively affect ruminal fermentation parameters, which could be estimated from either carbohydrate composition or storage time.

Cut-Off Values of Hematologic Parameters to Predict the Number of Alpha Genes Deleted in Subjects with Deletional Alpha Thalassemia.

Most α-thalassemia cases are caused by deletions of the structural α-globin genes. The degree of microcytosis and hypochromia has been correlated with the number of affected α-globin genes, suggesting a promising role of hematologic parameters as predictive diagnostic tools. However, cut-off points for these parameters to discriminate between the different subtypes of α-thalassemia are yet to be clearly defined. Six hematologic parameters (RBC, Hb, MCV, MCH, MCHC and RDW) were evaluated in 129 cases of deletional α-thalassemia (56 heterozygous α⁺ thalassemia, 36 homozygous α⁺ thalassemia, 29 heterozygous α° thalassemia and 8 cases of Hb H disease). A good correlation between the number of deleted alpha genes and MCV (r = -0.672, p < 0.001), MCH (r = -0.788, p < 0.001) and RDW (r = 0.633, p < 0.001) was observed. The presence of an α° allele should be discarded in individuals with microcytosis without iron deficiency and normal values of Hb A2 and Hb F with MCH < 23.40 pg. Furthermore, MCH < 21.90 pg and/or MCV < 70.80 fL are strongly suggestive of the presence of one α° allele. Finally, an accurate presumptive diagnosis of Hb H disease can be made if both RDW ≥ 20% and MCH < 19 pg are seen.

Regrouping of pigs by body weight at weaning does not affect growth performance, carcass quality or uniformity at slaughter of heavy weight pigs.

We studied the influence of pen uniformity at weaning (7.5 ± 0.6 kg vs. 7.5 ± 1.2 kg body weight (BW ± SD)) and sex on growth performance during the nursery (7.5 to 27.3 kg BW) and the fattening (27.1 to 130.5 kg BW) phases and carcass quality of barrows and castrated females (CF). During the nursery phase, pigs from the more uniform pens had lower feed efficiency (P = 0.05) than pigs from the less uniform pens. Also, barrows had higher average daily feed intake (ADFI) (P < 0.05) and average daily gain (P < 0.001) and better feed efficiency (P < 0.001) than CF. During the fattening phase, initial pen uniformity did not affect growth performance of the pigs but barrows tended (P = 0.08) to have higher ADFI and worse feed efficiency than CF. Trimmed primal cut yield tended to be higher for the more uniform pigs and better for barrows than for CF (P = 0.09). It is concluded that regrouping of the pigs at weaning according to uniformity of BW did not affect growth performance or carcass quality of the pigs at slaughter. Castrated females might be used as an alternative to barrows for the production of carcasses destined to the dry-cured industry.

Managing variability in decision making in swine growing-finishing units.

BACKGROUND: Analysis of data collected from pig farms may be useful to understand factors affecting pig health and productive performance. However, obtaining these data and drawing conclusions from them can be done at different levels and presents several challenges. In the present study, information from 688 batches of growing-finishing (GF) pigs (average initial and final body weight of 19.1 and 108.5 kg respectively) from 404 GF farms integrated in 7 companies was obtained between July 2008 and July 2010 in Spain by survey. Management and facility factors associated with feed conversion ratio (FCR) and mortality were studied by multiple linear regression analysis in each single company (A to G) and in an overall database (OD). Factors studied were geographic location of the farm, trimester the pigs entered the farm, breed of sire and sex segregation in pens (BREGENSEG), use of circovirus vaccine, number of origins the pigs were obtained from, age of the farm, percentage of slatted floor, type of feeder, drinker and ventilation, number of phases and form of feed, antibiotic administration system, water source, and number and initial weight of pigs. RESULTS: In two or more companies studied and/or in OD, the trimester when pigs were placed in the farm, BREGENSEG, number of origins of the pigs, age of the farm and initial body weight were factors associated with FCR. Regarding mortality, trimester of placement, number of origins of the pigs, water source in the farm, number of pigs placed and the initial body weight were relevant factors. Age of the farm, antibiotic administration system, and water source were only provided by some of the studied companies and were not included in the OD model, however, when analyzed in particular companies these three variables had an important effect and may be variables of interest in companies that do not record them. CONCLUSIONS: Analysing data collected from farms at different levels helps better understand factors associated with productive performance of pig herds. Out of the studied factors trimester of placement and number of origins of the pigs were the most relevant factors associated with FCR and mortality.

The prevalence of hepatitis C virus infection in patients with non-Hodgkin's lymphoma.

AIM: Lymphomagenesis is a multifactorial process in which genetic, environmental and infectious factors can be involved. The aim of the present study was to assess the prevalence of hepatitis C virus (HCV) infection among patients with non-Hodgkin's lymphoma (NHL), and to compare it with that of a control group of voluntary blood donors. METHODS: All consecutive patients with a histological diagnosis of NHL from January 1996 to December 2001 were included in this prospective study. As control group for HCV infection, voluntary blood donors recruited over the same time period from the same geographical area were considered. The presence of anti-HCV antibodies was investigated by ELISA-II and RIBA-II, and viraemia (HCV RNA) was tested by using a polymerase chain reaction (PCR). HCV genotyping was also performed. RESULTS: Ninety-nine patients (mean age 48 years) with NHL were diagnosed during the study period. Histological classification of NHL was high-intermediate grade (63 patients), and low grade (36 patients). Immunophenotype distribution was type B (86 patients) and type T (13 patients). Seven of the 99 NHL patients (7%) were infected with HCV (both using serology and PCR), five of them with immunophenotype B and two with immunophenotype T. The prevalence of HCV infection according to NHL phenotype was 5.8% in B-cell NHL and 15.4% in T-cell NHL. The HCV genotype was 1b in six cases, and 3a in one. In voluntary blood donors (mean age 45 years), HCV infection was detected in 517/55 587 (0.93%). Therefore, HCV infection was more frequent in NHL patients than in controls (odds ratio = 8.1; 95% CI = 3.7-17.6). The odds ratio for the association of HCV and B-cell NHL was 6.2 (95% CI = 2.5-15.3), and for T-cell NHL 16.4 (95% CI = 3.7-72.8). CONCLUSION: The prevalence of HCV infection in patients with NHL (both B- and T-type) is higher than that observed in controls, suggesting a role of HCV in lymphoma aetiopathogenesis.

High molecular response rate and clinical correlation in patients with follicular lymphoma treated with cyclophosphamide-vincristine-prednisone plus interferon alpha 2b.

PURPOSE: The role of molecular monitoring of minimal residual disease (MRD) in low-grade non-Hodgkin's lymphoma is controversial. We have performed a prospective study of the molecular behavior of 35 patients with follicular non-Hodgkin's lymphoma who received cyclophosphamide-vincristine-prednisone chemotherapy in conjunction with IFN-alpha 2b. EXPERIMENTAL DESIGN: Bcl-2 and clonal immunoglobulin heavy chain (IgH) gene rearrangements were assayed at diagnosis by PCR in lymph node and bone marrow (BM) and sequentially after treatment. RESULTS: Molecular markers were detected in BM of 29 (83%) patients at diagnosis: Bcl-2 rearrangement in 20 patients (90% major breakpoint and 10% minor cluster) and clonal IgH rearrangement in 9 of 15 patients negative for Bcl-2. Molecular and clinical response was noted in 25 (86%) patients after induction treatment. Progression-free survival at 5 years was 78.1 +/- 8%. A correlation between clinical and molecular response was found in 24 patients with molecular markers in BM at diagnosis and >2 years of follow-up: 94% of patients with undetectable MRD showed continuous clinical remission, whereas 50% of patients who reverted back to positive molecular markers relapsed (P < 0.05). CONCLUSIONS: The rate of molecular response is high in patients treated with cyclophosphamide-vincristine-prednisone and IFN and MRD sequential analysis is useful for disease surveillance.

Deletion of sequences flanking the t(9;22) breakpoint: a secondary genetic event associated with loss of cytogenetic response to interferon in a Philadelphia-positive chronic myeloid leukaemia patient.

We present a Ph-positive chronic myeloid leukaemia patient who lost a complete cytogenetic response (CCR) of 23 months duration at the time of detection of a deletion, not previously observed, of chromosomes 9 and 22 sequences flanking the translocation breakpoint on the derivate 9 chromosome. To our knowledge, this is the first case in which a deletion at the t(9;22) breakpoint has arisen as a secondary genetic alteration produced after formation of the t(9;22) translocation. It remains to be determined whether this genetic abnormality has the same prognostic importance as when observed at diagnosis.